Neurocognitive and QoL Profiles as a Tools for Informed Decisions in Brain Metastasis Management: Analysis from A Prospective Randomized Placebo-Controlled Trial (CTRI/2022/01/039599).

Neurocognitive and QoL Profiles as a Tools for Informed Decisions in Brain Metastasis Management: Analysis from A Prospective Randomized Placebo-Controlled Trial (CTRI/2022/01/039599). | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Neurocognitive and QoL Profiles as a Tools for Informed Decisions in Brain Metastasis Management: Analysis from A Prospective Randomized Placebo-Controlled Trial (CTRI/2022/01/039599). Haripriya Parapparambil Surendran, Debnarayan Dutta, Mazhuvancherry Kesavan Unnikrishnan, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5741939/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To evaluate neurocognitive function and quality of life (QoL) scores in brain metastasis (BM) patients as potential indicators for optimizing therapeutic interventions. Methods: Neurocognitive function and QoL scores were collected from a prospective randomized trial (CTRI/2022/01/039599) involving BM patients (n=130). Neurocognitive function was assessed using the Addenbrooke's Cognitive Examination (ACE), and QoL was measured using EORTC QLQ-C30 and BN20 questionnaires prior to radiation therapy (RT). Predictors of neurocognitive decline and QoL outcomes were identified through descriptive and regression analyses to inform intervention strategies. Results: At baseline, mean ACE scores were 75.19 ± 18.67. Among patients, 60% had normal cognitive function (ACE ≥ 75), while 28.5%, 6.2%, and 5.4% exhibited mild (1 SD decline), moderate (2 SDs decline), and severe cognitive impairment (ACE < 37), respectively. Significant predictors of impairment included poor performance status (ECOG 2; OR = 52.08, p < 0.001), education below graduation (OR = 0.002, p = 0.03), hypertension (OR = 52.08, p = 0.02), and lesions in the left temporal (OR = 71.4, p = 0.04) and occipital lobes (p = 0.03). Baseline mean global QoL score was 56.5 ± 32.5, with functional domain scores ≤60 in all patients. Conclusion: At baseline, 60% of BM patients demonstrated normal cognition, while the remaining exhibited impairments, predominantly in memory, verbal fluency, and visuospatial abilities. Severe cognitive impairment correlated with poor ECOG status, lower education, hypertension, and left temporal lesions. Incorporating neurocognitive and QoL assessments into routine practice may aid in personalized intervention planning. Trial registration number: CTRI/2022/01/039599 Addenbrooke's Cognitive Examination (ACE) Brain metastases EORTC QLQ-C30 EORTC QLQ-BN20 Cognitive impairment Neurocognitive assessment Neurocognitive profiling Quality of life (QoL) Predictive factors Radiation therapy Figures Figure 1 Figure 2 Importance of the study This study provides critical insights into the neurocognitive and quality-of-life (QoL) profiles of brain metastases (BM) patients, highlighting the significance of baseline evaluations. Prior literature has identified cognitive decline and poor QoL as prevalent issues in BM patients, but this study uniquely correlates specific predictors—such as performance status, education, hypertension, and lesion location—with neurocognitive outcomes. The findings emphasize the utility of neurocognitive assessments and QoL tools in personalizing treatment strategies. Validated, brief screening tools such as the Addenbrooke's Cognitive Examination and EORTC QoL questionnaires, helped us to prioritise interventional methods to improve patient care. Tailored interventions addressing cognitive and QoL challenges could optimize treatment decisions and long-term outcomes. Future implications include integrating these assessments into standard care protocols to support informed decision-making, enhance therapeutic efficacy, and improve BM patient care. Introduction Advancements in the management of brain metastases (BM) have significantly improved outcomes and increased survival rates, prompting research focus on cognitive impairments and quality of life (QoL) related to both disease and therapy[ 1 ]. Literature on cognitive decline after radiation therapy is heterogeneous, with memory, attention, processing speed, and executive functioning identified as the most frequently impaired cognitive domains in BM[ 2 ]. BM patients experience cognitive impairments on account of BM itself, medication use, the primary cancer, and side effects of radiotherapy and chemotherapy[ 3 – 5 ]. Thorough assessment and understanding of cognitive impairments are critical because they can negatively affect informed medical decisions, choice of radiation modalities, preserving daily functioning, and QoL. Neurocognitive assessment (NCA) before treatment is also crucial for evaluating neurocognitive changes following radiation or further management of BM[ 6 ]. Despite NCA being an objective test for neurocognitive profiling of newly diagnosed BM patients, morbidity and the long duration (2 to 3 hrs) limit wider coverage. The Addenbrooke's Cognitive Examination (ACE) is brief, yet sensitive cognitive screening tool[ 7 ]. ACE is comprehensive, brief (15 to 20 minutes) and evaluates attention, orientation, memory (recall, anterograde memory, retrograde memory, and delayed recall), language, and visuospatial abilities [ 8 ]. Likewise, there is a paucity of data on the QoL in BM patients, which directly correlates with overall well-being and functional status. We assessed QoL using a combination of (a) the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and (b) the EORTC Quality of Life Questionnaire-Brain Neoplasm 20 (EORTC QLQ-BN20) in BM patients before commencing radiation therapy[ 9 , 10 ]. Materials and Methods This report is part of a prospective placebo-controlled randomized trial investigating the role of memantine in preserving neurocognitive functions during radiotherapy in BM (CTRI/2022/01/039599) and was approved by the Institutional Ethics Committee (IEC-AIMS-2021-PHARM-338). The key inclusion criteria were: either gender, 18 years and older; diagnosis of solid malignancy with BM visible on contrast-enhanced MRI (or CT for patients unable to have an MRI); sufficient fluency in English, Malayalam, or Hindi and willingness to complete the cognitive function test and the QoL questionnaires with an ECOG performance status of 0, 1, or 2. The exclusion criteria included: patients not willing to participate; psychiatric illness, drug abuse, or mental retardation (premorbid intelligence quotient < 70); history of prior cranial external beam radiotherapy; and currently using NMDA antagonists such as amantadine, ketamine, or dextromethorphan. Patients were screened by the radiation oncologist and a clinical pharmacologist during the first consultation. Baseline data were collected from the trial data. A neuropsychologist performed NCA (before treatment) using ACE which evaluates cognitive domains such as attention and orientation, memory (encompassing recall, anterograde memory, retrograde memory, and delayed recall), language, and visuospatial abilities, yielding a score from 0 to 100, with domain-specific allocations (attention and orientation (18 points), memory (35 points), fluency (14 points), language (28 points), and visuospatial skills (5 points). (Table 1 ) Table 1 Neurocognitive functions and assessments used for analysis Cognitive domains Cognitive functions Test used Basic cognition Attention Repeating words, subtractions, or backward spelling Orientation Time, place Verbal function Verbal fluency Letter and category naming test Language Naming test, comprehension (1-stage, reading, 3-stage, complex grammar), repetition (single words and phrases), reading (regular and irregular), and writing Visuospatial function Visuospatial abilities Overlapping pentagons, Wire cube, clock drawing Memory Memory, recall, ante retrograde memory, retrograde memory, delayed recall Recall test, address test, delayed recall test, and retrograde memory test. We assessed QoL using EORTC QLQ-C30, version 3, and BN20. The QLQ-C30 is a core measure designed for all patients and includes five functional scales—physical, role (daily life), emotional, cognitive, and social; three symptom scales—fatigue, nausea and vomiting, and pain; and six single-item scales—dyspnoea, insomnia, appetite loss, constipation, diarrhoea, the financial impact of the tumour and treatment, and overall quality of life. The QLQ-BN20 consists of 20 items that assess visual disorders, motor dysfunction, communication deficits, various disease symptoms (e.g., headaches and seizures), treatment-related toxic effects (e.g., hair loss), and future uncertainty. Items from both questionnaires were scaled and scored using the recommended EORTC procedures. Raw scores were transformed to a linear scale ranging from 0 to 100. Higher QLQ-C30, scores in functional domains indicate better functioning, while higher scores in symptom domains indicate more symptoms. On the other hand, lower QLQ-BN20, scores indicate fewer symptoms and better QoL. The patients themselves filled QoL questionnaires, (with help from caregivers if required) during their first few visits (before radiation therapy). Statistical analysis We conducted all statistical analyses using IBM SPSS Statistics version 26.0. Descriptive statistics were employed to assess the patient cohort's baseline demographic, clinical, treatment, cognitive, and QoL parameters. The neurocognitive status of patients was categorized based on the mean ACE score of 75.19. We classified patients with a score of 75.19 or above as having normal cognitive performance. Cognitive decline was further categorized as follows: Mild Cognitive Decline: A decline of 1 SD (18.67) from the mean ACE score of 75.19. Moderate Cognitive Decline: A decline of 2 SDs (37.34) from the mean ACE score. Severe Cognitive Impairment: Scores falling below the 2 SD decline threshold. In addition to mean ACE scores, we computed Z-scores for the ACE and its specific domains. The Z-score was calculated using the formula \(\:x-\stackrel{-}{x}∕SD\) Where \(\:\stackrel{-}{x}\:\) represents the mean score from the dataset. We performed univariate analysis to explore the relationship between predisposing factors and the four categories of cognitive status. The subsequent multinomial logistic regression analysis was performed for the variables that demonstrated significant differences (p < 0.1) in univariate analysis. Results One thirty patients prospectively enrolled in the memantine trial (CTRI/2022/01/039599) and proceeded with NCA and QoL assessment (Fig. 1 ). Participants ranged between the ages of 31 and 75 years of age at the time of assessment. The majority were right-handed (98.4%). Twenty-six patients underwent surgery before assessment. NCA and QoL were administered 2 to 3 weeks after surgery. The patient demographics, tumour, clinical and treatment characteristics are presented in Supplementary Table 1. The mean cognitive performance of study participants was found to be 75.19 ± 18.67. The neuropsychological profile of patients with BM is summarised in Table 2 . Table 2 Domain-wise cognitive performance of enrolled patients Cognitive assessments (range) Minimum Maximum Mean Score ± SD Z score ± SD ACE (0-100) 0 100 75.19 ± 18.67 0.02 ± 0.97 Orientation (0–10) 0 10 8.48 ± 2.14 0.002 ± 1.00 Attention (0–8) 0 8 6.27 ± 2.04 -0.002 ± 1.00 Memory (0–35) 0 35 23.27 ± 7.40 0.04 ± 1.00 Recall (0–3) 0 3 1.99 ± 0.96 0.002 ± 1.00 Ante retrograde memory (0–21) 0 21 14.73 ± 4.84 0.0009 ± 1.00 Retrograde memory (0–4) 0 4 3.88 ± 1.09 -0.45 ± 1.00 Delayed recall (0–7) 0 7 3.25 ± 2.36 0.003 ± 1.00 Verbal Fluency (0–14) 0 14 9.14 ± 3.23 0.0002 ± 1.00 Language (0–28) 0 28 25.03 ± 4.62 0.0003 ± 1.00 Visuospatial abilities (0–5) 0 5 2.91 ± 1.73 -1.927 ± 0.53 MMSE (0–30) 0 35 24.63 ± 5.52 -0.0009 ± 1.00 Among the study participants, 78 patients (60.0%) exhibited normal cognitive functioning with scores of 75 or higher. A cognitive decline of 1 SD was observed in 37 patients (28.5%), with scores ranging from 74 to 56. A cognitive decline of 2 standard deviations was noted in 8 patients (6.2%), with scores between 55 and 38. Severe cognitive impairment, characterized by scores below 37, was present in 7 patients (5.4%). Details are provided in Supplementary Table 2 and Fig. 2 . Poor performance status (ECOG 2) correlated with severe cognitive impairment (19%) and vice versa (ECOG 0; 4.2% severe cognitive impairment). Likewise, mild and moderate cognitive impairment and performance status were significantly correlated (p = 0.001). Patients below graduation had severe cognitive impairment (7.2%) compared to those above graduation (2.1%; p = 0.004). Additionally, hypertensive patients demonstrated greater cognitive impairment than normotensives (11.1% vs. 3.2% p = 0.03). Lesions in the left temporal lobe and left occipital lobe were also significantly associated with cognitive impairment (p-values = 0.006 and 0.03, respectively). Of those with severe cognitive impairment, 6.7% had undergone prior surgery (p = 0.002) (Table 3 ). Table 3: Univariate Analysis of Factors Associated with Cognitive Impairment Characteristics Normal cognition (>=75) Mild cognitive impairment (74-56) Moderate cognitive impairment (55-38) Severe cognitive impairment (<37) P Value Age 56 50 (66.7%) 28 (50.9%) 16 (21.3%) 21 (38.2%) 6 (8%) 2 (3.6%) 3 (4%) 4 (7.3%) 0.10 ECOG 0 1 2 40 (83.3%) 31 (50.8%) 7 (33.3%) 4 (8.3%) 24 (39.3%) 9 (42.9%) 2 (4.2%) 5 (8.2%) 1 (4.8%) 2 (4.2%) 1 (1.6%) 4 (19.0%) <0.001 Handedness Right Left 76 (59.4%) 2 (100%) 37 (28.9%) 0 (0.0%) 8 (6.3%) 0 (0.0%) 7 (5.5%) 0 (0.0%) 0.71 Employment at the time of analysis Working Not working 38 (80.6%) 49 (52.1%) 4 (11.1%) 33 (35.1%) 3 (8.3%) 5 (5.3%) 0 (0.0%) 7 (7.4%) 0.008 Education Above graduate Below graduate 38 (80.9%) 40 (48.2%) 6 (12.8%) 31 (37.3%) 2 (4.3%) 6 (7.2%) 4 (2.1%) 3 (7.2%) 0.004 Comorbidity Present Absent 33 (52.4%) 45 (67.2%) 21 (33.3%) 16 (23.9%) 4 (6.3%) 4 (6.0%) (7.9%) (3.0%) 0.29 Hypertension Present Absent 15 (41.7%) 63 (67.0%) 15 (41.7%) 22 (23.4%) 2 (5.6%) 6 (6.4%) 3 (11.1%) 4 (3.2%) 0.03 Primary site Lung Breast Others 23 (53.5%) 32 (65.3%) 23 (60.5%) 14 (32.6%) 10 (20.4%) 13 (34.2 %) 2 (4.7%) 5 (10.2%) 1 (2.6%) 4 (9.3%) 2 (4.1%) 1 (2.6%) 0.37 Type of primary Common primary Rare primary Uncommon primary 67 (59.8%) 1 (100%) 10 (58.8%) 14 (28.6%) 10 (0.0%) 13 (29.4%) 7 (6.3%) 0 (0.0%) 1 (5.9%) 6 (5.4%) 0 (0.0%) 1 (5.9%) 0.99 Metastases sites Brain only Brain and other extracranial sites 47 (58%) 31 (63.3%) 25 (30.9%) 12 (24.5%) 3 (3.7%) 5 (10.2%) 6 (7.4%) 1 (2.0%) 0.23 Presentation of metastases Metachronous Synchronous 53 (61.6%) 25 (56.8%) 20 (23.3%) 17 (38.6%) 8 (9.3%) 0 (0.0%) 5 (5.8%) 2 (4.5%) 0.08 Tumour location Right Left Medial Bilateral 14 (63.6%) 21 (58.3%) 3 (60.0%) 40 (59.7%) 8 (36.4%) 11 (30.6%) 1 (20.0%) 17 (25.4%) 0 (0.0%) 2 (5.6%) 1 (20.4%) 5 (25.4%) 0 (0.0%) 2 (5.6%) 0 (0.0%) 5 (7.5%) 0.73 Number of lesions 1 2 Multiple 22 (57.9%) 17 (68.0%) 39 (59.1%) 13 (34.2%) 7 (28.0%) 17 (25.8%) 3 (7.9%) 0 (0.0%) 4 (6.1%) 0 (0.0%) 1 (4.0%) 6 (9.1%) 0.36 RPA Class Class 1 Class 2 47 (75.8%) 31 (45.6%) 12 (19.4%) 25 (36.8%) 1 (1.6%) 7 (10.3%) 2 (3.2%) 5 (7.4%) 0.004 Location of lesion Brain stem No Yes 67 (60.9%) 11 (55.0%) 32 (29.1%) 5 (25.0%) 6 (5.5%) 2 (10.0%) 5 (4.5%) 2 (10.0%) 0.63 Right frontal No Yes 47 (61.0%) 31 (59.6%) 23 (29.9%) 13 (25.0%) 3 (3.9%) 5 (9.6%) 4 (5.2%) 3 (5.8%) 0.58 Left frontal No Yes 50 (60.2%) 27 (58.7%) 24 (28.9%) 13 (28.3%) 6 (7.2%) 2 (4.3%) 3 (3.6%) 4 (8.7%) 0.61 Medial temporal No Yes 69 (61.6%) 9 (50.0%) 31 (27.7%) 6 (33.3%) 7 (6.3%) 1 (5.6%) 5 (4.5%) 2 (11.1%) 0.61 Near to hippocampus No Yes 70 (61.4%) 8 (50.0%) 35 (28.1%) 5 (31.3%) 7 (6.1%) 1 (6.3%) 5 (4.4%) 2 (12.5%) 0.55 Right temporal No Yes 65 (59.1%) 13 (65.0%) 33 (30.0%) 4 (20.0%) 7 (6.4%) 1 (5.0%) 5 (4.5%) 2 (10.0%) 0.64 Left temporal No Yes 62 (61.4%) 16 (55.2%) 32 (31.7%) 5 (17.2%) 5 (5.0%) 3 (10.3%) 2 (2.0%) 5 (17.2%) 0.006 Right parietal No Yes 58 (62.4%) 20 (54.1%) 26 (28.0%) 11 (29.7%) 6 (6.5%) 2 (5.4%) 3 (3.2%) 4 (10.8%) 0.36 Left parietal No Yes 49 (59.8%) 29 (60.4%) 22 (26.8%) 15 (31.3%) 7 (8.5%) 1 (2.1%) 4 (4.9%) 3 (6.3%) 0.50 Right occipital No Yes 58 (59.4%) 20 (60.7%) 32 (31.7%) 5 (17.9%) 6 (5.9%) 2 (7.1%) 3 (3.0%) 4 (14.3%) 0.08 Left occipital No Yes 61 (62.2%) 16 (51.6%) 30 (30.6%) 7 (22.6%) 3 (3.1%) 5 (16.1%) 4 (4.1%) 3 (9.7%) 0.03 Right cerebellum No Yes 51 (57.3%) 26 (65.0%) 27 (30.3%) 10 (25.0%) 6 (6.7%) 2 (5.0%) 5 (5.6%) 2 (5.05%) 0.87 Left cerebellum No Yes 43 (56.6%) 34 (64.2%) 26 (34.2%) 11 (20.8%) 3 (3.9%) 5 (9.4%) 4 (5.3%) 3 (5.7%) 0.28 Prior surgery Not done Done 67 (64.4%) 11 (42.3%) 22 (21.2%) 15 (57.7%) 8 (7.7%) 0 (0.0%) 8 (6.7%) 0 (0.0%) 0.002 Prior chemotherapy Not done Done 26 (57.8%) 52 (61.2%) 17 (37.8%) 20 (23.5%) 0 (0.0%) 8 (9.4%) 2 (4.4%) 5 (5.9%) 0.09 Steroid at the time of analysis No Yes 36 (60.0%) 42 (60.0%) 19 (31.7%) 18 (25.7%) 3 (5.0%) 5 (7.1%) 2 (3.3%) 5 (7.1%) 0.67 We conducted multinomial logistic regression on variables with a p < 0.1 in the univariate analysis (ECOG, employment, education, hypertension, metastases, RPA class, left temporal lobe lesions and bilateral occipital lobes, prior surgery/ chemotherapy). Risk for severe cognitive impairment was significantly lower in patients with above-graduate education (OR = 0.002, 95% CI: 0.57 to 0.73; p = 0.03). Hypertension and lesions in the left temporal lobe significantly increased risk of cognitive impairment, with OR = 52.08 (95% CI: 1.88 to 1441.3), p = 0.02, and OR = 71.40 (95% CI: 1.16 to 4393.2), p = 0.04, respectively. (Table 4 ) Table 4: Multinomial logistic regression analysis to determine the relationship between functional outcomes and demographic and clinical predictors. Cognitive dysfunctional status Predisposing factors Odds ratio Lower bound-upper bound P value Mild cognitive impairment Employment Working Not working 0.22 1 0.04 to 1.18 0.07 ECOG 0 1 2 0.05 0.62 1 to 0.36 0.14 to 2.60 0.003 0.51 Prior surgery Done Not done 1 0.09 0.02 to 0.41 0.002 Severe cognitive impairment Education Above graduate Below graduate 0.002 1 0.57 to 0.73 0.03 Hypertension Present Absent 52.08 1 1.88 to 1441.3 0.02 Left temporal Present Absent 71.40 1 1.16 to 4393.2 0.04 130 patients filled out the baseline QoL questionnaire (only 115 patients (88.4%) completed the questionnaire independently, 15 patients (11.5%) required assistance) (see supplementary Table 3) Global QoL score (56.5 ± 32.5) indicated a “somewhat bad quality of life”. All functional scales (physical, daily life, emotional, social, and cognitive) scores were below 60. Except for gastrointestinal symptoms, all symptom scores were elevated in BM. The BN-20 domain scores were not significantly elevated in our population. Discussion This prospective study offers important insights into the neurocognitive functioning of BM patients before radiation therapy. Most participants demonstrated normal cognitive performance, (ACE score > 75) before treatment. However, the cognitive deficit was significant in 28% and 6.2% of patients with 1 and 2 SD decline respectively. A smaller group (5.4%) had severe cognitive impairment (ACE scores < 37) Memory, (particularly ante retrograde memory, delayed recall), verbal fluency, and visuospatial abilities, were the most affected. There was significant variability in cognitive functioning within the cohort, necessitating comprehensive neurocognitive assessment before initiating treatment. The above results align with previous studies that report 53–67% exhibiting cognitive impairments on at least one cognitive test before radiotherapy[ 11 , 12 ]. However, 60% of patients in our study demonstrated normal cognitive functioning prior to treatment possibly on account of higher level of education (all above elementary school) and a reasonable performance status score below ECOG 2. In contrast, other reports show cognitive impairments in up to 79% BM patients prior to treatment. Differences in performance status and educational level may influence baseline cognitive dysfunction [ 13 ]. Poor performance status correlated with significant cognitive impairment (ECOG 2 in 19% vs ECOG 0 in 4.2% p < 0.001). This aligns with previous findings showing a strong correlation between cognitive function and performance status. For instance, Handing et al. (2020) reported that better cognitive scores, particularly on the Digit Symbol Substitution Task, were associated with improved physical function[ 14 ]. Similarly, cognitive screening tools like the modified Telephone Interview for Cognitive Status (mTICS) have been shown to predict daily functioning in older adults with mild cognitive impairment (Dixon et al., 2022)[ 15 ]. Additionally, Krayn-Deckel et al. (2022) found that cognitive impairment negatively impacted manual skills in hospitalized individuals, reinforcing the importance of physical and daily functioning as a predictor of cognitive function [ 16 ]. Left temporal lobe is critical for memory functions, with lesions signifying cognitive impairment, which align with our results. [OR = 71.4 (1.16 to 4393.2), p = 0.04]. Specifically, lesions in the hippocampus and parahippocampal gyrus in the left temporal lobe cause significant memory impairments (Schmidbauer et al., 2022; Teplyshova & Shalimanova, 2023)[ 17 , 18 ]. Additionally, activation of the left mesiotemporal structures has been positively correlated with better memory encoding and retrieval (Schmidbauer et al., 2022)[ 19 ]. Lesions in the left occipital lobe, integral to visuospatial processing, were also significantly associated with cognitive impairment (p = 0.03). Damage to this region can impair spatial awareness and visual memory, further supporting the importance of these brain regions in overall cognitive function[ 20 ]. Hypertensive patients showed greater cognitive decline (11.1% vs. 3.2%, p = 0.03) than normotensives, which aligns with previous reports. A systematic review found that approximately 37.6% of patients with hypertension experience cognitive impairment (Xie et al., 2024)[ 21 ]. Prevalence of cognitive impairment among hypertensive patients have reached up to 43.6% (Suvvari, 2023)[ 22 ]. z-scores (index of overall neurocognition) of our cohorts were different from similar reports involving other populations. Recall, delayed recall and verbal fluency scores were lower than our scores in reports from previous studies. However, attention scores were similar across diverse populations, including our own[ 11 , 23 – 26 ]. (See Table 5 .) Table 5 Neurocognitive Profiles in Brain Metastases Patients Across Different studies Cognitive domain First Author Country Year Sample size Test used Z score ± SD Recall Chang EL USA 2009 58 HVLT-R IG: -1.1 ± 1.5 CG: -0.8 ± 1.5 Westover USA 2020 50 HVLT-R -0.42 ± 1.32 Brown USA 2020 518 HVLT-R IG: -1.2 ± 1.2 CG: -1.3 ± 1.2 Present study India 2024 130 ACE 0.002 ± 1.00 Delayed recall Chang EL USA 2009 58 HVLT-DR IG: -1.3 ± 1.7 CG: -0.7 ± 1.3 Brown USA 2017 111 + 102 HVLT-DR IG: -1.3 ± 1.8 CG: -1.6 ± 1.7 Brown USA 2018 98 + 96 HVLT-DR IG: -1.5 ± 1.5 CG: -1.6 ± 1.5 Westover USA 2020 50 HVLT-DR -0.67 ± 1.37 Brown USA 2020 518 HVLT-DR IG: 1.2 ± 1.6 CG: 1.1 ± 1.3 Present study India 2024 130 ACE 0.003 ± 1.00 Attention Chang EL USA 2009 58 TMT-A IG: -2.15 ± 3.3 CG: -1.1 ± 1.9 TMT-B IG: -2.8 ± 3.3 CG: -2.4 ± 3.9 Brown USA 2017 111 + 102 TMT-A IG: -1.0 ± 1.2 CG: -1.1 ± 1.2 TMT-B IG: -2.8 ± 4.3 CG: -3.2 ± 4.3 Brown USA 2018 98 + 96 TMT-A IG: -2.2 ± 3.0 CG: -1.7 ± 3.1 TMT-B IG: -3.0 ± 3.4 CG: -2.8 ± 3.3 Westover USA 2020 50 TMT-A -1.26 ± 1.34 TMT-B -0.70 ± 0.98 Present study India 2024 130 ACE -0.002 ± 1.00 Verbal fluency Chang EL USA 2009 58 MAE-COWA IG: -0.2 ± 1.2 CG: -0.1 ± 1.2 Brown USA 2017 111 + 102 COWAT IG: -1.0 ± 1.2 CG: -1.1 ± 1.2 Westover USA 2020 50 COWAT -0.86 ± 1.15 Brown USA 2020 518 COWAT IG: -0.8 ± 1.2 CG: -0.8 ± 1.1 Present study India 2024 130 ACE 0.0002 ± 1.00 Brief cognition Westover USA 2020 50 MMSE 0.11 ± 1.69 Present study India 2024 130 MMSE -0.0009 ± 1.00 HVLT-R: Hopkins verbal learning test- Recall, HVLT-DR: Hopkins verbal learning test- Delayed Recall, IG: Interventional group, CG: Control group, ACE: Addenbrook cognitive examination, TMT-A and B: Trail making test part A and B, COWAT: controlled oral word association test, MMSE: mini-mental state examination Van et al. reported that nearly one-third of BM patients exhibited impaired social cognition, particularly in emotion recognition, potentially impacting both patient and caregiver quality of life (QoL). Emotion recognition is crucial for processing social information and responding appropriately in various social contexts [ 27 ]. Regarding overall QoL, our population reported a mean score of 56.5 ± 32.5, suggesting a perception of a "somewhat bad" quality of life. Functional scale scores in physical, daily living, emotional, social, and cognitive domains were all at or below 60, indicating a general decline in functioning across multiple areas. Conclusion Neurocognitive and (QoL) profiles of BM patients, primarily baseline scores, are useful signposts that guide treatment modalities. In our cohort, while most patients demonstrated normal cognitive function, a significant portion showed cognitive decline, particularly in memory, verbal fluency, and visuospatial abilities. Notably, severe cognitive impairment was found to be associated with factors such as poor performance status (ECOG 2), lower educational level, hypertension, and specific brain lesions, particularly in the left temporal and occipital lobes. Well-preserved cognitive function potentially mandates treatment with focal radiation therapy (SRS) sparing most of the brain parenchyma. On the other hand, poorer cognitive function scores prior to RT may not significantly benefit from focal RT (SRS). Incorporating both neurocognitive assessments and QoL measures into routine clinical practice can serve as a valuable tool in personalized management strategies, ultimately improving patient outcomes by addressing both cognitive health and overall well-being. Declarations Competing interest The authors have no relevant financial or non-financial interests to disclose Ethical approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee of Amrita Institute of Medical Sciences and Research, Kerala, India (IEC-AIMS-2021-PHARM-338). Consent to publish The authors confirm that all human research participants provided informed consent for the publication of data, ensuring their personal identities remain confidential. Funding This study was funded by the Institutional Seed Grant of Amrita Vishwa Vidyapeetham University. Author Contribution HPS and D D- Conception and designHPS and D D- Data collectionHPS and D D- Data analysis and interpretationHPS. D D. NMP. KS.MKU.DC.PA and SM - Manuscript writingHPS. D D. NMP. KS.MKU.DC.PA and SM- Final approval of manuscript Acknowledgement This study is part of a PhD thesis, with the student receiving financial support as a Senior Research Fellow (SRF) from the BAYER Research Foundation in collaboration with BCKIC. We would like to acknowledge the BAYER Research Foundation and BCKIC (Principal Scientific Advisor of the Government of India) for their financial support for the student to conduct this PhD project. Data Availability The data supporting the findings of this study are available from the corresponding author upon reasonable request. References Mitchell DK, Kwon HJ, Kubica PA et al (2022) Brain metastases: An update on the multi-disciplinary approach of clinical management. Neurochirurgie 68:69–85. https://doi.org/10.1016/J.NEUCHI.2021.04.001 Higazy R, Ramotar M, Liu ZA et al (2022) SPCR-04 EFFECTS OF BRAIN METASTASES ON NEUROCOGNITIVE FUNCTION: BASELINE RESULTS OF A LONGITUDINAL TRIAL. Neurooncol Adv 4:i20–i20. https://doi.org/10.1093/NOAJNL/VDAC078.079 Lehrer EJ, Jones BM, Dickstein DR et al (2022) The Cognitive Effects of Radiotherapy for Brain Metastases. Front Oncol 12. https://doi.org/10.3389/FONC.2022.893264 Parsons MW, Peters KB, Floyd SR et al (2021) Preservation of neurocognitive function in the treatment of brain metastases. Neurooncol Adv 3:v96–v107. https://doi.org/10.1093/NOAJNL/VDAB122 Lange M, Joly F, Vardy J et al (2019) Cancer-related cognitive impairment: An update on state of the art, detection, and management strategies in cancer survivors. Ann Oncol 30:1925–1940 Ariello K, Tan H, Soliman H (2021) Narrative review of neurocognitive and quality of life tools used in brain metastases trials. Ann Palliat Med 10:92335–92935. https://doi.org/10.21037/APM-20-1036 Clarke R, Hannan A, Chow H et al (2024) An exploration of intensive care unit patents’ experiences of the Addenbrooke’s Cognitive Examination (ACE-III) as a screening tool for cognitive functioning at different points in recovery from critical illness. https://doi.org/101177/17511437241241242 . https://doi.org/10.1177/17511437241241242 Mathuranath PS, Hodges JR, Mathew R et al (2004) Adaptation of the ACE for a Malayalam speaking population in southern India. Int J Geriatr Psychiatry 19:1188–1194. https://doi.org/10.1002/GPS.1239 EORTC QLQ-C30 | EORTC – Quality of Life https://qol.eortc.org/questionnaires/core/eortc-qlq-c30/ . Accessed 9 Nov 2024 Brain Cancer (update of QLQ-BN20) | EORTC – Quality of Life. https://qol.eortc.org/questionnaire/bn20-update/ . Accessed 9 Nov 2024 Chang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037–1044. https://doi.org/10.1016/S1470-2045(09)70263-3 Van Grinsven EE, Nagtegaal SHJ, Verhoeff JJC, Van Zandvoort MJE (2021) The Impact of Stereotactic or Whole Brain Radiotherapy on Neurocognitive Functioning in Adult Patients with Brain Metastases: A Systematic Review and Meta-Analysis. Oncol Res Treat 44:622–636. https://doi.org/10.1159/000518848 van Grinsven EE, Cialdella F, Verhoeff JJC et al (2023) Different profiles of neurocognitive functioning in patients with brain metastases prior to brain radiotherapy. Psychooncology 32:1752–1761. https://doi.org/10.1002/PON.6229 Handing EP, Leng XI, Kritchevsky SB, Craft S (2020) Association Between Physical Performance and Cognitive Function in Older Adults Across Multiple Studies: A Pooled Analysis Study. Innov Aging 4:1–8. https://doi.org/10.1093/GERONI/IGAA050 Dixon A, Porter S, Suhrie K et al (2022) Predicting daily functioning with the modified Telephone Interview for Cognitive Status. Aging Clin Exp Res 34:1267–1274. https://doi.org/10.1007/S40520-022-02081-4 Krayn-Deckel N, Presaizen K, Kalron A (2024) Cognitive status is associated with performance of manual wheelchair skills in hospitalized older adults. Disabil Rehabil Assist Technol 19:24–29. https://doi.org/10.1080/17483107.2022.2060353 Aminoff EM, Kveraga K, Bar M (2013) The role of the parahippocampal cortex in cognition. Trends Cogn Sci 17:379–390. https://doi.org/10.1016/J.TICS.2013.06.009 Teplyshova AM, Shalimanova EV (2023) Cognitive impairment in temporal lobe epilepsy. Epilepsy paroxysmal conditions 14:355–361. https://doi.org/10.17749/2077-8333/EPI.PAR.CON.2022.134 Schmidbauer V, Nenning KH, Schwarz M et al (2022) Imaging visuospatial memory in temporal lobe epilepsy-Results of an fMRI study. PLoS ONE 17. https://doi.org/10.1371/JOURNAL.PONE.0264349 Gunia A, Moraresku S, Janča R et al (2024) The brain dynamics of visuospatial perspective-taking captured by intracranial EEG. NeuroImage 285:120487. https://doi.org/10.1016/J.NEUROIMAGE.2023.120487 Xie C, Zhong D, Zhang Y et al (2023) Prevalence and risk factors of cognitive impairment in Chinese patients with hypertension: a systematic review and meta-analysis. Front Neurol 14:1271437. https://doi.org/10.3389/FNEUR.2023.1271437/BIBTEX Suvvari TK (2024) Exploring the association between hypertension and cognitive impairment: Evidence-based insights. Chronic Dis Transl Med 10:153–155. https://doi.org/10.1002/CDT3.95 Baggeroer CE, Cambronero FE, Savan NA et al (2024) Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension. Hypertension 81:34–44. https://doi.org/10.1161/HYPERTENSIONAHA.123.19939 Westover KD, Travis Mendel J, Dan T et al (2020) Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer. Neuro Oncol 22:1831–1839. https://doi.org/10.1093/NEUONC/NOAA092 Brown PD, Gondi V, Pugh S et al (2020) Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: Phase III trial NRG oncology CC001. J Clin Oncol 38:1019–1029. https://doi.org/10.1200/JCO.19.02767/SUPPL_FILE/PROTOCOL_JCO.19.02767.PDF Brown PD, Jaeckle K, Ballman KV et al (2016) Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA 316:401–409. https://doi.org/10.1001/JAMA.2016.9839 van Grinsven EE, Cialdella F, Verhoeff JJC et al (2023) Different profiles of neurocognitive functioning in patients with brain metastases prior to brain radiotherapy. Psychooncology 32:1752–1761. https://doi.org/10.1002/PON.6229 Additional Declarations No competing interests reported. Supplementary Files SupplementaryTables31.12.24.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5741939","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":397859503,"identity":"0aa276bf-71a0-4431-8f16-ef1b96890be1","order_by":0,"name":"Haripriya Parapparambil Surendran","email":"","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":false,"prefix":"","firstName":"Haripriya","middleName":"Parapparambil","lastName":"Surendran","suffix":""},{"id":397859505,"identity":"dd1ab734-a98a-455c-bf9b-2c6ca61c4cab","order_by":1,"name":"Debnarayan Dutta","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA40lEQVRIiWNgGAWjYDCCAyCCjSGBTf4xiCkhQ4QWZsYGkBZ+hrQEkBYe4rVINuQYgPiEtfDdyD/+4EeZTZ7BgTOfX92oseBhYD98dAM+LZI3khkbe86lFRsc7N1mnXMM6DCetLQb+LQYALU08LYdTtxwmHebcQ4bUIsEjxlBLY1/2/4nbjjG88w45x+RWpp52w4kzuzhYX6c20aEFskzjw1ny5xLLuaXYDNjzu2T4GEj5Be+44kPPr4ps8tjk2B+/DnnW50cP/vhY3i1IAM2CTBJrHIQYP5AiupRMApGwSgYOQAALclM3FGu1XkAAAAASUVORK5CYII=","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":true,"prefix":"","firstName":"Debnarayan","middleName":"","lastName":"Dutta","suffix":""},{"id":397859507,"identity":"c51224c8-0e3c-495d-975e-c05b6451005a","order_by":2,"name":"Mazhuvancherry Kesavan Unnikrishnan","email":"","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":false,"prefix":"","firstName":"Mazhuvancherry","middleName":"Kesavan","lastName":"Unnikrishnan","suffix":""},{"id":397859508,"identity":"83f8a583-06ad-4d78-94e9-4371cb7e7e73","order_by":3,"name":"Narmadha Mukunthu Poornchary","email":"","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":false,"prefix":"","firstName":"Narmadha","middleName":"Mukunthu","lastName":"Poornchary","suffix":""},{"id":397859509,"identity":"73df01a4-3f50-4295-babc-141d0d79c6de","order_by":4,"name":"Dhanya Chandran","email":"","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":false,"prefix":"","firstName":"Dhanya","middleName":"","lastName":"Chandran","suffix":""},{"id":397859510,"identity":"2e02d33c-2849-4acd-89bc-034dcd742030","order_by":5,"name":"Sruthi Kalavagunta","email":"","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":false,"prefix":"","firstName":"Sruthi","middleName":"","lastName":"Kalavagunta","suffix":""},{"id":397859511,"identity":"4751f1e3-02c6-4780-afd8-231353c7ec05","order_by":6,"name":"Parasuraman Ayiramuthu","email":"","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":false,"prefix":"","firstName":"Parasuraman","middleName":"","lastName":"Ayiramuthu","suffix":""},{"id":397859512,"identity":"4a587b5e-3113-4b58-a596-89164b4aabab","order_by":7,"name":"Sabitha Mangalath","email":"","orcid":"","institution":"Amrita Vishwa Vidyapeetham University","correspondingAuthor":false,"prefix":"","firstName":"Sabitha","middleName":"","lastName":"Mangalath","suffix":""}],"badges":[],"createdAt":"2024-12-31 12:23:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5741939/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5741939/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":73049493,"identity":"475928b5-a843-449b-b815-279cd0c14e00","added_by":"auto","created_at":"2025-01-06 09:17:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63745,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5741939/v1/76e0de43113708fac842bf51.png"},{"id":73049497,"identity":"92c9a62c-ab72-4384-aa61-c3d161441414","added_by":"auto","created_at":"2025-01-06 09:17:50","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":47619,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of neurocognitive score (ACE score) among patients\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5741939/v1/5b2e79271de8658614f99474.png"},{"id":74497640,"identity":"cfb9ecc2-0205-443e-8c97-7cddaeae898e","added_by":"auto","created_at":"2025-01-22 23:46:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1184922,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5741939/v1/58c46262-df89-441b-9864-77b27ee25f64.pdf"},{"id":73051428,"identity":"b9d42fbe-20e6-43cb-83f9-38ce3b54747a","added_by":"auto","created_at":"2025-01-06 09:25:50","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18716,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTables31.12.24.docx","url":"https://assets-eu.researchsquare.com/files/rs-5741939/v1/d4f9d240abbcd2393ddd2681.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neurocognitive and QoL Profiles as a Tools for Informed Decisions in Brain Metastasis Management: Analysis from A Prospective Randomized Placebo-Controlled Trial (CTRI/2022/01/039599).","fulltext":[{"header":"Importance of the study","content":"\u003cp\u003eThis study provides critical insights into the neurocognitive and quality-of-life (QoL) profiles of brain metastases (BM) patients, highlighting the significance of baseline evaluations. Prior literature has identified cognitive decline and poor QoL as prevalent issues in BM patients, but this study uniquely correlates specific predictors\u0026mdash;such as performance status, education, hypertension, and lesion location\u0026mdash;with neurocognitive outcomes. The findings emphasize the utility of neurocognitive assessments and QoL tools in personalizing treatment strategies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eValidated, brief screening tools such as the Addenbrooke\u0026apos;s Cognitive Examination and EORTC QoL questionnaires, helped us to prioritise interventional methods to improve patient care. \u0026nbsp;Tailored interventions addressing cognitive and QoL challenges could optimize treatment decisions and long-term outcomes. Future implications include integrating these assessments into standard care protocols to support informed decision-making, enhance therapeutic efficacy, and improve BM patient care.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eAdvancements in the management of brain metastases (BM) have significantly improved outcomes and increased survival rates, prompting research focus on cognitive impairments and quality of life (QoL) related to both disease and therapy[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Literature on cognitive decline after radiation therapy is heterogeneous, with memory, attention, processing speed, and executive functioning identified as the most frequently impaired cognitive domains in BM[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. BM patients experience cognitive impairments on account of BM itself, medication use, the primary cancer, and side effects of radiotherapy and chemotherapy[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Thorough assessment and understanding of cognitive impairments are critical because they can negatively affect informed medical decisions, choice of radiation modalities, preserving daily functioning, and QoL. Neurocognitive assessment (NCA) before treatment is also crucial for evaluating neurocognitive changes following radiation or further management of BM[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite NCA being an objective test for neurocognitive profiling of newly diagnosed BM patients, morbidity and the long duration (2 to 3 hrs) limit wider coverage. The Addenbrooke's Cognitive Examination (ACE) is brief, yet sensitive cognitive screening tool[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. ACE is comprehensive, brief (15 to 20 minutes) and evaluates attention, orientation, memory (recall, anterograde memory, retrograde memory, and delayed recall), language, and visuospatial abilities [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLikewise, there is a paucity of data on the QoL in BM patients, which directly correlates with overall well-being and functional status. We assessed QoL using a combination of (a) the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), and (b) the EORTC Quality of Life Questionnaire-Brain Neoplasm 20 (EORTC QLQ-BN20) in BM patients before commencing radiation therapy[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis report is part of a prospective placebo-controlled randomized trial investigating the role of memantine in preserving neurocognitive functions during radiotherapy in BM (CTRI/2022/01/039599) and was approved by the Institutional Ethics Committee (IEC-AIMS-2021-PHARM-338). The key inclusion criteria were: either gender, 18 years and older; diagnosis of solid malignancy with BM visible on contrast-enhanced MRI (or CT for patients unable to have an MRI); sufficient fluency in English, Malayalam, or Hindi and willingness to complete the cognitive function test and the QoL questionnaires with an ECOG performance status of 0, 1, or 2. The exclusion criteria included: patients not willing to participate; psychiatric illness, drug abuse, or mental retardation (premorbid intelligence quotient\u0026thinsp;\u0026lt;\u0026thinsp;70); history of prior cranial external beam radiotherapy; and currently using NMDA antagonists such as amantadine, ketamine, or dextromethorphan. Patients were screened by the radiation oncologist and a clinical pharmacologist during the first consultation. Baseline data were collected from the trial data.\u003c/p\u003e \u003cp\u003eA neuropsychologist performed NCA (before treatment) using ACE which evaluates cognitive domains such as attention and orientation, memory (encompassing recall, anterograde memory, retrograde memory, and delayed recall), language, and visuospatial abilities, yielding a score from 0 to 100, with domain-specific allocations (attention and orientation (18 points), memory (35 points), fluency (14 points), language (28 points), and visuospatial skills (5 points). (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNeurocognitive functions and assessments used for analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive domains\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCognitive functions\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTest used\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBasic cognition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAttention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRepeating words, subtractions, or backward spelling\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOrientation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime, place\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVerbal function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVerbal fluency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLetter and category naming test\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLanguage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNaming test, comprehension (1-stage, reading, 3-stage, complex grammar), repetition (single words and phrases), reading (regular and irregular), and writing\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisuospatial function\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVisuospatial abilities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOverlapping pentagons,\u003c/p\u003e \u003cp\u003eWire cube, clock drawing\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemory\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMemory, recall, ante retrograde memory, retrograde memory, delayed recall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRecall test, address test, delayed recall test, and retrograde memory test.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe assessed QoL using EORTC QLQ-C30, version 3, and BN20. The QLQ-C30 is a core measure designed for all patients and includes five functional scales\u0026mdash;physical, role (daily life), emotional, cognitive, and social; three symptom scales\u0026mdash;fatigue, nausea and vomiting, and pain; and six single-item scales\u0026mdash;dyspnoea, insomnia, appetite loss, constipation, diarrhoea, the financial impact of the tumour and treatment, and overall quality of life. The QLQ-BN20 consists of 20 items that assess visual disorders, motor dysfunction, communication deficits, various disease symptoms (e.g., headaches and seizures), treatment-related toxic effects (e.g., hair loss), and future uncertainty. Items from both questionnaires were scaled and scored using the recommended EORTC procedures. Raw scores were transformed to a linear scale ranging from 0 to 100.\u003c/p\u003e \u003cp\u003eHigher QLQ-C30, scores in functional domains indicate better functioning, while higher scores in symptom domains indicate more symptoms. On the other hand, lower QLQ-BN20, scores indicate fewer symptoms and better QoL. The patients themselves filled QoL questionnaires, (with help from caregivers if required) during their first few visits (before radiation therapy).\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eWe conducted all statistical analyses using IBM SPSS Statistics version 26.0. Descriptive statistics were employed to assess the patient cohort's baseline demographic, clinical, treatment, cognitive, and QoL parameters. The neurocognitive status of patients was categorized based on the mean ACE score of 75.19. We classified patients with a score of 75.19 or above as having normal cognitive performance. Cognitive decline was further categorized as follows:\u003c/p\u003e \u003cp\u003eMild Cognitive Decline: A decline of 1 SD (18.67) from the mean ACE score of 75.19.\u003c/p\u003e \u003cp\u003eModerate Cognitive Decline: A decline of 2 SDs (37.34) from the mean ACE score.\u003c/p\u003e \u003cp\u003eSevere Cognitive Impairment: Scores falling below the 2 SD decline threshold.\u003c/p\u003e \u003cp\u003eIn addition to mean ACE scores, we computed Z-scores for the ACE and its specific domains. The Z-score was calculated using the formula \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:x-\\stackrel{-}{x}∕SD\\)\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003cp\u003eWhere \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\stackrel{-}{x}\\:\\)\u003c/span\u003e\u003c/span\u003erepresents the mean score from the dataset.\u003c/p\u003e \u003cp\u003eWe performed univariate analysis to explore the relationship between predisposing factors and the four categories of cognitive status. The subsequent multinomial logistic regression analysis was performed for the variables that demonstrated significant differences (p\u0026thinsp;\u0026lt;\u0026thinsp;0.1) in univariate analysis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOne thirty patients prospectively enrolled in the memantine trial (CTRI/2022/01/039599) and proceeded with NCA and QoL assessment (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Participants ranged between the ages of 31 and 75 years of age at the time of assessment. The majority were right-handed (98.4%). Twenty-six patients underwent surgery before assessment. NCA and QoL were administered 2 to 3 weeks after surgery. The patient demographics, tumour, clinical and treatment characteristics are presented in Supplementary Table\u0026nbsp;1. The mean cognitive performance of study participants was found to be 75.19\u0026thinsp;\u0026plusmn;\u0026thinsp;18.67. The neuropsychological profile of patients with BM is summarised in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDomain-wise cognitive performance of enrolled patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive assessments (range)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMinimum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMaximum\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean Score\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eZ score\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eACE\u003c/b\u003e (0-100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e75.19\u0026thinsp;\u0026plusmn;\u0026thinsp;18.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.02\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOrientation (0\u0026ndash;10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.48\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.002\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAttention (0\u0026ndash;8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e6.27\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e-0.002\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMemory (0\u0026ndash;35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e23.27\u0026thinsp;\u0026plusmn;\u0026thinsp;7.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.04\u0026thinsp;\u003cb\u003e\u0026plusmn;\u003c/b\u003e\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRecall (0\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.002\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnte retrograde memory (0\u0026ndash;21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.73\u0026thinsp;\u0026plusmn;\u0026thinsp;4.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.0009\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetrograde memory (0\u0026ndash;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e-0.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDelayed recall (0\u0026ndash;7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.25\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.003\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVerbal Fluency (0\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e9.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.0002\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLanguage (0\u0026ndash;28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e25.03\u0026thinsp;\u0026plusmn;\u0026thinsp;4.62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e0.0003\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVisuospatial abilities (0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e-1.927\u0026thinsp;\u0026plusmn;\u0026thinsp;0.53\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMSE (0\u0026ndash;30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e24.63\u0026thinsp;\u0026plusmn;\u0026thinsp;5.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e \u003cp\u003e-0.0009\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong the study participants, 78 patients (60.0%) exhibited normal cognitive functioning with scores of 75 or higher. A cognitive decline of 1 SD was observed in 37 patients (28.5%), with scores ranging from 74 to 56. A cognitive decline of 2 standard deviations was noted in 8 patients (6.2%), with scores between 55 and 38. Severe cognitive impairment, characterized by scores below 37, was present in 7 patients (5.4%). Details are provided in Supplementary Table\u0026nbsp;2 and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePoor performance status (ECOG 2) correlated with severe cognitive impairment (19%) and vice versa (ECOG 0; 4.2% severe cognitive impairment). Likewise, mild and moderate cognitive impairment and performance status were significantly correlated (p\u0026thinsp;=\u0026thinsp;0.001). Patients below graduation had severe cognitive impairment (7.2%) compared to those above graduation (2.1%; p\u0026thinsp;=\u0026thinsp;0.004). Additionally, hypertensive patients demonstrated greater cognitive impairment than normotensives (11.1% vs. 3.2% p\u0026thinsp;=\u0026thinsp;0.03). Lesions in the left temporal lobe and left occipital lobe were also significantly associated with cognitive impairment (p-values\u0026thinsp;=\u0026thinsp;0.006 and 0.03, respectively). Of those with severe cognitive impairment, 6.7% had undergone prior surgery (p\u0026thinsp;=\u0026thinsp;0.002) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \n\u003cp\u003eTable 3: Univariate Analysis of Factors Associated with Cognitive Impairment\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"671\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eNormal cognition (\u0026gt;=75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eMild cognitive impairment\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(74-56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eModerate cognitive impairment (55-38)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003eSevere cognitive impairment\u003c/p\u003e\n \u003cp\u003e(\u0026lt;37)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eP Value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003cp\u003e\u0026lt;55\u003c/p\u003e\n \u003cp\u003e\u0026gt;56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50 (66.7%)\u003c/p\u003e\n \u003cp\u003e28 (50.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e16 (21.3%)\u003c/p\u003e\n \u003cp\u003e21 (38.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (8%)\u003c/p\u003e\n \u003cp\u003e2 (3.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (4%)\u003c/p\u003e\n \u003cp\u003e4 (7.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40 (83.3%)\u003c/p\u003e\n \u003cp\u003e31 (50.8%)\u003c/p\u003e\n \u003cp\u003e7 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (8.3%)\u003c/p\u003e\n \u003cp\u003e24 (39.3%)\u003c/p\u003e\n \u003cp\u003e9 (42.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (4.2%)\u003c/p\u003e\n \u003cp\u003e5 (8.2%)\u003c/p\u003e\n \u003cp\u003e1 (4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (4.2%)\u003c/p\u003e\n \u003cp\u003e1 (1.6%)\u003c/p\u003e\n \u003cp\u003e4 (19.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eHandedness\u003c/p\u003e\n \u003cp\u003eRight\u003c/p\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e76 (59.4%)\u003c/p\u003e\n \u003cp\u003e2 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e37 (28.9%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (6.3%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (5.5%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eEmployment at the time of analysis\u003c/p\u003e\n \u003cp\u003eWorking\u003c/p\u003e\n \u003cp\u003eNot working\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38 (80.6%)\u003c/p\u003e\n \u003cp\u003e49 (52.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (11.1%)\u003c/p\u003e\n \u003cp\u003e33 (35.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (8.3%)\u003c/p\u003e\n \u003cp\u003e5 (5.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e7 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eEducation\u003c/p\u003e\n \u003cp\u003eAbove graduate\u003c/p\u003e\n \u003cp\u003eBelow graduate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e38 (80.9%)\u003c/p\u003e\n \u003cp\u003e40 (48.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (12.8%)\u003c/p\u003e\n \u003cp\u003e31 (37.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (4.3%)\u003c/p\u003e\n \u003cp\u003e6 (7.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (2.1%)\u003c/p\u003e\n \u003cp\u003e3 (7.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eComorbidity\u003c/p\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (52.4%)\u003c/p\u003e\n \u003cp\u003e45 (67.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (33.3%)\u003c/p\u003e\n \u003cp\u003e16 (23.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (6.3%)\u003c/p\u003e\n \u003cp\u003e4 (6.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e(7.9%)\u003c/p\u003e\n \u003cp\u003e(3.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (41.7%)\u003c/p\u003e\n \u003cp\u003e63 (67.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (41.7%)\u003c/p\u003e\n \u003cp\u003e22 (23.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (5.6%)\u003c/p\u003e\n \u003cp\u003e6 (6.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (11.1%)\u003c/p\u003e\n \u003cp\u003e4 (3.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003ePrimary site\u003c/p\u003e\n \u003cp\u003eLung\u003c/p\u003e\n \u003cp\u003eBreast\u003c/p\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (53.5%)\u003c/p\u003e\n \u003cp\u003e32 (65.3%)\u003c/p\u003e\n \u003cp\u003e23 (60.5%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (32.6%)\u003c/p\u003e\n \u003cp\u003e10 (20.4%)\u003c/p\u003e\n \u003cp\u003e13 (34.2 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (4.7%)\u003c/p\u003e\n \u003cp\u003e5 (10.2%)\u003c/p\u003e\n \u003cp\u003e1 (2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (9.3%)\u003c/p\u003e\n \u003cp\u003e2 (4.1%)\u003c/p\u003e\n \u003cp\u003e1 (2.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eType of primary\u003c/p\u003e\n \u003cp\u003eCommon primary\u003c/p\u003e\n \u003cp\u003eRare primary\u003c/p\u003e\n \u003cp\u003eUncommon primary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;67 (59.8%)\u003c/p\u003e\n \u003cp\u003e1 (100%)\u003c/p\u003e\n \u003cp\u003e10 (58.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (28.6%)\u003c/p\u003e\n \u003cp\u003e10 (0.0%)\u003c/p\u003e\n \u003cp\u003e13 (29.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (6.3%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e1 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (5.4%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e1 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eMetastases sites\u003c/p\u003e\n \u003cp\u003eBrain only\u003c/p\u003e\n \u003cp\u003eBrain and other extracranial sites\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47 (58%)\u003c/p\u003e\n \u003cp\u003e31 (63.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e25 (30.9%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;12 (24.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.7%)\u003c/p\u003e\n \u003cp\u003e5 (10.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (7.4%)\u003c/p\u003e\n \u003cp\u003e1 (2.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003ePresentation of metastases\u003c/p\u003e\n \u003cp\u003eMetachronous\u003c/p\u003e\n \u003cp\u003eSynchronous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e53 (61.6%)\u003c/p\u003e\n \u003cp\u003e25 (56.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e20 (23.3%)\u003c/p\u003e\n \u003cp\u003e17 (38.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (9.3%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (5.8%)\u003c/p\u003e\n \u003cp\u003e2 (4.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eTumour location\u003c/p\u003e\n \u003cp\u003eRight\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eLeft\u003c/p\u003e\n \u003cp\u003eMedial\u003c/p\u003e\n \u003cp\u003eBilateral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (63.6%)\u003c/p\u003e\n \u003cp\u003e21 (58.3%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;3 (60.0%)\u003c/p\u003e\n \u003cp\u003e40 (59.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (36.4%)\u003c/p\u003e\n \u003cp\u003e11 (30.6%)\u003c/p\u003e\n \u003cp\u003e1 (20.0%)\u003c/p\u003e\n \u003cp\u003e17 (25.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e2 (5.6%)\u003c/p\u003e\n \u003cp\u003e1 (20.4%)\u003c/p\u003e\n \u003cp\u003e5 (25.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e2 (5.6%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e5 (7.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eNumber of lesions\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003cp\u003eMultiple\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (57.9%)\u003c/p\u003e\n \u003cp\u003e17 (68.0%)\u003c/p\u003e\n \u003cp\u003e39 (59.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e13 (34.2%)\u003c/p\u003e\n \u003cp\u003e7 (28.0%)\u003c/p\u003e\n \u003cp\u003e17 (25.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (7.9%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e4 (6.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e1 (4.0%)\u003c/p\u003e\n \u003cp\u003e6 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eRPA Class\u003c/p\u003e\n \u003cp\u003eClass 1\u003c/p\u003e\n \u003cp\u003eClass 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47 (75.8%)\u003c/p\u003e\n \u003cp\u003e31 (45.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e12 (19.4%)\u003c/p\u003e\n \u003cp\u003e25 (36.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1 (1.6%)\u003c/p\u003e\n \u003cp\u003e7 (10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (3.2%)\u003c/p\u003e\n \u003cp\u003e5 (7.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"top\" style=\"width: 671px;\"\u003e\n \u003cp\u003eLocation of lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eBrain stem\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;67 (60.9%)\u003c/p\u003e\n \u003cp\u003e11 (55.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32 (29.1%)\u003c/p\u003e\n \u003cp\u003e5 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (5.5%)\u003c/p\u003e\n \u003cp\u003e2 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (4.5%)\u003c/p\u003e\n \u003cp\u003e2 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eRight frontal\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e47 (61.0%)\u003c/p\u003e\n \u003cp\u003e31 (59.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (29.9%)\u003c/p\u003e\n \u003cp\u003e13 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.9%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;5 (9.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (5.2%)\u003c/p\u003e\n \u003cp\u003e3 (5.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eLeft frontal\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e50 (60.2%)\u003c/p\u003e\n \u003cp\u003e27 (58.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (28.9%)\u003c/p\u003e\n \u003cp\u003e13 (28.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (7.2%)\u003c/p\u003e\n \u003cp\u003e2 (4.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.6%)\u003c/p\u003e\n \u003cp\u003e4 (8.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eMedial temporal\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e69 (61.6%)\u003c/p\u003e\n \u003cp\u003e9 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31 (27.7%)\u003c/p\u003e\n \u003cp\u003e6 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (6.3%)\u003c/p\u003e\n \u003cp\u003e1 (5.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (4.5%)\u003c/p\u003e\n \u003cp\u003e2 (11.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eNear to hippocampus\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e70 (61.4%)\u003c/p\u003e\n \u003cp\u003e8 (50.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e35 (28.1%)\u003c/p\u003e\n \u003cp\u003e5 (31.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (6.1%)\u003c/p\u003e\n \u003cp\u003e1 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (4.4%)\u003c/p\u003e\n \u003cp\u003e2 (12.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eRight temporal\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e65 (59.1%)\u003c/p\u003e\n \u003cp\u003e13 (65.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e33 (30.0%)\u003c/p\u003e\n \u003cp\u003e4 (20.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (6.4%)\u003c/p\u003e\n \u003cp\u003e1 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (4.5%)\u003c/p\u003e\n \u003cp\u003e2 (10.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eLeft temporal\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e62 (61.4%)\u003c/p\u003e\n \u003cp\u003e16 (55.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32 (31.7%)\u003c/p\u003e\n \u003cp\u003e5 (17.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (5.0%)\u003c/p\u003e\n \u003cp\u003e3 (10.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (2.0%)\u003c/p\u003e\n \u003cp\u003e5 (17.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eRight parietal\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58 (62.4%)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;20 (54.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (28.0%)\u003c/p\u003e\n \u003cp\u003e11 (29.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (6.5%)\u003c/p\u003e\n \u003cp\u003e2 (5.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.2%)\u003c/p\u003e\n \u003cp\u003e4 (10.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eLeft parietal\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e49 (59.8%)\u003c/p\u003e\n \u003cp\u003e29 (60.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (26.8%)\u003c/p\u003e\n \u003cp\u003e15 (31.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e7 (8.5%)\u003c/p\u003e\n \u003cp\u003e1 (2.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (4.9%)\u003c/p\u003e\n \u003cp\u003e3 (6.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eRight occipital\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e58 (59.4%)\u003c/p\u003e\n \u003cp\u003e20 (60.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e32 (31.7%)\u003c/p\u003e\n \u003cp\u003e5 (17.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (5.9%)\u003c/p\u003e\n \u003cp\u003e2 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.0%)\u003c/p\u003e\n \u003cp\u003e4 (14.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eLeft occipital\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e61 (62.2%)\u003c/p\u003e\n \u003cp\u003e16 (51.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e30 (30.6%)\u003c/p\u003e\n \u003cp\u003e7 (22.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.1%)\u003c/p\u003e\n \u003cp\u003e5 (16.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (4.1%)\u003c/p\u003e\n \u003cp\u003e3 (9.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eRight cerebellum\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51 (57.3%)\u003c/p\u003e\n \u003cp\u003e26 (65.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e27 (30.3%)\u003c/p\u003e\n \u003cp\u003e10 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e6 (6.7%)\u003c/p\u003e\n \u003cp\u003e2 (5.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e5 (5.6%)\u003c/p\u003e\n \u003cp\u003e2 (5.05%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eLeft cerebellum\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e43 (56.6%)\u003c/p\u003e\n \u003cp\u003e34 (64.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (34.2%)\u003c/p\u003e\n \u003cp\u003e11 (20.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (3.9%)\u003c/p\u003e\n \u003cp\u003e5 (9.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4 (5.3%)\u003c/p\u003e\n \u003cp\u003e3 (5.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003ePrior surgery\u003c/p\u003e\n \u003cp\u003eNot done\u003c/p\u003e\n \u003cp\u003eDone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e67 (64.4%)\u003c/p\u003e\n \u003cp\u003e11 (42.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e22 (21.2%)\u003c/p\u003e\n \u003cp\u003e15 (57.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (7.7%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e8 (6.7%)\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003ePrior chemotherapy\u003c/p\u003e\n \u003cp\u003eNot done\u003c/p\u003e\n \u003cp\u003eDone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e26 (57.8%)\u003c/p\u003e\n \u003cp\u003e52 (61.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (37.8%)\u003c/p\u003e\n \u003cp\u003e20 (23.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003cp\u003e8 (9.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (4.4%)\u003c/p\u003e\n \u003cp\u003e5 (5.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eSteroid at the time of analysis\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36 (60.0%)\u003c/p\u003e\n \u003cp\u003e42 (60.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e19 (31.7%)\u003c/p\u003e\n \u003cp\u003e18 (25.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3 (5.0%)\u003c/p\u003e\n \u003cp\u003e5 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 104px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (3.3%)\u003c/p\u003e\n \u003cp\u003e5 (7.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cp\u003eWe conducted multinomial logistic regression on variables with a p\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in the univariate analysis (ECOG, employment, education, hypertension, metastases, RPA class, left temporal lobe lesions and bilateral occipital lobes, prior surgery/ chemotherapy). Risk for severe cognitive impairment was significantly lower in patients with above-graduate education (OR\u0026thinsp;=\u0026thinsp;0.002, 95% CI: 0.57 to 0.73; p\u0026thinsp;=\u0026thinsp;0.03). Hypertension and lesions in the left temporal lobe significantly increased risk of cognitive impairment, with OR\u0026thinsp;=\u0026thinsp;52.08 (95% CI: 1.88 to 1441.3), p\u0026thinsp;=\u0026thinsp;0.02, and OR\u0026thinsp;=\u0026thinsp;71.40 (95% CI: 1.16 to 4393.2), p\u0026thinsp;=\u0026thinsp;0.04, respectively. (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \n\u003cp\u003eTable 4: Multinomial logistic regression analysis to determine the relationship between functional outcomes and demographic and clinical predictors.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eCognitive dysfunctional status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003ePredisposing factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003eLower bound-upper bound\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eMild cognitive impairment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003eEmployment\u003c/p\u003e\n \u003cp\u003eWorking\u003c/p\u003e\n \u003cp\u003eNot working\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.04 to 1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003eECOG\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003cp\u003e0.62\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003col start=\"0\"\u003e\n \u003cli\u003eto 0.36\u003c/li\u003e\n \u003c/ol\u003e\n \u003cp\u003e0.14 to 2.60\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003cp\u003e0.51\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003ePrior surgery\u003c/p\u003e\n \u003cp\u003eDone\u003c/p\u003e\n \u003cp\u003eNot done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.02 to 0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" valign=\"top\" style=\"width: 135px;\"\u003e\n \u003cp\u003eSevere cognitive impairment\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003eEducation\u003c/p\u003e\n \u003cp\u003eAbove graduate\u003c/p\u003e\n \u003cp\u003eBelow graduate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.57 to 0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e52.08\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.88 to 1441.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 139px;\"\u003e\n \u003cp\u003eLeft temporal\u003c/p\u003e\n \u003cp\u003ePresent\u003c/p\u003e\n \u003cp\u003eAbsent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 123px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e71.40\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.16 to 4393.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\u003cp\u003e130 patients filled out the baseline QoL questionnaire (only 115 patients (88.4%) completed the questionnaire independently, 15 patients (11.5%) required assistance) (see supplementary Table\u0026nbsp;3)\u003c/p\u003e \u003cp\u003eGlobal QoL score (56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;32.5) indicated a \u0026ldquo;somewhat bad quality of life\u0026rdquo;. All functional scales (physical, daily life, emotional, social, and cognitive) scores were below 60. Except for gastrointestinal symptoms, all symptom scores were elevated in BM. The BN-20 domain scores were not significantly elevated in our population.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis prospective study offers important insights into the neurocognitive functioning of BM patients before radiation therapy. Most participants demonstrated normal cognitive performance, (ACE score\u0026thinsp;\u0026gt;\u0026thinsp;75) before treatment. However, the cognitive deficit was significant in 28% and 6.2% of patients with 1 and 2 SD decline respectively. A smaller group (5.4%) had severe cognitive impairment (ACE scores\u0026thinsp;\u0026lt;\u0026thinsp;37) Memory, (particularly ante retrograde memory, delayed recall), verbal fluency, and visuospatial abilities, were the most affected. There was significant variability in cognitive functioning within the cohort, necessitating comprehensive neurocognitive assessment before initiating treatment.\u003c/p\u003e \u003cp\u003eThe above results align with previous studies that report 53\u0026ndash;67% exhibiting cognitive impairments on at least one cognitive test before radiotherapy[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, 60% of patients in our study demonstrated normal cognitive functioning prior to treatment possibly on account of higher level of education (all above elementary school) and a reasonable performance status score below ECOG 2. In contrast, other reports show cognitive impairments in up to 79% BM patients prior to treatment. Differences in performance status and educational level may influence baseline cognitive dysfunction [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePoor performance status correlated with significant cognitive impairment (ECOG 2 in 19% vs ECOG 0 in 4.2% p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). This aligns with previous findings showing a strong correlation between cognitive function and performance status. For instance, Handing et al. (2020) reported that better cognitive scores, particularly on the Digit Symbol Substitution Task, were associated with improved physical function[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Similarly, cognitive screening tools like the modified Telephone Interview for Cognitive Status (mTICS) have been shown to predict daily functioning in older adults with mild cognitive impairment (Dixon et al., 2022)[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Additionally, Krayn-Deckel et al. (2022) found that cognitive impairment negatively impacted manual skills in hospitalized individuals, reinforcing the importance of physical and daily functioning as a predictor of cognitive function [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLeft temporal lobe is critical for memory functions, with lesions signifying cognitive impairment, which align with our results. [OR\u0026thinsp;=\u0026thinsp;71.4 (1.16 to 4393.2), p\u0026thinsp;=\u0026thinsp;0.04]. Specifically, lesions in the hippocampus and parahippocampal gyrus in the left temporal lobe cause significant memory impairments (Schmidbauer et al., 2022; Teplyshova \u0026amp; Shalimanova, 2023)[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Additionally, activation of the left mesiotemporal structures has been positively correlated with better memory encoding and retrieval (Schmidbauer et al., 2022)[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eLesions in the left occipital lobe, integral to visuospatial processing, were also significantly associated with cognitive impairment (p\u0026thinsp;=\u0026thinsp;0.03). Damage to this region can impair spatial awareness and visual memory, further supporting the importance of these brain regions in overall cognitive function[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHypertensive patients showed greater cognitive decline (11.1% vs. 3.2%, p\u0026thinsp;=\u0026thinsp;0.03) than normotensives, which aligns with previous reports. A systematic review found that approximately 37.6% of patients with hypertension experience cognitive impairment (Xie et al., 2024)[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Prevalence of cognitive impairment among hypertensive patients have reached up to 43.6% (Suvvari, 2023)[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ez-scores (index of overall neurocognition) of our cohorts were different from similar reports involving other populations. Recall, delayed recall and verbal fluency scores were lower than our scores in reports from previous studies. However, attention scores were similar across diverse populations, including our own[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR24 CR25\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. (See Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eNeurocognitive Profiles in Brain Metastases Patients Across Different studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCognitive domain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFirst Author\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSample size\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTest used\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eZ score\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eRecall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChang EL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003cp\u003eCG: -0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWestover\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-R\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003cp\u003eCG: -1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eACE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.002\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eDelayed recall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChang EL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-DR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003cp\u003eCG: -0.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e111\u0026thinsp;+\u0026thinsp;102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-DR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003c/p\u003e \u003cp\u003eCG: -1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e98\u0026thinsp;+\u0026thinsp;96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-DR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003cp\u003eCG: -1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWestover\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-DR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHVLT-DR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: 1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003cp\u003eCG: 1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eACE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.003\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"8\" rowspan=\"9\"\u003e \u003cp\u003eAttention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eChang EL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -2.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003cp\u003eCG: -1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003cp\u003eCG: -2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e111\u0026thinsp;+\u0026thinsp;102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003cp\u003eCG: -1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003cp\u003eCG: -3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e98\u0026thinsp;+\u0026thinsp;96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0\u003c/p\u003e \u003cp\u003eCG: -1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4\u003c/p\u003e \u003cp\u003eCG: -2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eWestover\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTMT-B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eACE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.002\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eVerbal fluency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eChang EL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMAE-COWA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -0.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003cp\u003eCG: -0.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e111\u0026thinsp;+\u0026thinsp;102\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCOWAT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -1.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003cp\u003eCG: -1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWestover\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCOWAT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.86\u0026thinsp;\u0026plusmn;\u0026thinsp;1.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBrown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e518\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCOWAT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIG: -0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003cp\u003eCG: -0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eACE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0002\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBrief cognition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWestover\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMMSE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.11\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePresent study\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2024\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMMSE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.0009\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eHVLT-R: Hopkins verbal learning test- Recall, HVLT-DR: Hopkins verbal learning test- Delayed Recall, IG: Interventional group, CG: Control group, ACE: Addenbrook cognitive examination, TMT-A and B: Trail making test part A and B, COWAT: controlled oral word association test, MMSE: mini-mental state examination\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVan et al. reported that nearly one-third of BM patients exhibited impaired social cognition, particularly in emotion recognition, potentially impacting both patient and caregiver quality of life (QoL). Emotion recognition is crucial for processing social information and responding appropriately in various social contexts [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Regarding overall QoL, our population reported a mean score of 56.5\u0026thinsp;\u0026plusmn;\u0026thinsp;32.5, suggesting a perception of a \"somewhat bad\" quality of life. Functional scale scores in physical, daily living, emotional, social, and cognitive domains were all at or below 60, indicating a general decline in functioning across multiple areas.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eNeurocognitive and (QoL) profiles of BM patients, primarily baseline scores, are useful signposts that guide treatment modalities. In our cohort, while most patients demonstrated normal cognitive function, a significant portion showed cognitive decline, particularly in memory, verbal fluency, and visuospatial abilities. Notably, severe cognitive impairment was found to be associated with factors such as poor performance status (ECOG 2), lower educational level, hypertension, and specific brain lesions, particularly in the left temporal and occipital lobes.\u003c/p\u003e \u003cp\u003eWell-preserved cognitive function potentially mandates treatment with focal radiation therapy (SRS) sparing most of the brain parenchyma. On the other hand, poorer cognitive function scores prior to RT may not significantly benefit from focal RT (SRS). Incorporating both neurocognitive assessments and QoL measures into routine clinical practice can serve as a valuable tool in personalized management strategies, ultimately improving patient outcomes by addressing both cognitive health and overall well-being.\u003c/p\u003e"},{"header":"Declarations","content":" \u003ch2\u003eCompeting interest\u003c/h2\u003e \u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eEthical approval\u003c/h2\u003e \u003cp\u003e This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethics Committee of Amrita Institute of Medical Sciences and Research, Kerala, India (IEC-AIMS-2021-PHARM-338).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to publish\u003c/strong\u003e \u003cp\u003eThe authors confirm that all human research participants provided informed consent for the publication of data, ensuring their personal identities remain confidential.\u003c/p\u003e \u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was funded by the Institutional Seed Grant of Amrita Vishwa Vidyapeetham University.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eHPS and D D- Conception and designHPS and D D- Data collectionHPS and D D- Data analysis and interpretationHPS. D D. NMP. KS.MKU.DC.PA and SM - Manuscript writingHPS. D D. NMP. KS.MKU.DC.PA and SM- Final approval of manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThis study is part of a PhD thesis, with the student receiving financial support as a Senior Research Fellow (SRF) from the BAYER Research Foundation in collaboration with BCKIC. We would like to acknowledge the BAYER Research Foundation and BCKIC (Principal Scientific Advisor of the Government of India) for their financial support for the student to conduct this PhD project.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMitchell DK, Kwon HJ, Kubica PA et al (2022) Brain metastases: An update on the multi-disciplinary approach of clinical management. Neurochirurgie 68:69\u0026ndash;85. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/J.NEUCHI.2021.04.001\u003c/span\u003e\u003cspan address=\"10.1016/J.NEUCHI.2021.04.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHigazy R, Ramotar M, Liu ZA et al (2022) SPCR-04 EFFECTS OF BRAIN METASTASES ON NEUROCOGNITIVE FUNCTION: BASELINE RESULTS OF A LONGITUDINAL TRIAL. Neurooncol Adv 4:i20\u0026ndash;i20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/NOAJNL/VDAC078.079\u003c/span\u003e\u003cspan address=\"10.1093/NOAJNL/VDAC078.079\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLehrer EJ, Jones BM, Dickstein DR et al (2022) The Cognitive Effects of Radiotherapy for Brain Metastases. Front Oncol 12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/FONC.2022.893264\u003c/span\u003e\u003cspan address=\"10.3389/FONC.2022.893264\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eParsons MW, Peters KB, Floyd SR et al (2021) Preservation of neurocognitive function in the treatment of brain metastases. Neurooncol Adv 3:v96\u0026ndash;v107. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/NOAJNL/VDAB122\u003c/span\u003e\u003cspan address=\"10.1093/NOAJNL/VDAB122\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLange M, Joly F, Vardy J et al (2019) Cancer-related cognitive impairment: An update on state of the art, detection, and management strategies in cancer survivors. Ann Oncol 30:1925\u0026ndash;1940\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAriello K, Tan H, Soliman H (2021) Narrative review of neurocognitive and quality of life tools used in brain metastases trials. Ann Palliat Med 10:92335\u0026ndash;92935. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.21037/APM-20-1036\u003c/span\u003e\u003cspan address=\"10.21037/APM-20-1036\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClarke R, Hannan A, Chow H et al (2024) An exploration of intensive care unit patents\u0026rsquo; experiences of the Addenbrooke\u0026rsquo;s Cognitive Examination (ACE-III) as a screening tool for cognitive functioning at different points in recovery from critical illness. \u003cdiv class=\"ExternalRefDOI\"\u003ehttps://doi.org/101177/17511437241241242\u003c/div\u003e. https://doi.org/10.1177/17511437241241242\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMathuranath PS, Hodges JR, Mathew R et al (2004) Adaptation of the ACE for a Malayalam speaking population in southern India. Int J Geriatr Psychiatry 19:1188\u0026ndash;1194. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/GPS.1239\u003c/span\u003e\u003cspan address=\"10.1002/GPS.1239\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEORTC QLQ-C30 | EORTC \u0026ndash; Quality of Life \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://qol.eortc.org/questionnaires/core/eortc-qlq-c30/\u003c/span\u003e\u003cspan address=\"https://qol.eortc.org/questionnaires/core/eortc-qlq-c30/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 9 Nov 2024\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrain Cancer (update of QLQ-BN20) | EORTC \u0026ndash; Quality of Life. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://qol.eortc.org/questionnaire/bn20-update/\u003c/span\u003e\u003cspan address=\"https://qol.eortc.org/questionnaire/bn20-update/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Accessed 9 Nov 2024\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang EL, Wefel JS, Hess KR et al (2009) Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial. Lancet Oncol 10:1037\u0026ndash;1044. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S1470-2045(09)70263-3\u003c/span\u003e\u003cspan address=\"10.1016/S1470-2045(09)70263-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVan Grinsven EE, Nagtegaal SHJ, Verhoeff JJC, Van Zandvoort MJE (2021) The Impact of Stereotactic or Whole Brain Radiotherapy on Neurocognitive Functioning in Adult Patients with Brain Metastases: A Systematic Review and Meta-Analysis. Oncol Res Treat 44:622\u0026ndash;636. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000518848\u003c/span\u003e\u003cspan address=\"10.1159/000518848\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Grinsven EE, Cialdella F, Verhoeff JJC et al (2023) Different profiles of neurocognitive functioning in patients with brain metastases prior to brain radiotherapy. Psychooncology 32:1752\u0026ndash;1761. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/PON.6229\u003c/span\u003e\u003cspan address=\"10.1002/PON.6229\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanding EP, Leng XI, Kritchevsky SB, Craft S (2020) Association Between Physical Performance and Cognitive Function in Older Adults Across Multiple Studies: A Pooled Analysis Study. Innov Aging 4:1\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/GERONI/IGAA050\u003c/span\u003e\u003cspan address=\"10.1093/GERONI/IGAA050\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDixon A, Porter S, Suhrie K et al (2022) Predicting daily functioning with the modified Telephone Interview for Cognitive Status. Aging Clin Exp Res 34:1267\u0026ndash;1274. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/S40520-022-02081-4\u003c/span\u003e\u003cspan address=\"10.1007/S40520-022-02081-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrayn-Deckel N, Presaizen K, Kalron A (2024) Cognitive status is associated with performance of manual wheelchair skills in hospitalized older adults. Disabil Rehabil Assist Technol 19:24\u0026ndash;29. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/17483107.2022.2060353\u003c/span\u003e\u003cspan address=\"10.1080/17483107.2022.2060353\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAminoff EM, Kveraga K, Bar M (2013) The role of the parahippocampal cortex in cognition. Trends Cogn Sci 17:379\u0026ndash;390. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/J.TICS.2013.06.009\u003c/span\u003e\u003cspan address=\"10.1016/J.TICS.2013.06.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTeplyshova AM, Shalimanova EV (2023) Cognitive impairment in temporal lobe epilepsy. Epilepsy paroxysmal conditions 14:355\u0026ndash;361. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.17749/2077-8333/EPI.PAR.CON.2022.134\u003c/span\u003e\u003cspan address=\"10.17749/2077-8333/EPI.PAR.CON.2022.134\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchmidbauer V, Nenning KH, Schwarz M et al (2022) Imaging visuospatial memory in temporal lobe epilepsy-Results of an fMRI study. PLoS ONE 17. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1371/JOURNAL.PONE.0264349\u003c/span\u003e\u003cspan address=\"10.1371/JOURNAL.PONE.0264349\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGunia A, Moraresku S, Janča R et al (2024) The brain dynamics of visuospatial perspective-taking captured by intracranial EEG. NeuroImage 285:120487. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/J.NEUROIMAGE.2023.120487\u003c/span\u003e\u003cspan address=\"10.1016/J.NEUROIMAGE.2023.120487\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie C, Zhong D, Zhang Y et al (2023) Prevalence and risk factors of cognitive impairment in Chinese patients with hypertension: a systematic review and meta-analysis. Front Neurol 14:1271437. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/FNEUR.2023.1271437/BIBTEX\u003c/span\u003e\u003cspan address=\"10.3389/FNEUR.2023.1271437/BIBTEX\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSuvvari TK (2024) Exploring the association between hypertension and cognitive impairment: Evidence-based insights. Chronic Dis Transl Med 10:153\u0026ndash;155. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/CDT3.95\u003c/span\u003e\u003cspan address=\"10.1002/CDT3.95\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaggeroer CE, Cambronero FE, Savan NA et al (2024) Basic Mechanisms of Brain Injury and Cognitive Decline in Hypertension. Hypertension 81:34\u0026ndash;44. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1161/HYPERTENSIONAHA.123.19939\u003c/span\u003e\u003cspan address=\"10.1161/HYPERTENSIONAHA.123.19939\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWestover KD, Travis Mendel J, Dan T et al (2020) Phase II trial of hippocampal-sparing whole brain irradiation with simultaneous integrated boost for metastatic cancer. Neuro Oncol 22:1831\u0026ndash;1839. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/NEUONC/NOAA092\u003c/span\u003e\u003cspan address=\"10.1093/NEUONC/NOAA092\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown PD, Gondi V, Pugh S et al (2020) Hippocampal avoidance during whole-brain radiotherapy plus memantine for patients with brain metastases: Phase III trial NRG oncology CC001. J Clin Oncol 38:1019\u0026ndash;1029. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1200/JCO.19.02767/SUPPL_FILE/PROTOCOL_JCO.19.02767.PDF\u003c/span\u003e\u003cspan address=\"10.1200/JCO.19.02767/SUPPL_FILE/PROTOCOL_JCO.19.02767.PDF\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown PD, Jaeckle K, Ballman KV et al (2016) Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial. JAMA 316:401\u0026ndash;409. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/JAMA.2016.9839\u003c/span\u003e\u003cspan address=\"10.1001/JAMA.2016.9839\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Grinsven EE, Cialdella F, Verhoeff JJC et al (2023) Different profiles of neurocognitive functioning in patients with brain metastases prior to brain radiotherapy. Psychooncology 32:1752\u0026ndash;1761. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/PON.6229\u003c/span\u003e\u003cspan address=\"10.1002/PON.6229\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Addenbrooke's Cognitive Examination (ACE), Brain metastases, EORTC QLQ-C30, EORTC QLQ-BN20, Cognitive impairment, Neurocognitive assessment, Neurocognitive profiling, Quality of life (QoL), Predictive factors, Radiation therapy","lastPublishedDoi":"10.21203/rs.3.rs-5741939/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5741939/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003eTo evaluate neurocognitive function and quality of life (QoL) scores in brain metastasis (BM) patients as potential indicators for optimizing therapeutic interventions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003eNeurocognitive function and QoL scores were collected from a prospective randomized trial (CTRI/2022/01/039599) involving BM patients (n=130). Neurocognitive function was assessed using the Addenbrooke's Cognitive Examination (ACE), and QoL was measured using EORTC QLQ-C30 and BN20 questionnaires prior to radiation therapy (RT). Predictors of neurocognitive decline and QoL outcomes were identified through descriptive and regression analyses to inform intervention strategies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003eAt baseline, mean ACE scores were 75.19 ± 18.67. Among patients, 60% had normal cognitive function (ACE ≥ 75), while 28.5%, 6.2%, and 5.4% exhibited mild (1 SD decline), moderate (2 SDs decline), and severe cognitive impairment (ACE \u0026lt; 37), respectively. Significant predictors of impairment included poor performance status (ECOG 2; OR = 52.08, p \u0026lt; 0.001), education below graduation (OR = 0.002, p = 0.03), hypertension (OR = 52.08, p = 0.02), and lesions in the left temporal (OR = 71.4, p = 0.04) and occipital lobes (p = 0.03). Baseline mean global QoL score was 56.5 ± 32.5, with functional domain scores ≤60 in all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003eAt baseline, 60% of BM patients demonstrated normal cognition, while the remaining exhibited impairments, predominantly in memory, verbal fluency, and visuospatial abilities. Severe cognitive impairment correlated with poor ECOG status, lower education, hypertension, and left temporal lesions. Incorporating neurocognitive and QoL assessments into routine practice may aid in personalized intervention planning.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration number: CTRI/2022/01/039599\u003c/strong\u003e\u003c/p\u003e","manuscriptTitle":"Neurocognitive and QoL Profiles as a Tools for Informed Decisions in Brain Metastasis Management: Analysis from A Prospective Randomized Placebo-Controlled Trial (CTRI/2022/01/039599).","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-06 09:17:45","doi":"10.21203/rs.3.rs-5741939/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"56ce96dc-5cf4-472c-9259-11b40774950d","owner":[],"postedDate":"January 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-22T23:38:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-06 09:17:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5741939","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5741939","identity":"rs-5741939","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}