Challenges in Neuropsychological Improvement After Shunt Surgery for Idiopathic Normal Pressure Hydrocephalus

Challenges in Neuropsychological Improvement After Shunt Surgery for Idiopathic Normal Pressure Hydrocephalus | 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 Challenges in Neuropsychological Improvement After Shunt Surgery for Idiopathic Normal Pressure Hydrocephalus Ondřej Rýdlo, Adéla Bubeníková, Petr Skalický, Klára Häcklová, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6802703/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 Objectives We sought to analyze cognitive performance and depressive symptoms of Idiopathic Normal Pressure Hydrocephalus (iNPH) patients three months after the shunt surgery. We assembled different neuropsychological tests into specific cognitive domains: Verbal Memory, Non-Verbal Memory, Executive Functions, Visuo-spatial Abilities, Language and Psychomotor Pace. Methods INPH patients underwent a complex neuropsychological assessment prior to the shunt surgery and three months after. We compared the results of cognitive performance before and after the shunt surgery in order to assess the effect of the surgery on cognition and depressive symptoms. Additionally, we compared the post-surgical cognitive performance of iNPH patients to age, sex- and education-matched group of healthy controls to see whether the iNPH patients reached the performance level of the normal population. Results Out of the 126 patients for suspected iNPH 33 patients met all the inclusion criteria. Additionally, we used 71 healthy controls. For the analysis of cognitive performance change after shunt surgery we found significant improvement in tests covering Verbal Memory ( p = 0.033, p = 0.043 and p = 0.007) and Psychomotor Pace ( p = 0.003). We found mixed results for tests covering Executive functions ( p = 0.890, p = 0.070, p = 0.002). We found no improvement for the tests covering Non-Verbal Memory ( p = 0.100, p = 0.297), Language ( p = 0.916, p = 0.498) and Visuo-spatial Abilities ( p = 0.483). We also found improvement in depressive symptoms ( p = 0.020). For the analysis of the 3 months after surgery iNPH patients cognitive performance and control group cognitive performance we found all neuropsychological tests to significantly differ ( p < 0.001). Conclusion Shunt surgery appears to have a positive effect on the neuropsychological performance of patients with iNPH. However, the improvement is limited. First, the effect does not appear to be comprehensive but rather restricted to certain neuropsychological domains. We observed improvements in the Verbal Memory and Psychomotor Pace domains, while results for Executive Functions were mixed—suggesting a positive effect on patients' ability to plan but no effect on their ability to shift. No effects were found for Visuospatial Abilities or Language. Second, the improvement appears to be limited in magnitude. Although overall performance improves three months after surgery, it still does not reach the level of healthy individuals. Nevertheless, the absence of worsening might also be seen as a positive effect. Interestingly, depressive symptoms followed a similar pattern to cognitive functioning before and after surgery. We found that shunt surgery significantly alleviated depressive symptoms. normal pressure hydrocephalus neuropsychology cognitive decline cognitive domain depression Introduction Idiopathic normal pressure hydrocephalus (iNPH) is a condition characterized typically by the Hakim's triad: incontinence, gait disturbance and cognitive decline (Nakajima et al., 2021 ). It predominantly affects the elderly, with a prevalence of 1.4–3.7%, increasing with age (Andersson et al., 2019 ; Shprecher et al., 2008 ). The most prominent symptom is gait disturbance, occurring approximately in 90–100% of patients, followed by the cognitive decline occurring in 78–98% of patients (Agerskov et al., 2018 ; Nakajima et al., 2021 ). Cognitive decline in iNPH significantly impacts patients' quality of life and functional independence. Ventriculoperitoneal shunting (VPS) is the standard treatment aimed at restoring cerebrospinal fluid (CSF) dynamics, yet the extent and mechanisms of cognitive improvement remain under investigation. Cognitive assessment in iNPH often relies on global screening tools such as the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), both of which show postoperative improvement (Hülser et al., 2022 ; Xiao et al., 2022 ). The overall cognitive improvement may correlate with the depth and nature of cognitive deficits before surgery (Thomas et al., 2005 ). However, regardless of the severity of the cognitive deficit, the shorter the time since the onset of symptoms, the greater the expected postoperative improvement in cognitive performance (Xiao et al., 2022 ). While global cognitive screening is useful, it provides limited insight into the specific neuropsychological profile of iNPH patients. Tools like the MoCA rely on abbreviated versions of comprehensive tests, often missing subtle domain-specific deficits. As a result, screenings alone cannot capture which cognitive domains are most affected or how they change post-treatment. Incorporating detailed neuropsychological assessment can therefore enhance diagnosis, treatment planning, and monitoring of cognitive changes. The most affected cognitive domains in iNPH are executive functions (EFs), memory, and psychomotor pace (PP), with attention also showing significant impairment (Rýdlo et al., 2024 ; Xiao et al., 2022 ). On the other hand, there is inconclusiveness regarding visuo-spatial abilities (Bugalho et al., 2014 ; Xiao et al., 2022 ) and the language seems to be mostly spared (Saito et al., 2011 ). EF deficits are among the most studied and appear to improve after shunting, though findings remain inconsistent (Bugalho et al., 2014 ; Devito et al., 2005 ; Hellström et al., 2008 ; Katzen et al., 2011 ; Laidet et al., 2015 ; Solana et al., 2012 ). While some studies report significant gains, others only observe statistical trends (Hülser et al., 2022 ). Memory dysfunction, particularly in verbal and non-verbal long-term recall, also improves postoperatively, suggesting a role for CSF restoration in cognitive recovery (Rýdlo et al., 2024 ). There is a significant improvement after shunt surgery in long term memory, both verbal (Hellström et al., 2008 ; Solana et al., 2012 ) and non-verbal (Skalický et al., 2022 ; Thomas et al., 2005 ). Attention, closely linked to EFs, seems more impaired in iNPH compared to Alzheimer’s disease, and some studies suggest it improves after surgery, further supporting the need for targeted cognitive rehabilitation. (Hülser et al., 2022 ; Ogino et al., 2006 ; Rýdlo et al., 2024 ). Despite these findings, the literature on detailed cognitive profiling in iNPH remains limited. A more precise understanding of cognitive deficits before and after shunting is crucial for refining the diagnostic process, differentiating dementia subtypes, and optimizing patient management. Future research should prioritize comprehensive neuropsychological assessments to enhance treatment strategies and improve patient outcomes. Materials and Methods Participants Between 2018 and 2021, a total of 126 patients with suspected iNPH were evaluated at the Department of Neurosurgery and Neuro-oncology. They underwent a comprehensive diagnostic protocol, including clinical, psychological, imaging, and functional assessments. To be included in the study, patients had to meet the following criteria: (1) symptom onset lasting at least three months, (2) an Evans’ index greater than 0.3, (3) gait disturbance along with at least one additional symptom from Hakim’s triad, and (4) no other known condition that could explain their symptoms. Admitted patients underwent lumbar infusion test (LIT) and CSF drainage for 120 hours. After that, the clinical evaluation was repeated. All patients improving 15% on the Dutch Gait Scale and imaging criteria were evaluated as probable iNPH and consequently underwent shunt surgery. If the criteria were not met, the patients were referred for further outpatient surveillance. Out of the 126 patients admitted for suspected iNPH, 56 patients fulfilled given diagnostic criteria and had been included in this study. Out of the 56 participants included in the study from neurosurgical perspective, we excluded all participants with GDS-15 score 10 or higher (n = 3), which is an indication of severe depressive symptoms that can interfere with cognitive abilities (Shin et al., 2019 ). Then, we excluded all participants with a MoCA score lower than 18 (n = 20), which is an artificial but suggested border that is used for controlling the severity of cognitive decline (Milani et al., 2018 ; Yeung et al., 2020 ). In summary, the results of 33 experimental patients were analyzed. The neuropsychological assessment was conducted in a standard clinical setting by a trained neuropsychologist that did not know the results of the other functional testing. The testing took place before shunt implantation and 3 months after the surgery. The control group consisted of 71 healthy probands who were derived from the National Normative Study of Cognitive Determinants of Healthy Aging, NANOK (Štěpánková et al., 2015 ). This sample was adjusted to the experimental group by age, education and gender. Neuropsychological Battery We used a complex neuropsychological battery that was created by trained neuropsychologists with regard to the iNPH patient cognitive profile. The battery evaluated multiple cognitive domains. For EFs we used the Trail Making test in form B (Bezdicek et al., 2017 ), the Block Design subtest of Wechsler Adult Intelligence Scale (Černochová et al., 2010 ), the Rey-Osterrieth Complex Figure Test (Drozdová et al., 2015 ) and the Letter Fluency (czech standardized version with letters N, K, P, Nikolai et al., 2015 ). For vM we used the results of the Auditory Verbal Learning Test (AVLT; score for I-V trial, VI trial and 30 min delay recall, Frydrychová et al., 2018 ). Similarly, we used the ROCF reproduction (3 min) and 30 min delay recall for Non-verbal Memory. We furthermore assessed Psychomotor Pace with TMT version A (Bezdicek et al., 2017 ) and Language with Category fluency (czech standardized version for animals and vegetables, Nikolai et al., 2015 ). Additionally, we used the Montreal Cognitive Assessment (Kopecek et al., 2017 ; Nasreddine et al., 2005 ) as a global screening of cognitive performance, which includes subtests assessing the patient's visuoconstructional, executive functions, memory, attention, and verbal functions. Lastly, we assessed depressive symptoms with Geriatric Depression Scale (GDS-15) with fifteen items, a shortened version of the original 30-items questionnaire (Yesavage et al., 1982 ). Statistical Analysis For comparing the control group with the 3 months post-shunt NPH group, the appropriate statistical test was chosen based on the normality and homogeneity of variance assumptions. The normality of the data was analyzed with the Kolmogorov-Smirnov test. An Independent Samples t-Test was used for normally distributed data with equal variances. Within the NPH group, paired t-tests were used to compare pre-shunt and post-shunt (3 months) scores. The magnitude of change was evaluated according to Cohen’s criteria (0.5 = large, 0.3 = medium, 0.1 = small). Statistical significance will generally be considered at a threshold of p < 0.050. All statistical analyses were conducted with Jamovi statistical software (v2.3, The Jamovi Project 2022, https://www.jamovi.org/ ). Results Cognitive Performance Before and After Shunt Surgery We analyzed cognitive performance in iNPH patients pre- and three months post-shunt surgery. Paired-samples t-test showed no significant change in MoCA scores (21.33 ± 2.35 vs. 21.35 ± 4.36, p < 0.001). However, vM improved significantly: AVLT I-V (24.7 ± 8.68 vs. 29.11 ± 8.72, p = 0.033), AVLT VI (2.83 ± 2.24 vs. 3.66 ± 2.18, p = 0.043), and AVLT VII (2.31 ± 2.36 vs. 3.62 ± 2.82, p = 0.007). nvM did not significantly improve: ROCF 3M (9.36 ± 6.11 vs. 11.26 ± 5.72, p = 0.100) and ROCF 30M (10.02 ± 5.92 vs. 11.24 ± 4.84, p = 0.297). EFs showed mixed results. While TMT B (200.48 ± 74.17 vs. 197 ± 112.72, p = 0.890) and NKP (25.83 ± 10.19 vs. 28.72 ± 10.48, p = 0.070) did not reach significance, the BDT improved significantly (20.82 ± 7.82 vs. 25.04 ± 8.34, p = 0.002). PP significantly improved, with TMT A scores decreasing (86.55 ± 34.09 vs. 75.01 ± 29.96, p = 0.030). VA and LA did not change significantly: ROCF-copy (27.09 ± 7.54 vs. 27.95 ± 6.26, p = 0.483), Animals (14.79 ± 5.49 vs. 14.90 ± 4.50, p = 0.916), and Vegetables (8.14 ± 2.53 vs. 8.45 ± 2.34, p = 0.498). Depressive symptoms, assessed via GDS-15, significantly decreased (4.72 ± 2.76 vs. 3.62 ± 2.38, p = 0.020). Table 1 Cognitive Performance of iNPH Patients Before and After Shunt Surgery. Cognitive Domain Test Pre-Intervention (M ± SD) Post-Intervention (M ± SD) t-value p-value Effect Size (d) Global Cognition MoCA 21.33 ± 2.35 21.35 ± 4.36 -0.02 < 0.001 0.004 Verbal Memory (vM) AVLT I-V 24.7 ± 8.68 29.11 ± 8.72 -2.26 .033 -0.434 AVLT VI 2.83 ± 2.24 3.66 ± 2.18 -2.12 0.043 -0.393 AVLT VII 2.31 ± 2.36 3.62 ± 2.82 -2.93 0.007 -0.544 Non-Verbal Memory (nvM) ROCF 3M 9.36 ± 6.11 11.26 ± 5.72 -1.70 0.100 -0.316 ROCF 30M 10.02 ± 5.92 11.24 ± 4.84 -1.07 0.297 -0.213 Executive Functions (EFs) TMT B 200.48 ± 74.17 197 ± 112.72 0.14 0.890 0.030 NKP 25.83 ± 10.19 28.72 ± 10.48 -1.88 0.070 -0.349 BDT 20.82 ± 7.82 25.04 ± 8.34 -3.51 0.002 -0.663 Psychomotor Pace (PP) TMT A 86.55 ± 34.09 75.01 ± 29.96 2.29 0.030 0.425 Visuospatial Abilities (VA) ROCF-copy 27.09 ± 7.54 27.95 ± 6.26 -0.71 0.483 0.134 Language (LA) Animals 14.79 ± 5.49 14.90 ± 4.50 -0.11 0.916 -0.020 Vegetables 8.14 ± 2.53 8.45 ± 2.34 -0.69 0.498 -0.127 Depressive Symptoms GDS-15 4.72 ± 2.76 3.62 ± 2.38 2.47 0.020 0.458 MoCA - Montreal Cognitive Assessment, AVLT - Auditory Verbal Learning Test, ROCF - Rey-Osterrieth Complex Figure, TMT - Trail Making Test, GDS-15 - Geriatric Depression Scale 15 items Comparison Between iNPH Patients and Healthy Controls To assess post-surgery cognitive outcomes, we compared iNPH patients (71.3 ± 5.2 years, 69.7% male) with healthy controls (72.7 ± 4.8 years, 62% male, Table XX). The groups did not significantly differ in demographics. Independent t-tests showed significant cognitive differences favoring the control group (Table 3 ). MoCA, AVLT I-V, AVLT VI, AVLT VII, ROCF 3M, ROCF 30M, TMT B, NKP, Animals, TMT A (all p < 0.001), ROCF Copy (p = 0.006), and GDS-15 (p = 0.004) all showed significant differences, with iNPH patients performing worse. Table 2 Descriptives Group n Age (M ± SD) Male (%) iNPH 30 71.3 ± 5.2 69.7% Control 71 72.7 ± 4.8 62% Table 3 Comparison Between iNPH Patients and Healthy Controls. Test t-value p-value Effect Size (d) MoCA 6.71 < 0.001 1.46 AVLT I-V 6.54 < 0.001 1.44 AVLT VI 8.31 < 0.001 1.83 AVLT VII 5.84 < 0.001 1.29 ROCF 3M 4.20 < 0.001 0.93 ROCF 30M 3.50 < 0.001 0.80 TMT B -4.14 < 0.001 -0.978 NKP 5.52 < 0.001 1.216 Animals 6.22 < 0.001 1.371 TMT A -4.54 < 0.001 -1.00 ROCF Copy 2.79 0.006 0.615 GDS-15 -2.93 0.004 -0.645 MoCA - Montreal Cognitive Assessment, AVLT - Auditory Verbal Learning Test, ROCF - Rey-Osterrieth Complex Figure, TMT - Trail Making Test, NKP - Letter fluency test, GDS-15 - Geriatric Depression Scale 15 items Discussion We examined a detailed neuropsychological profile of patients with iNPH and its development after shunt surgery. We applied a complex neuropsychological battery before shunt surgery and three months after shunt surgery to see mid-term effects of the treatment. We used a control group of healthy individuals to assess the cognitive performance of iNPH patients 3 months after shunt surgery in order to assess magnitude of change and determine normality of cognitive performance. Utilizing a multidimensional neuropsychological battery administered both prior to and three months following shunting, and contrasting patient performance against a matched healthy control group, we aimed to delineate the trajectory of cognitive changes and their clinical significance. The most compelling and consistent finding was the significant postoperative improvement in vM, which, although still below normative levels, demonstrated the greatest relative gain among all evaluated cognitive domains. This result underscores the centrality of vM as a surgery-sensitive domain in iNPH and supports the notion that specific aspects of memory—especially those dependent on fronto-subcortical connectivity—are amenable to intervention via CSF diversion. (Xiao et al., 2022 ). Our recent study suggests that the memory impairment might be uneven in its verbal and non-verbal parts (Rýdlo et al., 2024 ). nvM, in contrast to vM, remained significantly impaired three months postoperatively and did not exhibit measurable improvement. This persistence of dysfunction despite relatively milder baseline impairment raises several interpretations: it is possible that nvM, due to either different neural circuitry or structural damage, possesses a higher threshold for recovery or exhibits a more protracted response to CSF modulation. Alternatively, nvM-related deficits may reflect more permanent neuropathological alterations. While some longitudinal studies report delayed cognitive improvement—most notably at the 12-month mark— (Büyükgök et al., 2021 ) others suggest a transient or even absent effect of shunting on cognition, highlighting the variability of neuropsychological outcomes in this population (Lilja-Lund et al., 2023 ). Importantly, the distinctive effect on vM and nvM may serve as a useful tool in clinical differentiation, particularly in distinguishing iNPH from Alzheimer’s disease (AD), where both memory systems are often compromised due to hippocampal atrophy. (Picascia, 2015 ). In our study, the relative preservation of nvM in iNPH patients could constitute a potential diagnostic indicator, bolstering the clinical utility of memory subdomain profiling in the context of neurodegenerative differential diagnosis. This aligns with earlier literature suggesting that AD is typified by a more global mnemonic disruption, and reinforces the need for targeted neuropsychological batteries in clinical assessments. The domain of EFs yielded mixed results. Contrary to expectations and previous findings, our cohort did not demonstrate improvement in set-shifting ability, as assessed via the TMT-B. This result may suggest that certain executive functions are less responsive to the effects of shunting, or that inter-individual variability masks group-level changes (Duinkerke et al., 2004 ; Mataro et al., 2006 ; Thomas et al., 2005 ). The absence of improvement in TMT-B could also reflect limitations in sensitivity of this task or high baseline variability in performance. Similarly, verbal fluency—a task also associated with shifting and executive control—exhibited a positive trend that failed to reach statistical significance (p = 0.070). In contrast, performance on the BDT, a task reflecting visuo-constructive planning and execution, improved markedly, with the largest effect size observed across all assessments (d = -0.660). This finding suggests that executive domains reliant on structured planning rather than rapid cognitive flexibility may be more susceptible to recovery following CSF diversion. Given that BDT engages strategic organization, working memory, and spatial planning—processes mediated by dorsolateral prefrontal and parietal regions—these results may point to a more selective restoration of frontoparietal networks post-surgery (Ogino et al., 2006 ). Psychomotor processing speed, assessed via TMT-A, significantly improved after shunt surgery, a finding in close alignment with the broader literature that characterizes psychomotor slowing as a core cognitive feature of iNPH (Xiao et al., 2022 ). The improvement in this domain strengthens the hypothesis that psychomotor speed serves as a sensitive index of functional change and therapeutic responsiveness. Although some earlier reports, such as those by Savolainen et al. ( 2002 ) noted no significant change in TMT-A scores, these inconsistencies may arise from methodological differences, variable follow-up durations, or heterogeneous patient cohorts. It is also noteworthy that subjective clinical improvement may not always be captured by psychometric indices, underscoring the importance of triangulating data sources in the assessment of surgical efficacy. In the domains of VA and LA, no significant postoperative changes were observed. Importantly, the VA domain appeared to be among the least impaired both pre- and postoperatively relative to healthy controls. This may reflect a floor effect in recovery: domains that are relatively intact at baseline may lack the functional deficit necessary to elicit measurable improvement. Alternatively, these findings may point to the limited sensitivity of the employed neuropsychological instruments in detecting subtle or subclinical changes in these functions. It remains to be investigated whether more fine-grained or dynamic assessments might capture such changes more accurately. On the other hand, the cognitive capabilities of patients are typically limited and neuropsychological protocol should strive for maximum sensitivity and should minimize overload of patients. Our research and above mentioned scope of literature supports overall positive neuropsychological outcomes of shunt surgery. Nevertheless, to some degree the positive outcome is controversial and appears to vary among individuals and also vary in time after the surgery. In fact, Solana et al. ( 2012 ) found that when assessed as a group, the positive effect in neuropsychological outcomes is visible, however, when assessed individually less than 50% of the patients can be classified as improved. This poses a significant challenge for the future. We now accept the overall benefit of shunt surgery on cognitive performance for iNPH patients, however we know little about individual specific factors that could predict or contradict the response in this clinical feature and it is of high importance to develop sufficient diagnostic processes not only for the diagnosis itself but also for the management of the patient’s care and patient’s expectations. Beyond cognitive outcomes, our study identified a noteworthy alleviation of depressive symptoms following shunt surgery. Although depressive symptoms remained elevated in comparison to healthy adults, the reduction from preoperative levels was statistically and clinically significant. This contrasts with previous findings, such as those by Israelsson et al. ( 2016 ) who reported sustained depressive symptomatology postoperatively but did not assess pre-shunt affective status. Our data suggest that, at least in the early postoperative phase, CSF diversion may confer a beneficial effect on mood. Given the bidirectional relationship between mood and cognition, the improvement in depressive symptoms may not only reflect direct affective benefit but may also secondarily enhance cognitive performance, motivation, and quality of life. The persistence of subclinical depression, however, warrants ongoing monitoring and further investigation into its neurobiological underpinnings and long-term evolution. Another critical methodological observation arising from our study is the inadequacy of global cognitive screening tools—specifically the MoCA—in detecting postoperative cognitive changes. Despite the documented improvements revealed by the comprehensive neuropsychological battery, MoCA scores did not reflect these gains. This highlights a major limitation in using brief cognitive screening instruments in the postoperative evaluation of iNPH patients and argues strongly for the adoption of domain-specific assessments as standard practice in both clinical and research settings. Study Strengths and Limitations Several limitations of the present study merit discussion. The diagnostic accuracy of preoperative CSF testing (e.g., lumbar infusion and drainage procedures) remains imperfect, potentially resulting in the exclusion of patients who might have benefitted from shunting. Although response to shunting is the gold standard for definitive diagnosis, this dependency introduces a degree of selection bias inherent to all iNPH studies. Furthermore, the three-month follow-up period, while clinically standard, limits conclusions regarding the durability and temporal progression of cognitive changes. Longer-term assessments are necessary to capture delayed or regressive cognitive trajectories. The neuropsychological battery, although comprehensive and tailored to patient tolerability, did not cover all cognitive domains in equal depth, and several domains were represented by only one test, which constrains interpretative robustness. The use of raw scores, while preserving ecological validity, may limit cross-study comparability, though it mitigates transformation-induced distortion. The sample size, while adequate for group-level inference, restricts generalizability and precludes finer-grained subgroup analyses. We did not stratify patients based on cognitive reserve, functional capacity, or symptom duration, all of which may modulate responsiveness to surgical intervention and should be considered in future studies. Additionally, estimating symptom onset retrospectively via caregiver reports introduces a further layer of uncertainty (Krahulik et al., 2020 ). Nevertheless, the inclusion of age-, sex-, and education-matched healthy controls strengthens the interpretive validity of our findings, particularly in assessing the normalization—or lack thereof—of postoperative cognitive performance. While this design provides a valuable point of reference, our findings must ultimately be contextualized within the broader heterogeneity of iNPH populations. Indeed, as highlighted by Solana et al. ( 2012 ), group-level improvements may obscure considerable intra-individual variability, with fewer than half of patients showing significant cognitive gains when assessed individually. This presents a formidable clinical challenge: while the general benefit of shunt surgery is increasingly recognized, little is known about the predictors of individual cognitive outcomes. There remains an urgent need to develop prognostic models incorporating neuropsychological, neuroimaging, and biomarker data to improve patient selection, inform surgical decision-making, and manage postoperative expectations. Conclusion The shunt surgery seems to positively influence the neuropsychological performance of patients with iNPH. The most compelling and consistent finding was the significant postoperative improvement in vM, which, although still below normative levels, demonstrated the greatest relative gain among all evaluated cognitive domains. This result underscores the centrality of vM as a surgery-sensitive domain in iNPH and supports the notion that specific aspects of memory—especially those dependent on fronto-subcortical connectivity—are amenable to intervention via CSF diversion. Along with vM, PP also significantly improved, which strengthens the hypothesis that psychomotor speed serves as a sensitive index of functional change and therapeutic responsiveness. Interestingly, mixed results were found for EFs, that contrary to prior findings did not demonstrate improvement in set-shifting ability but improved part of the EFs reliant on structured planning rather than rapid cognitive flexibility. Visuospatial abilities and language remained unimproved by the shunt surgery. It is also noteworthy that none of the cognitive domains declined during the study period, and the absence of deterioration can be interpreted as a positive outcome in itself. Beyond cognitive outcomes, our study identified an alleviation of depressive symptoms following shunt surgery. Although depressive symptoms remained elevated in comparison to healthy adults, the reduction from preoperative levels was statistically and clinically significant. Declarations Ethics approval and consent to participate This study was approved by the ethics board of the Military University Hospital Prague. Informed consent was obtained from all patients before their inclusion into the database and following procedures. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors have no relevant financial or non-financial interests to disclose. Funding This work was supported by the Ministry of Health of the Czech Republic number NU23-04-00551. Authors' contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ondřej Rýdlo, Adéla Bubeníková, Petr Skalický, and Ondřej Bradáč. The first draft of the manuscript was written by Ondřej Rýdlo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Agerskov S, Hellström P, Andrén K, Kollén L, Wikkelsö C, Tullberg M. 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Katzen H, Ravdin LD, Assuras S, Heros R, Kaplitt M, Schwartz TH, Fink M, Levin BE, Relkin NR. Postshunt Cognitive and Functional Improvement in Idiopathic Normal Pressure Hydrocephalus. Neurosurgery. 2011;68(2):416–9. https://doi.org/10.1227/NEU.0b013e3181ff9d01 . Kopecek M, Stepankova H, Lukavsky J, Ripova D, Nikolai T, Bezdicek O. Montreal cognitive assessment (MoCA): Normative data for old and very old Czech adults. Appl Neuropsychology: Adult. 2017;24(1):23–9. https://doi.org/10.1080/23279095.2015.1065261 . Krahulik D, Vaverka M, Hrabalek L, Hampl M, Halaj M, Jablonsky J, Langova K. Ventriculoperitoneal shunt in treating of idiopathic normal pressure hydrocephalus—Single-center study. Acta Neurochir. 2020;162(1):1–7. https://doi.org/10.1007/s00701-019-04135–5 . Laidet M, Herrmann FR, Momjian S, Assal F, Allali G. Improvement in executive subfunctions following cerebrospinal fluid tap test identifies idiopathic normal pressure hydrocephalus from its mimics. Eur J Neurol. 2015;22(12):1533–9. https://doi.org/10.1111/ene.12779 . Lilja-Lund O, Maripuu M, Kockum K, Andersson J, Lindam A, Nyberg L, Laurell K. Longitudinal neuropsychological trajectories in idiopathic normal pressure hydrocephalus: A population–based study. BMC Geriatr. 2023;23(1):29. https://doi.org/10.1186/s12877-023-03747-y . Mataro M, Matarin M, Poca MA, Pueyo R, Sahuquillo J, Barrios M, Junque C. Functional and magnetic resonance imaging correlates of corpus callosum in normal pressure hydrocephalus before and after shunting. J Neurol Neurosurg Psychiatry. 2006;78(4):395–8. https://doi.org/10.1136/jnnp.2006.096164 . Milani SA, Marsiske M, Cottler LB, Chen X, Striley CW. Optimal cutoffs for the Montreal Cognitive Assessment vary by race and ethnicity. Alzheimer’s Dementia: Diagnosis Assess Disease Monit. 2018;10(1):773–81. https://doi.org/10.1016/j.dadm.2018.09.003 . Nakajima M, Yamada S, Miyajima M, Ishii K, Kuriyama N, Kazui H, Kanemoto H, Suehiro T, Yoshiyama K, Kameda M, Kajimoto Y, Mase M, Murai H, Kita D, Kimura T, Samejima N, Tokuda T, Kaijima M, Akiba C. Guidelines for Management of Idiopathic Normal Pressure Hydrocephalus (Third Edition): Endorsed by the Japanese Society of Normal Pressure Hydrocephalus. Neurologia medico-chirurgica. 2021;61(2):63–97. https://doi.org/10.2176/nmc.st.2020–0292 . … The research committee of idiopathic normal pressure hydrocephalus. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment. J Am Geriatr Soc. 2005;53(4):695–9. https://doi.org/10.1111/j.1532–5415.2005.53221.x . Nikolai T, Štěpánková H, Michalec J, Bezdíček O, Horáková K, Marková H, Kopeček M. Testy verbální fluence, česká normativní studie pro osoby vyššího věku. Česká Slovenská Neurologie Neurochirurgie. 2015;78/111(3):292–9. Ogino A, Kazui H, Miyoshi N, Hashimoto M, Ohkawa S, Tokunaga H, Ikejiri Y, Takeda M. Cognitive Impairment in Patients with Idiopathic Normal Pressure Hydrocephalus. Dement Geriatr Cogn Disord. 2006;21(2):113–9. https://doi.org/10.1159/000090510 . Picascia M. A review of cognitive impairment and differential diagnosis in idiopathic normal pressure hydrocephalus. Funct Neurol. 2015. https://doi.org/10.11138/FNeur/2015.30.4.217 . Rýdlo O, Bubeníková A, Häcklová K, Skalický P, Leško R, Ebelová A, Netuka D, IIIrd VB, Beneš V, Bradáč O. Comparison of decline in different cognitive domain in patients with normal pressure hydrocephalus. Neurosurg Rev. 2024;47(1):167. https://doi.org/10.1007/s10143-024-02410–3 . Saito M, Nishio Y, Kanno S, Uchiyama M, Hayashi A, Takagi M, Kikuchi H, Yamasaki H, Shimomura T, Iizuka O, Mori E. Cognitive Profile of Idiopathic Normal Pressure Hydrocephalus. Dement Geriatric Cogn Disorders Extra. 2011;1(1):202–11. https://doi.org/10.1159/000328924 . Savolainen S, Hurskainen H, Paljärvi L, Alafuzoff I, Vapalahti M. Five-Year Outcome of Normal Pressure Hydrocephalus with or Without a Shunt: Predictive Value of the Clinical Signs, Neuropsychological Evaluation and Infusion Test. Acta Neurochir. 2002;144(6):515–23. https://doi.org/10.1007/s00701-002-0936–3 . Shin C, Park MH, Lee S-H, Ko Y-H, Kim Y-K, Han K-M, Jeong H-G, Han C. Usefulness of the 15-item geriatric depression scale (GDS–15) for classifying minor and major depressive disorders among community-dwelling elders. J Affect Disord. 2019;259:370–5. https://doi.org/10.1016/j.jad.2019.08.053 . Shprecher D, Schwalb J, Kurlan R. Normal pressure hydrocephalus: Diagnosis and treatment. Curr Neurol Neurosci Rep. 2008;8(5):371–6. https://doi.org/10.1007/s11910-008-0058–2 . Skalický P, Mládek A, Vlasák A, Whitley H, Bradáč O. First experiences with Miethke M.blue® valve in iNPH patients. J Clin Neurosci. 2022;98:127–32. https://doi.org/10.1016/j.jocn.2022.02.004 . Solana E, Sahuquillo J, Junque C, Quintana M, Poca MA. Cognitive Disturbances and Neuropsychological Changes after Surgical Treatment in a Cohort of 185 Patients with Idiopathic Normal Pressure Hydrocephalus. Arch Clin Neuropsychol. 2012;27(3):304–17. https://doi.org/10.1093/arclin/acs002 . Štěpánková H, Bezdíček O, Nikolai T, Horáková K, Lukavský J, Kopeček M. Zpráva o projektu Národní normativní studie kognitivních determinant zdravého stárnutí. E-Psychologie. 2015;9(1):43–64. Thomas G, McGirt MJ, Woodworth G, Heidler J, Rigamonti D, Hillis AE, Williams MA. Baseline Neuropsychological Profile and Cognitive Response to Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus. Dement Geriatr Cogn Disord. 2005;20(2–3):163–8. https://doi.org/10.1159/000087092 . Xiao H, Hu F, Ding J, Ye Z. Cognitive Impairment in Idiopathic Normal Pressure Hydrocephalus. Neurosci Bull. 2022;38(9):1085–96. https://doi.org/10.1007/s12264-022-00873–2 . Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, Leirer VO. Development and validation of a geriatric depression screening scale: A preliminary report. J Psychiatr Res. 1982;17(1):37–49. https://doi.org/10.1016/0022–3956(82)90033–4 . Yeung PY, Wong LL, Chan CC, Yung CY, Leung LJ, Tam YY, Tang LN, Li HS, Lau ML. Montreal Cognitive Assessment—Single Cutoff Achieves Screening Purpose. Neuropsychiatr Dis Treat. 2020;16:2681–7. https://doi.org/10.2147/NDT.S269243 . Additional Declarations No competing interests reported. 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. 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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-6802703","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":466167085,"identity":"1d3e5263-9b05-4f47-9f09-5aeab54854ac","order_by":0,"name":"Ondřej Rýdlo","email":"","orcid":"","institution":"Charles University and Motol University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ondřej","middleName":"","lastName":"Rýdlo","suffix":""},{"id":466167086,"identity":"ef784854-ef72-488d-881a-95e5443df476","order_by":1,"name":"Adéla Bubeníková","email":"data:image/png;base64,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","orcid":"","institution":"Charles University and Motol University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Adéla","middleName":"","lastName":"Bubeníková","suffix":""},{"id":466167087,"identity":"6f202900-0746-457a-82af-b6c9c7609814","order_by":2,"name":"Petr Skalický","email":"","orcid":"","institution":"Charles University","correspondingAuthor":false,"prefix":"","firstName":"Petr","middleName":"","lastName":"Skalický","suffix":""},{"id":466167088,"identity":"b7fb5a08-737b-4cfa-b3bd-3335b0cae360","order_by":3,"name":"Klára Häcklová","email":"","orcid":"","institution":"Charles University and Military University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Klára","middleName":"","lastName":"Häcklová","suffix":""},{"id":466167089,"identity":"b3d8e5d0-7d38-44cc-96a3-1106777c7725","order_by":4,"name":"Robért Leško","email":"","orcid":"","institution":"Charles University and Motol University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Robért","middleName":"","lastName":"Leško","suffix":""},{"id":466167090,"identity":"24bdd95e-2e1d-418b-b993-dadcde966d1c","order_by":5,"name":"Aleš Vlasák","email":"","orcid":"","institution":"Charles University and Motol University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aleš","middleName":"","lastName":"Vlasák","suffix":""},{"id":466167091,"identity":"e4323d56-e6bd-4464-ab49-fff0ab4e17d1","order_by":6,"name":"Hana Georgi","email":"","orcid":"","institution":"Prague College of Psychosocial Studies","correspondingAuthor":false,"prefix":"","firstName":"Hana","middleName":"","lastName":"Georgi","suffix":""},{"id":466167092,"identity":"4d2cfe49-102f-4571-8c4b-19ab392a348b","order_by":7,"name":"Ondřej Bradáč","email":"","orcid":"","institution":"Charles University and Motol University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ondřej","middleName":"","lastName":"Bradáč","suffix":""}],"badges":[],"createdAt":"2025-06-02 13:38:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6802703/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6802703/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85319239,"identity":"62441900-93ac-42b4-b89f-c5a0dfd01618","added_by":"auto","created_at":"2025-06-24 15:01:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":894466,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6802703/v1/2a40d1f8-fff0-47de-bd4c-2a18668803d0.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Challenges in Neuropsychological Improvement After Shunt Surgery for Idiopathic Normal Pressure Hydrocephalus","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIdiopathic normal pressure hydrocephalus (iNPH) is a condition characterized typically by the Hakim's triad: incontinence, gait disturbance and cognitive decline (Nakajima et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). It predominantly affects the elderly, with a prevalence of 1.4\u0026ndash;3.7%, increasing with age (Andersson et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2019\u003c/span\u003e; Shprecher et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). The most prominent symptom is gait disturbance, occurring approximately in 90\u0026ndash;100% of patients, followed by the cognitive decline occurring in 78\u0026ndash;98% of patients (Agerskov et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Nakajima et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Cognitive decline in iNPH significantly impacts patients' quality of life and functional independence. Ventriculoperitoneal shunting (VPS) is the standard treatment aimed at restoring cerebrospinal fluid (CSF) dynamics, yet the extent and mechanisms of cognitive improvement remain under investigation.\u003c/p\u003e \u003cp\u003eCognitive assessment in iNPH often relies on global screening tools such as the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), both of which show postoperative improvement (H\u0026uuml;lser et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Xiao et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The overall cognitive improvement may correlate with the depth and nature of cognitive deficits before surgery (Thomas et al., \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). However, regardless of the severity of the cognitive deficit, the shorter the time since the onset of symptoms, the greater the expected postoperative improvement in cognitive performance (Xiao et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). While global cognitive screening is useful, it provides limited insight into the specific neuropsychological profile of iNPH patients. Tools like the MoCA rely on abbreviated versions of comprehensive tests, often missing subtle domain-specific deficits. As a result, screenings alone cannot capture which cognitive domains are most affected or how they change post-treatment. Incorporating detailed neuropsychological assessment can therefore enhance diagnosis, treatment planning, and monitoring of cognitive changes.\u003c/p\u003e \u003cp\u003eThe most affected cognitive domains in iNPH are executive functions (EFs), memory, and psychomotor pace (PP), with attention also showing significant impairment (R\u0026yacute;dlo et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Xiao et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). On the other hand, there is inconclusiveness regarding visuo-spatial abilities (Bugalho et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Xiao et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) and the language seems to be mostly spared (Saito et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2011\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eEF deficits are among the most studied and appear to improve after shunting, though findings remain inconsistent (Bugalho et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2014\u003c/span\u003e; Devito et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2005\u003c/span\u003e; Hellstr\u0026ouml;m et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Katzen et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; Laidet et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Solana et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). While some studies report significant gains, others only observe statistical trends (H\u0026uuml;lser et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Memory dysfunction, particularly in verbal and non-verbal long-term recall, also improves postoperatively, suggesting a role for CSF restoration in cognitive recovery (R\u0026yacute;dlo et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). There is a significant improvement after shunt surgery in long term memory, both verbal (Hellstr\u0026ouml;m et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Solana et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2012\u003c/span\u003e) and non-verbal (Skalick\u0026yacute; et al., \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Thomas et al., \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). Attention, closely linked to EFs, seems more impaired in iNPH compared to Alzheimer\u0026rsquo;s disease, and some studies suggest it improves after surgery, further supporting the need for targeted cognitive rehabilitation. (H\u0026uuml;lser et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; Ogino et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; R\u0026yacute;dlo et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite these findings, the literature on detailed cognitive profiling in iNPH remains limited. A more precise understanding of cognitive deficits before and after shunting is crucial for refining the diagnostic process, differentiating dementia subtypes, and optimizing patient management. Future research should prioritize comprehensive neuropsychological assessments to enhance treatment strategies and improve patient outcomes.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eBetween 2018 and 2021, a total of 126 patients with suspected iNPH were evaluated at the Department of Neurosurgery and Neuro-oncology. They underwent a comprehensive diagnostic protocol, including clinical, psychological, imaging, and functional assessments. To be included in the study, patients had to meet the following criteria: (1) symptom onset lasting at least three months, (2) an Evans\u0026rsquo; index greater than 0.3, (3) gait disturbance along with at least one additional symptom from Hakim\u0026rsquo;s triad, and (4) no other known condition that could explain their symptoms. Admitted patients underwent lumbar infusion test (LIT) and CSF drainage for 120 hours. After that, the clinical evaluation was repeated. All patients improving 15% on the Dutch Gait Scale and imaging criteria were evaluated as probable iNPH and consequently underwent shunt surgery. If the criteria were not met, the patients were referred for further outpatient surveillance.\u003c/p\u003e \u003cp\u003eOut of the 126 patients admitted for suspected iNPH, 56 patients fulfilled given diagnostic criteria and had been included in this study. Out of the 56 participants included in the study from neurosurgical perspective, we excluded all participants with GDS-15 score 10 or higher (n\u0026thinsp;=\u0026thinsp;3), which is an indication of severe depressive symptoms that can interfere with cognitive abilities (Shin et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Then, we excluded all participants with a MoCA score lower than 18 (n\u0026thinsp;=\u0026thinsp;20), which is an artificial but suggested border that is used for controlling the severity of cognitive decline (Milani et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Yeung et al., \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). In summary, the results of 33 experimental patients were analyzed. The neuropsychological assessment was conducted in a standard clinical setting by a trained neuropsychologist that did not know the results of the other functional testing. The testing took place before shunt implantation and 3 months after the surgery.\u003c/p\u003e \u003cp\u003eThe control group consisted of 71 healthy probands who were derived from the National Normative Study of Cognitive Determinants of Healthy Aging, NANOK (Štěp\u0026aacute;nkov\u0026aacute; et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). This sample was adjusted to the experimental group by age, education and gender.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eNeuropsychological Battery\u003c/h3\u003e\n\u003cp\u003eWe used a complex neuropsychological battery that was created by trained neuropsychologists with regard to the iNPH patient cognitive profile. The battery evaluated multiple cognitive domains. For EFs we used the Trail Making test in form B (Bezdicek et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2017\u003c/span\u003e), the Block Design subtest of Wechsler Adult Intelligence Scale (Černochov\u0026aacute; et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2010\u003c/span\u003e), the Rey-Osterrieth Complex Figure Test (Drozdov\u0026aacute; et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) and the Letter Fluency (czech standardized version with letters N, K, P, Nikolai et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). For vM we used the results of the Auditory Verbal Learning Test (AVLT; score for I-V trial, VI trial and 30 min delay recall, Frydrychov\u0026aacute; et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2018\u003c/span\u003e). Similarly, we used the ROCF reproduction (3 min) and 30 min delay recall for Non-verbal Memory. We furthermore assessed Psychomotor Pace with TMT version A (Bezdicek et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2017\u003c/span\u003e) and Language with Category fluency (czech standardized version for animals and vegetables, Nikolai et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Additionally, we used the Montreal Cognitive Assessment (Kopecek et al., \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2017\u003c/span\u003e; Nasreddine et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2005\u003c/span\u003e) as a global screening of cognitive performance, which includes subtests assessing the patient's visuoconstructional, executive functions, memory, attention, and verbal functions. Lastly, we assessed depressive symptoms with Geriatric Depression Scale (GDS-15) with fifteen items, a shortened version of the original 30-items questionnaire (Yesavage et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e1982\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eFor comparing the control group with the 3 months post-shunt NPH group, the appropriate statistical test was chosen based on the normality and homogeneity of variance assumptions. The normality of the data was analyzed with the Kolmogorov-Smirnov test. An Independent Samples t-Test was used for normally distributed data with equal variances. Within the NPH group, paired t-tests were used to compare pre-shunt and post-shunt (3 months) scores. The magnitude of change was evaluated according to Cohen\u0026rsquo;s criteria (0.5\u0026thinsp;=\u0026thinsp;large, 0.3\u0026thinsp;=\u0026thinsp;medium, 0.1\u0026thinsp;=\u0026thinsp;small). Statistical significance will generally be considered at a threshold of p\u0026thinsp;\u0026lt;\u0026thinsp;0.050. All statistical analyses were conducted with Jamovi statistical software (v2.3, The Jamovi Project 2022, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.jamovi.org/\u003c/span\u003e\u003cspan address=\"https://www.jamovi.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e).\u003c/span\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eCognitive Performance Before and After Shunt Surgery\u003c/h2\u003e \u003cp\u003eWe analyzed cognitive performance in iNPH patients pre- and three months post-shunt surgery. Paired-samples t-test showed no significant change in MoCA scores (21.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.35 vs. 21.35\u0026thinsp;\u0026plusmn;\u0026thinsp;4.36, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, vM improved significantly: AVLT I-V (24.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.68 vs. 29.11\u0026thinsp;\u0026plusmn;\u0026thinsp;8.72, p\u0026thinsp;=\u0026thinsp;0.033), AVLT VI (2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24 vs. 3.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18, p\u0026thinsp;=\u0026thinsp;0.043), and AVLT VII (2.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36 vs. 3.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.82, p\u0026thinsp;=\u0026thinsp;0.007). nvM did not significantly improve: ROCF 3M (9.36\u0026thinsp;\u0026plusmn;\u0026thinsp;6.11 vs. 11.26\u0026thinsp;\u0026plusmn;\u0026thinsp;5.72, p\u0026thinsp;=\u0026thinsp;0.100) and ROCF 30M (10.02\u0026thinsp;\u0026plusmn;\u0026thinsp;5.92 vs. 11.24\u0026thinsp;\u0026plusmn;\u0026thinsp;4.84, p\u0026thinsp;=\u0026thinsp;0.297).\u003c/p\u003e \u003cp\u003eEFs showed mixed results. While TMT B (200.48\u0026thinsp;\u0026plusmn;\u0026thinsp;74.17 vs. 197\u0026thinsp;\u0026plusmn;\u0026thinsp;112.72, p\u0026thinsp;=\u0026thinsp;0.890) and NKP (25.83\u0026thinsp;\u0026plusmn;\u0026thinsp;10.19 vs. 28.72\u0026thinsp;\u0026plusmn;\u0026thinsp;10.48, p\u0026thinsp;=\u0026thinsp;0.070) did not reach significance, the BDT improved significantly (20.82\u0026thinsp;\u0026plusmn;\u0026thinsp;7.82 vs. 25.04\u0026thinsp;\u0026plusmn;\u0026thinsp;8.34, p\u0026thinsp;=\u0026thinsp;0.002). PP significantly improved, with TMT A scores decreasing (86.55\u0026thinsp;\u0026plusmn;\u0026thinsp;34.09 vs. 75.01\u0026thinsp;\u0026plusmn;\u0026thinsp;29.96, p\u0026thinsp;=\u0026thinsp;0.030). VA and LA did not change significantly: ROCF-copy (27.09\u0026thinsp;\u0026plusmn;\u0026thinsp;7.54 vs. 27.95\u0026thinsp;\u0026plusmn;\u0026thinsp;6.26, p\u0026thinsp;=\u0026thinsp;0.483), Animals (14.79\u0026thinsp;\u0026plusmn;\u0026thinsp;5.49 vs. 14.90\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50, p\u0026thinsp;=\u0026thinsp;0.916), and Vegetables (8.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53 vs. 8.45\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34, p\u0026thinsp;=\u0026thinsp;0.498). Depressive symptoms, assessed via GDS-15, significantly decreased (4.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.76 vs. 3.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38, p\u0026thinsp;=\u0026thinsp;0.020).\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\u003eCognitive Performance of iNPH Patients Before and After Shunt Surgery.\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=\"char\" char=\"\u0026plusmn;\" 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=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePre-Intervention (M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePost-Intervention (M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003et-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eEffect Size (d)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlobal Cognition\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMoCA\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.33\u0026thinsp;\u0026plusmn;\u0026thinsp;2.35\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21.35\u0026thinsp;\u0026plusmn;\u0026thinsp;4.36\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.02\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVerbal Memory (vM)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAVLT I-V\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.7\u0026thinsp;\u0026plusmn;\u0026thinsp;8.68\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.11\u0026thinsp;\u0026plusmn;\u0026thinsp;8.72\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-2.26\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e.033\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.434\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAVLT VI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e3.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-2.12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.043\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e-0.393\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAVLT VII\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e2.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.36\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e3.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.82\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-2.93\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.007\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e-0.544\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNon-Verbal Memory (nvM)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eROCF 3M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e9.36\u0026thinsp;\u0026plusmn;\u0026thinsp;6.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e11.26\u0026thinsp;\u0026plusmn;\u0026thinsp;5.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-1.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.316\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eROCF 30M\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.02\u0026thinsp;\u0026plusmn;\u0026thinsp;5.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e11.24\u0026thinsp;\u0026plusmn;\u0026thinsp;4.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.297\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.213\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExecutive Functions (EFs)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMT B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e200.48\u0026thinsp;\u0026plusmn;\u0026thinsp;74.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e197\u0026thinsp;\u0026plusmn;\u0026thinsp;112.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.890\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNKP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e25.83\u0026thinsp;\u0026plusmn;\u0026thinsp;10.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e28.72\u0026thinsp;\u0026plusmn;\u0026thinsp;10.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.349\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eBDT\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e20.82\u0026thinsp;\u0026plusmn;\u0026thinsp;7.82\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e25.04\u0026thinsp;\u0026plusmn;\u0026thinsp;8.34\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-3.51\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e-0.663\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePsychomotor Pace (PP)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTMT A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e86.55\u0026thinsp;\u0026plusmn;\u0026thinsp;34.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e75.01\u0026thinsp;\u0026plusmn;\u0026thinsp;29.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.425\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVisuospatial Abilities (VA)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eROCF-copy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e27.09\u0026thinsp;\u0026plusmn;\u0026thinsp;7.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e27.95\u0026thinsp;\u0026plusmn;\u0026thinsp;6.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.483\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLanguage (LA)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAnimals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e14.79\u0026thinsp;\u0026plusmn;\u0026thinsp;5.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e14.90\u0026thinsp;\u0026plusmn;\u0026thinsp;4.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.916\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVegetables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.45\u0026thinsp;\u0026plusmn;\u0026thinsp;2.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e-0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.498\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e-0.127\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDepressive Symptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eGDS-15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e4.72\u0026thinsp;\u0026plusmn;\u0026thinsp;2.76\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e3.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e2.47\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.020\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.458\u003c/b\u003e\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\u003eMoCA - Montreal Cognitive Assessment, AVLT - Auditory Verbal Learning Test, ROCF - Rey-Osterrieth Complex Figure, TMT - Trail Making Test, GDS-15 - Geriatric Depression Scale 15 items\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eComparison Between iNPH Patients and Healthy Controls\u003c/h2\u003e \u003cp\u003eTo assess post-surgery cognitive outcomes, we compared iNPH patients (71.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2 years, 69.7% male) with healthy controls (72.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 years, 62% male, Table XX). The groups did not significantly differ in demographics. Independent t-tests showed significant cognitive differences favoring the control group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). MoCA, AVLT I-V, AVLT VI, AVLT VII, ROCF 3M, ROCF 30M, TMT B, NKP, Animals, TMT A (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), ROCF Copy (p\u0026thinsp;=\u0026thinsp;0.006), and GDS-15 (p\u0026thinsp;=\u0026thinsp;0.004) all showed significant differences, with iNPH patients performing worse.\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\u003eDescriptives\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAge (M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eiNPH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e71.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69.7%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e72.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62%\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\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison Between iNPH Patients and Healthy Controls.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\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=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003et-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEffect Size (d)\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\u003eMoCA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAVLT I-V\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAVLT VI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e8.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAVLT VII\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF 3M\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.93\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF 30M\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT B\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-4.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNKP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.216\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAnimals\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.371\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTMT A\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-4.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eROCF Copy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.615\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGDS-15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-2.93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.645\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\u003eMoCA - Montreal Cognitive Assessment, AVLT - Auditory Verbal Learning Test, ROCF - Rey-Osterrieth Complex Figure, TMT - Trail Making Test, NKP - Letter fluency test, GDS-15 - Geriatric Depression Scale 15 items\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe examined a detailed neuropsychological profile of patients with iNPH and its development after shunt surgery. We applied a complex neuropsychological battery before shunt surgery and three months after shunt surgery to see mid-term effects of the treatment. We used a control group of healthy individuals to assess the cognitive performance of iNPH patients 3 months after shunt surgery in order to assess magnitude of change and determine normality of cognitive performance. Utilizing a multidimensional neuropsychological battery administered both prior to and three months following shunting, and contrasting patient performance against a matched healthy control group, we aimed to delineate the trajectory of cognitive changes and their clinical significance. The most compelling and consistent finding was the significant postoperative improvement in vM, which, although still below normative levels, demonstrated the greatest relative gain among all evaluated cognitive domains. This result underscores the centrality of vM as a surgery-sensitive domain in iNPH and supports the notion that specific aspects of memory\u0026mdash;especially those dependent on fronto-subcortical connectivity\u0026mdash;are amenable to intervention via CSF diversion. (Xiao et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). Our recent study suggests that the memory impairment might be uneven in its verbal and non-verbal parts (R\u0026yacute;dlo et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). nvM, in contrast to vM, remained significantly impaired three months postoperatively and did not exhibit measurable improvement. This persistence of dysfunction despite relatively milder baseline impairment raises several interpretations: it is possible that nvM, due to either different neural circuitry or structural damage, possesses a higher threshold for recovery or exhibits a more protracted response to CSF modulation. Alternatively, nvM-related deficits may reflect more permanent neuropathological alterations. While some longitudinal studies report delayed cognitive improvement\u0026mdash;most notably at the 12-month mark\u0026mdash; (B\u0026uuml;y\u0026uuml;kg\u0026ouml;k et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) others suggest a transient or even absent effect of shunting on cognition, highlighting the variability of neuropsychological outcomes in this population (Lilja-Lund et al., \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eImportantly, the distinctive effect on vM and nvM may serve as a useful tool in clinical differentiation, particularly in distinguishing iNPH from Alzheimer\u0026rsquo;s disease (AD), where both memory systems are often compromised due to hippocampal atrophy. (Picascia, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In our study, the relative preservation of nvM in iNPH patients could constitute a potential diagnostic indicator, bolstering the clinical utility of memory subdomain profiling in the context of neurodegenerative differential diagnosis. This aligns with earlier literature suggesting that AD is typified by a more global mnemonic disruption, and reinforces the need for targeted neuropsychological batteries in clinical assessments.\u003c/p\u003e \u003cp\u003eThe domain of EFs yielded mixed results. Contrary to expectations and previous findings, our cohort did not demonstrate improvement in set-shifting ability, as assessed via the TMT-B. This result may suggest that certain executive functions are less responsive to the effects of shunting, or that inter-individual variability masks group-level changes (Duinkerke et al., \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2004\u003c/span\u003e; Mataro et al., \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2006\u003c/span\u003e; Thomas et al., \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2005\u003c/span\u003e). The absence of improvement in TMT-B could also reflect limitations in sensitivity of this task or high baseline variability in performance. Similarly, verbal fluency\u0026mdash;a task also associated with shifting and executive control\u0026mdash;exhibited a positive trend that failed to reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.070). In contrast, performance on the BDT, a task reflecting visuo-constructive planning and execution, improved markedly, with the largest effect size observed across all assessments (d = -0.660). This finding suggests that executive domains reliant on structured planning rather than rapid cognitive flexibility may be more susceptible to recovery following CSF diversion. Given that BDT engages strategic organization, working memory, and spatial planning\u0026mdash;processes mediated by dorsolateral prefrontal and parietal regions\u0026mdash;these results may point to a more selective restoration of frontoparietal networks post-surgery (Ogino et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2006\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePsychomotor processing speed, assessed via TMT-A, significantly improved after shunt surgery, a finding in close alignment with the broader literature that characterizes psychomotor slowing as a core cognitive feature of iNPH (Xiao et al., \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). The improvement in this domain strengthens the hypothesis that psychomotor speed serves as a sensitive index of functional change and therapeutic responsiveness. Although some earlier reports, such as those by Savolainen et al. (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2002\u003c/span\u003e) noted no significant change in TMT-A scores, these inconsistencies may arise from methodological differences, variable follow-up durations, or heterogeneous patient cohorts. It is also noteworthy that subjective clinical improvement may not always be captured by psychometric indices, underscoring the importance of triangulating data sources in the assessment of surgical efficacy.\u003c/p\u003e \u003cp\u003eIn the domains of VA and LA, no significant postoperative changes were observed. Importantly, the VA domain appeared to be among the least impaired both pre- and postoperatively relative to healthy controls. This may reflect a floor effect in recovery: domains that are relatively intact at baseline may lack the functional deficit necessary to elicit measurable improvement. Alternatively, these findings may point to the limited sensitivity of the employed neuropsychological instruments in detecting subtle or subclinical changes in these functions. It remains to be investigated whether more fine-grained or dynamic assessments might capture such changes more accurately. On the other hand, the cognitive capabilities of patients are typically limited and neuropsychological protocol should strive for maximum sensitivity and should minimize overload of patients.\u003c/p\u003e \u003cp\u003eOur research and above mentioned scope of literature supports overall positive neuropsychological outcomes of shunt surgery. Nevertheless, to some degree the positive outcome is controversial and appears to vary among individuals and also vary in time after the surgery. In fact, Solana et al. (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2012\u003c/span\u003e) found that when assessed as a group, the positive effect in neuropsychological outcomes is visible, however, when assessed individually less than 50% of the patients can be classified as improved. This poses a significant challenge for the future. We now accept the overall benefit of shunt surgery on cognitive performance for iNPH patients, however we know little about individual specific factors that could predict or contradict the response in this clinical feature and it is of high importance to develop sufficient diagnostic processes not only for the diagnosis itself but also for the management of the patient\u0026rsquo;s care and patient\u0026rsquo;s expectations.\u003c/p\u003e \u003cp\u003eBeyond cognitive outcomes, our study identified a noteworthy alleviation of depressive symptoms following shunt surgery. Although depressive symptoms remained elevated in comparison to healthy adults, the reduction from preoperative levels was statistically and clinically significant. This contrasts with previous findings, such as those by Israelsson et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2016\u003c/span\u003e) who reported sustained depressive symptomatology postoperatively but did not assess pre-shunt affective status. Our data suggest that, at least in the early postoperative phase, CSF diversion may confer a beneficial effect on mood. Given the bidirectional relationship between mood and cognition, the improvement in depressive symptoms may not only reflect direct affective benefit but may also secondarily enhance cognitive performance, motivation, and quality of life. The persistence of subclinical depression, however, warrants ongoing monitoring and further investigation into its neurobiological underpinnings and long-term evolution.\u003c/p\u003e \u003cp\u003eAnother critical methodological observation arising from our study is the inadequacy of global cognitive screening tools\u0026mdash;specifically the MoCA\u0026mdash;in detecting postoperative cognitive changes. Despite the documented improvements revealed by the comprehensive neuropsychological battery, MoCA scores did not reflect these gains. This highlights a major limitation in using brief cognitive screening instruments in the postoperative evaluation of iNPH patients and argues strongly for the adoption of domain-specific assessments as standard practice in both clinical and research settings.\u003c/p\u003e\n\u003ch3\u003eStudy Strengths and Limitations\u003c/h3\u003e\n\u003cp\u003eSeveral limitations of the present study merit discussion. The diagnostic accuracy of preoperative CSF testing (e.g., lumbar infusion and drainage procedures) remains imperfect, potentially resulting in the exclusion of patients who might have benefitted from shunting. Although response to shunting is the gold standard for definitive diagnosis, this dependency introduces a degree of selection bias inherent to all iNPH studies. Furthermore, the three-month follow-up period, while clinically standard, limits conclusions regarding the durability and temporal progression of cognitive changes. Longer-term assessments are necessary to capture delayed or regressive cognitive trajectories. The neuropsychological battery, although comprehensive and tailored to patient tolerability, did not cover all cognitive domains in equal depth, and several domains were represented by only one test, which constrains interpretative robustness. The use of raw scores, while preserving ecological validity, may limit cross-study comparability, though it mitigates transformation-induced distortion. The sample size, while adequate for group-level inference, restricts generalizability and precludes finer-grained subgroup analyses. We did not stratify patients based on cognitive reserve, functional capacity, or symptom duration, all of which may modulate responsiveness to surgical intervention and should be considered in future studies. Additionally, estimating symptom onset retrospectively via caregiver reports introduces a further layer of uncertainty (Krahulik et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eNevertheless, the inclusion of age-, sex-, and education-matched healthy controls strengthens the interpretive validity of our findings, particularly in assessing the normalization\u0026mdash;or lack thereof\u0026mdash;of postoperative cognitive performance. While this design provides a valuable point of reference, our findings must ultimately be contextualized within the broader heterogeneity of iNPH populations. Indeed, as highlighted by Solana et al. (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2012\u003c/span\u003e), group-level improvements may obscure considerable intra-individual variability, with fewer than half of patients showing significant cognitive gains when assessed individually. This presents a formidable clinical challenge: while the general benefit of shunt surgery is increasingly recognized, little is known about the predictors of individual cognitive outcomes. There remains an urgent need to develop prognostic models incorporating neuropsychological, neuroimaging, and biomarker data to improve patient selection, inform surgical decision-making, and manage postoperative expectations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe shunt surgery seems to positively influence the neuropsychological performance of patients with iNPH. The most compelling and consistent finding was the significant postoperative improvement in vM, which, although still below normative levels, demonstrated the greatest relative gain among all evaluated cognitive domains. This result underscores the centrality of vM as a surgery-sensitive domain in iNPH and supports the notion that specific aspects of memory\u0026mdash;especially those dependent on fronto-subcortical connectivity\u0026mdash;are amenable to intervention via CSF diversion. Along with vM, PP also significantly improved, which strengthens the hypothesis that psychomotor speed serves as a sensitive index of functional change and therapeutic responsiveness. Interestingly, mixed results were found for EFs, that contrary to prior findings did not demonstrate improvement in set-shifting ability but improved part of the EFs reliant on structured planning rather than rapid cognitive flexibility. Visuospatial abilities and language remained unimproved by the shunt surgery. It is also noteworthy that none of the cognitive domains declined during the study period, and the absence of deterioration can be interpreted as a positive outcome in itself. Beyond cognitive outcomes, our study identified an alleviation of depressive symptoms following shunt surgery. Although depressive symptoms remained elevated in comparison to healthy adults, the reduction from preoperative levels was statistically and clinically significant.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethics board of the Military University Hospital Prague. Informed consent was obtained from all patients before their inclusion into the database and following procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Ministry of Health of the Czech Republic number NU23-04-00551.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ondřej Rýdlo, Adéla Bubeníková, Petr Skalický, and Ondřej Bradáč. The first draft of the manuscript was written by Ondřej Rýdlo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAgerskov S, Hellstr\u0026ouml;m P, Andr\u0026eacute;n K, Koll\u0026eacute;n L, Wikkels\u0026ouml; C, Tullberg M. The phenotype of idiopathic normal pressure hydrocephalus-a single center study of 429 patients. 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J Psychiatr Res. 1982;17(1):37\u0026ndash;49. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0022\u0026ndash;3956(82)90033\u0026ndash;4\u003c/span\u003e\u003cspan address=\"10.1016/0022\u0026ndash;3956(82)90033\u0026ndash;4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYeung PY, Wong LL, Chan CC, Yung CY, Leung LJ, Tam YY, Tang LN, Li HS, Lau ML. Montreal Cognitive Assessment\u0026mdash;Single Cutoff Achieves Screening Purpose. Neuropsychiatr Dis Treat. 2020;16:2681\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/NDT.S269243\u003c/span\u003e\u003cspan address=\"10.2147/NDT.S269243\" 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":"normal pressure hydrocephalus, neuropsychology, cognitive decline, cognitive domain, depression","lastPublishedDoi":"10.21203/rs.3.rs-6802703/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6802703/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eWe sought to analyze cognitive performance and depressive symptoms of Idiopathic Normal Pressure Hydrocephalus (iNPH) patients three months after the shunt surgery. We assembled different neuropsychological tests into specific cognitive domains: Verbal Memory, Non-Verbal Memory, Executive Functions, Visuo-spatial Abilities, Language and Psychomotor Pace.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eINPH patients underwent a complex neuropsychological assessment prior to the shunt surgery and three months after. We compared the results of cognitive performance before and after the shunt surgery in order to assess the effect of the surgery on cognition and depressive symptoms. Additionally, we compared the post-surgical cognitive performance of iNPH patients to age, sex- and education-matched group of healthy controls to see whether the iNPH patients reached the performance level of the normal population.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOut of the 126 patients for suspected iNPH 33 patients met all the inclusion criteria. Additionally, we used 71 healthy controls. For the analysis of cognitive performance change after shunt surgery we found significant improvement in tests covering Verbal Memory (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.033, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.043 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007) and Psychomotor Pace (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). We found mixed results for tests covering Executive functions (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.890, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.070, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002). We found no improvement for the tests covering Non-Verbal Memory (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.100, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.297), Language (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.916, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.498) and Visuo-spatial Abilities (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.483). We also found improvement in depressive symptoms (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.020). For the analysis of the 3 months after surgery iNPH patients cognitive performance and control group cognitive performance we found all neuropsychological tests to significantly differ (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eShunt surgery appears to have a positive effect on the neuropsychological performance of patients with iNPH. However, the improvement is limited. First, the effect does not appear to be comprehensive but rather restricted to certain neuropsychological domains. We observed improvements in the Verbal Memory and Psychomotor Pace domains, while results for Executive Functions were mixed\u0026mdash;suggesting a positive effect on patients' ability to plan but no effect on their ability to shift. No effects were found for Visuospatial Abilities or Language. Second, the improvement appears to be limited in magnitude. Although overall performance improves three months after surgery, it still does not reach the level of healthy individuals. Nevertheless, the absence of worsening might also be seen as a positive effect. Interestingly, depressive symptoms followed a similar pattern to cognitive functioning before and after surgery. We found that shunt surgery significantly alleviated depressive symptoms.\u003c/p\u003e","manuscriptTitle":"Challenges in Neuropsychological Improvement After Shunt Surgery for Idiopathic Normal Pressure Hydrocephalus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-06 17:44:31","doi":"10.21203/rs.3.rs-6802703/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":"38abb957-2f72-4c0e-aed5-01f4f27965a0","owner":[],"postedDate":"June 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-24T14:53:36+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-06 17:44:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6802703","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6802703","identity":"rs-6802703","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}