Correlation between mesial temporal atrophy visual scale, hippocampal volumetry, and inferior lateral ventricle-hippocampus ratio in patients with Alzheimer’s dementia

Correlation between mesial temporal atrophy visual scale, hippocampal volumetry, and inferior lateral ventricle-hippocampus ratio in patients with Alzheimer’s dementia | 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 Correlation between mesial temporal atrophy visual scale, hippocampal volumetry, and inferior lateral ventricle-hippocampus ratio in patients with Alzheimer’s dementia debora semeia takaliuang, Rusli Muljadi, Ratna Sutanto, Rocksy Situmeang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7953365/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 Background: Alzheimer’s dementia is characterized by hippocampal atrophy and enlargement of the lateral ventricles, particularly the inferior portion. The visual assessment of medial temporal atrophy using the Mesial Temporal Atrophy (MTA) scale is commonly employed due to its simplicity; however, it remains subjective. Quantitative measurements of hippocampal volume and the inferior lateral ventricle–hippocampus ratio offer a more objective quantitative approach. Objective: To evaluate the correlation between the MTA visual scale, hippocampal volumetry, and the inferior lateral ventricle–hippocampus ratio in patients with Alzheimer’s dementia. Methods An ambispective study was conducted from January 2022 to July 2025. Subjects were patients with Alzheimer’s dementia who underwent brain MRI with T1-3D TFE sequences. The MTA visual scale was assessed independently by three readers. Hippocampal and inferior lateral ventricle volumetric analyses were performed using VolBrain software. Inter-reader reliability was assessed using Cohen’s κ, while correlations between variables were analyzed using Spearman’s test. Results A total of 36 subjects met the inclusion criteria. Inter-reader agreement was almost perfect (Cohen’s κ = 0.851–0.889). A moderate negative correlation was found between the MTA visual scale and hippocampal volumetry (r = − 0.341; p = 0.042), a very strong positive correlation between the MTA visual scale and the inferior lateral ventricle–hippocampus ratio (r = 0.843; p < 0.001), and a moderate negative correlation between hippocampal volumetry and the inferior lateral ventricle–hippocampus ratio (r = − 0.483; p = 0.003). Multivariate analysis showed that hippocampal and inferior lateral ventricle measurements were significant predictors of MTA score, contributing to 61.6% of its variance (R² = 0.616). Conclusion There is a significant correlation between the MTA visual scale, hippocampal volumetry, and the inferior lateral ventricle–hippocampus ratio. The inferior lateral ventricle–hippocampus ratio demonstrated the strongest correlation with the MTA score and may serve as a simple quantitative biomarker for assessing medial temporal atrophy in Alzheimer’s dementia. mesial temporal atrophy hippocampal volumetry inferior lateral ventricle inferior lateral ventricle–hippocampus ratio Figures Figure 1 Figure 2 Introduction Dementia is a multifactorial neurodegenerative disorder affecting approximately 47 million people worldwide, projected to reach 131 million by 2050. In the United States, its prevalence is estimated at 10% among individuals aged > 65 years, with Alzheimer’s disease being the most common cause in this group 1 – 4 . Progressive neuronal loss in AD results from the accumulation of abnormal proteins and neurodegenerative pathology. Given the limited regenerative capacity of aging neurons, early detection is crucial for improving clinical outcomes. 1 – 4 Hippocampal volume is a major imaging biomarker in AD, yet its quantitative measurement is time-consuming and may be influenced by cranial size. Scheltens et al. (1992) introduced the Medial Temporal Atrophy (MTA) visual scale as a semi-quantitative method for visually grading hippocampal atrophy, with sensitivity and specificity of 75% and 85%, respectively, for differentiating AD from healthy controls. 5 In addition to hippocampal atrophy, the ratio between hippocampal and inferior lateral ventricle (ILV) volumes has emerged as an important marker in AD, distinguishing true hippocampal atrophy from congenital variants. 6 However, early AD presents subtle changes, and visual detection of hippocampal atrophy can be challenging due to its small structure. Harper et al. (2015) reported satisfactory inter-reader reliability for MTA scoring (ICC = 0.8) and global cortical atrophy (ICC = 0.6) 7,8 Quantitative medial temporal lobe atrophy (QMTA) measurements based on hippocampal and ILV volumes have demonstrated good diagnostic accuracy. A meta-analysis by Park et al. (2022) reported pooled sensitivity and specificity of 82% and 87% for hippocampal volumetry in differentiating AD from healthy controls. 8 , 9 This study aimed to assess the correlation between MTA visual scale, hippocampal volume, and ILV/HPC ratio in Alzheimer’s disease patients. Establishing this relationship may facilitate more practical and reproducible MRI-based evaluation tools for clinicians and radiologists, supporting early diagnosis and longitudinal monitoring of neurodegenerative disorders. Subjects and Methods Study Design This ambispective study combined retrospective and prospective data of Alzheimer’s disease patients who underwent conventional brain MRI with a 3D T1-weighted Turbo Field Echo (TFE) sequence between January 2022 and July 2025. The study was approved by the Ethics Committee of the Faculty of Medicine, Universitas Pelita Harapan (Approval No. 219/K-LKJ/ETIK/VI/2025). MTA Visual Scale Assessment The MTA visual score was assessed on coronal T1-3D TFE images aligned parallel to the brainstem at the level of the anterior pons. Two radiologists and one senior radiology resident independently rated each case. In case of discrepancy, the senior radiologist determined the final score. Volumetric Measurement Hippocampal and inferior lateral ventricle volumetric data were obtained from T1-3D TFE images processed using VolBrain software. Absolute volumes were segmented automatically and normalized to intracranial volume (ICV), yielding relative hippocampal and ILV fractions (% of ICV). The ILV/HPC ratio was calculated as: Statistical Analysis Statistical analyses were performed using SPSS 26.0. Inter-reader reliability was evaluated with Cohen’s κ. Correlations between variables were analyzed using Spearman’s ρ. Variables with p ≤ 0.25 in bivariate analysis were included in multivariate linear regression models. A p-value < 0.05 was considered statistically significant. Results Study Population A total of 36 patients met the inclusion criteria (19 females [52.8%], 17 males [47.2%]). The majority were aged 75–84 years (41.7%), consistent with the typical demographic profile of Alzheimer’s disease (Table 1 ). Table 1 Sample characteristic Characteristic Mean ± SD (Min–Max) n (%) Age (years) — — 85 years — 1 (2.8%) MTA Visual Score 1.91 ± 0.2 (0–4) — ILV Volume 2.71 ± 0.24 (0.68–6.67) — Hippocampal Volume 5.87 ± 0.17 (0.35–7.83) — ILV/HPC Ratio 0.47 ± 0.49 (0.11–1.43) — Inter-reader reliability Cohen’s κ values indicated almost perfect agreement between all rater pairs: Reader 1 vs 2 = 0.852, Reader 2 vs 3 = 0.889, and Reader 1 vs 3 = 0.851 (p < 0.001 for all), according to Landis and Koch (1977). Corellation analyses • MTA vs Hippocampal Volume: Moderate negative correlation (r = − 0.341; p = 0.042). Increasing MTA score was associated with decreasing hippocampal volume (Fig. 1 ). • MTA vs ILV/HPC Ratio: Very strong positive correlation (r = 0.843; p < 0.001), indicating that higher MTA scores correspond to greater relative enlargement of the ILV compared to hippocampal volume (Fig. 2 ). Multivariate analysis Multiple linear regression identified hippocampal volume (B = − 0.289; p = 0.032) and ILV volume (B = 0.586; p < 0.001) as independent predictors of MTA visual score. The model explained 61.6% of the variance (R² = 0.616). MTA Score = 2.026 − 0.289(Hippocampal Volume) + 0.586(ILV Volume) Discussion Demographic and biological characteristics This study included 36 participants, consisting of 19 females (52.78%) and 17 males (47.22%). Although the difference was relatively small, females slightly predominated. This finding aligns with prior studies by Oveisgharan et al. (2018) 10 , Boccalini et al. (2025) 11 , and Buckley et al. (2019) 12 , supporting neuropathological evidence that women tend to exhibit a higher burden of neurofibrillary tau tangles (NFTs) and faster tau accumulation compared with men, both in presymptomatic and symptomatic stages of Alzheimer’s dementia. 13 Pathophysiologically, several mechanisms may underlie this observation. First, hormonal factors, particularly the postmenopausal decline in estrogen, eliminate neuroprotective effects such as regulation of cerebral glucose metabolism, inhibition of tau phosphorylation, and modulation of neuroinflammation. This promotes tau hyperphosphorylation and accelerates NFT formation. Second, genetic factors contribute significantly, female carriers of the APOE ε4 allele demonstrate greater tau accumulation and faster progression than male carriers. Third, postmortem neuropathological studies have shown higher NFT density in females even when amyloid load or overall atrophy levels are comparable to males. These findings collectively support the hypothesis that biological differences—including hormonal, genetic, and metabolic factors—underlie women’s increased vulnerability to Alzheimer’s dementia in both preclinical and clinical phases. 10−3 The prevalence of Alzheimer’s dementia increases sharply with age. In this study, the largest age group was 75–84 years (41.67%), consistent with European meta-analyses showing a steep risk escalation in this range, where incidence rises from 3.4 per 1,000 person-years at ages 65–74 to 13.8 at 75–84 years and 35.8 among individuals ≥ 85 years. 14 , 15 Only one participant (2.78%) in this study was older than 85 years, while the 75–84 year group dominated the sample (41.67%). This underrepresentation of the oldest-old population is consistent with global Alzheimer’s research trends, where individuals ≥ 85 years comprise only about 8% of clinical trial participants despite representing the majority of affected patients. 14 , 15 Several factors may explain the low representation of subjects > 85 years, including strict exclusion criteria to maintain sample homogeneity and the reluctance of elderly participants or their families due to physical burden and health risks, as also reported by Newmark et al. (2020) 16 Inter-Rater Reliability Inter-rater reliability analysis in this study showed Cohen’s κ values ranging from 0.85 to 0.88, indicating almost perfect agreement between raters. This exceeds the κ range reported by Cavallin et al. (2012) [32] (κ = 0.29–0.48) and by Rhodius et al. (2017) 17 (κ ≈ 0.80). These findings are comparable to the cohort study by Molinder et al. (2021) 18 , which reported κ = 0.83–0.87. Despite one reader being a senior radiology resident and the others experienced radiologists from different departments, inter-rater consistency remained high. This emphasizes that the standardized MTA visual rating method can minimize variability across different levels of expertise, consistent with Hakansson et al. (2021) 19 Although high κ values indicate strong reliability, interpretation must remain cautious. As McHugh (2012) 20 [63] noted, even κ values of 0.80–0.90, classified as “almost perfect,” represent actual agreement in only 64–81% of cases—meaning up to 36% of assessments may still differ. Therefore, while κ ≥ 0.80 is acceptable in clinical research, it should not be viewed as absolute proof of validity. Visual rating, though practical, remains subjective. Quantitative approaches (such as hippocampal volumetry or automated segmentation tools) show strong correlation with visual scores but cannot fully replace categorical agreement analysis; both should be applied complementarily 16 , 17 , 19 Correlation Between MTA Visual Scale and Hippocampal Volumetry Magnetic field strength differences between 1.5 T and 3 T MRI scanners may introduce bias in volumetric or visual MTA analyses. The 3 T MRI provides a higher signal-to-noise ratio and better anatomical delineation than 1.5 T, making automatic segmentation and visual scoring potentially more sensitive. 21 To minimize discrepancies, this study employed a standardized T1-3D Turbo Field Echo (TFE) isotropic acquisition protocol across both scanners. Furthermore, VolBrain software integrated the international Neuroimaging Consortium for the Evaluation of Alzheimer’s (NICE) protocol and adhered to the EADC–ADNI Harmonized Protocol (HarP) for hippocampal segmentation, improving inter-scanner consistency [51, 65, 66]. VolBrain also provides high reproducibility with shorter processing time, making it a reliable primary quantification tool. 22 A statistically significant moderate negative correlation was found between visual MTA scores and hippocampal volume (r = − 0.341; p = 0.042), indicating that higher MTA scores correspond to smaller hippocampal volumes. This finding aligns with Wittens et al. (2024) 7 .The MTA visual scale reflects not only hippocampal shrinkage but also the expansion of adjacent cerebrospinal fluid spaces (choroid fissure, hippocampal fissure, and inferior lateral ventricle), which may enlarge due to global atrophy. 7 Dhikav et al. (2017) 23 and Cavedo et al. (2014) 24 also reported significant correlations in Alzheimer’s dementia but not in healthy controls. Stronger correlations tend to appear in advanced disease stages, whereas early-stage patients show weaker associations. This suggests that the MTA scale is more sensitive for detecting structural changes in moderate to advanced Alzheimer’s disease. Nevertheless, the moderate correlation observed in this study implies that MTA scores and hippocampal volume are not fully interchangeable. MTA grading reflects broader medial temporal changes beyond hippocampal size, and factors such as individual anatomy, disease stage, and tissue hydration may influence correlation strength. 25 Despite these limitations, the clinical validity of the MTA visual scale remains well-supported by post-mortem confirmation studies 8 , 25 , 26 , reaffirming its utility as a rapid clinical screening tool, though not a substitute for quantitative hippocampal volumetry. Correlation Between MTA Visual Scale and Inferior Lateral Ventricle–Hippocampus Ratio A very strong positive correlation was observed between MTA visual scores and the inferior lateral ventricle–hippocampus (ILV/HPC) ratio (r = 0.843; p < 0.001), indicating that more severe medial temporal atrophy (higher MTA score) corresponds to greater relative ILV enlargement compared with hippocampal volume. This finding is consistent with Wittens et al. (2024) 7 , who demonstrated that the ILV/HPC ratio can serve as a quantitative parameter complementary to MTA visual grading, providing a simple alternative for clinical assessment of medial temporal atrophy. Nestor et al. (2008) 27 also reported that lateral ventricular enlargement, particularly in the inferior horn, strongly correlates with hippocampal atrophy and Alzheimer’s progression. Similarly, Rusinek et al. (2019) 28 found that the ILV/HPC ratio is an effective atrophy indicator, with sensitivity and specificity of 74%. Recent studies by Witten et al. (2024) 7 , Lozano et al. (2023) 29 , and Shen et al. (2023) 30 further suggest that the ILV/HPC ratio may outperform absolute hippocampal volume alone, as it accounts for relative structural balance between the hippocampus and surrounding ventricles, making it more dynamic and sensitive to progressive changes. To the best of our knowledge, previous studies have predominantly focused on the relationship between the MTA scale and absolute hippocampal volume, whereas the ILV/HPC ratio as an alternative indicator has been rarely explored. In Indonesia, local studies have so far evaluated hippocampal volumetry and ventricular enlargement separately without integrating both parameters into a unified ratio. Therefore, this study provides an important contribution to the regional literature by highlighting the ILV/HPC ratio as a potential quantitative biomarker for assessing medial temporal atrophy in Alzheimer’s dementia. Multivariate Analysis and Clinical Implications Multivariate regression analysis identified hippocampal and inferior lateral ventricle volumes as independent predictors of MTA visual scores, explaining approximately 62% of score variance. These findings confirm that MTA grading predominantly reflects true structural atrophy rather than age-related volume loss. Age and the ILV/HPC ratio did not contribute significantly once absolute volumetric variables were included, indicating their interdependence. The inverse relationship between hippocampal volume and MTA score reinforces the neuropathologic continuum of AD, while the direct association between ILV size and MTA underscores ex vacuo dilatation secondary to parenchymal loss. Clinically, these results validate the combined use of visual and quantitative assessments: visual MTA scoring for rapid screening and volumetric analysis for objective follow-up or research endpoints. Technical Considerations MRI field strength (1.5 T vs 3 T) can introduce bias in volumetric estimation due to differing signal-to-noise ratios and spatial resolution. This study minimized variability using standardized T1-3D TFE isotropic sequences and VolBrain’s harmonized processing pipeline (EADC-ADNI HarP protocol [51,65,66]), ensuring inter-scanner consistency. Limitations This single-center ambispective study had a modest sample size, with unequal distribution between 1.5 T (n = 13) and 3 T (n = 23) MRI data, potentially introducing bias. Although harmonized acquisition and volumetric normalization (ICV) were applied, future studies should employ uniform scanner strength and larger, multi-center cohorts to improve generalizability. Conclusion The MTA visual scale shows a moderate negative correlation with hippocampal volume (r = − 0.341; p = 0.042). A very strong positive correlation exists between the MTA visual scale and the ILV/HPC ratio (r = 0.843; p < 0.001). Both hippocampal and ILV volumes are independent predictors of MTA score, together explaining 61.6% of its variance. The ILV/HPC ratio offers a quantitative complement to the MTA visual scale, providing a rapid and reliable MRI biomarker for assessing medial temporal atrophy in Alzheimer’s disease. Declarations Author Contribution Debora Semeia Takaliuang: Conceptualization, Methodology, Software, Data curation, Writing- Original draft preparation. Rusli Muljadi, Ratna Sutanto: Visualization, Investigation. Rocksy Fransisca: Supervision. Debora Semeia Takaliuang, Rusli Muljadi: Software, Validation. Ratna Sutanto, Debora Semeia Takaliuang: Writing- Reviewing and Editing References Murray ME, Graff RNR, Ross OA, Petersen RC, Duara R, Dickson DW. Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study. Lancet Neurol. 2011;10(9): 785-96. Tesia AS, Paul SA, Laurel AB, David AB, Suzanne C, Anne MF, et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7 (3): 280-92. Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB,et al. 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1","display":"","copyAsset":false,"role":"figure","size":256146,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u0026nbsp;\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7953365/v1/e1ad0603d511384859dc7c1c.png"},{"id":94633786,"identity":"010bb0c9-857e-43f5-86a1-f0790b32ae67","added_by":"auto","created_at":"2025-10-29 06:39:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":252730,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u0026nbsp;\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7953365/v1/914f85f02dd7eebefbfcc297.png"},{"id":103056289,"identity":"d37a1c29-88bd-4a9f-aa54-f44466068c27","added_by":"auto","created_at":"2026-02-20 09:04:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1134683,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7953365/v1/6d43820b-c2c5-45f6-8647-175fa8698a30.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eCorrelation between mesial temporal atrophy visual scale, hippocampal volumetry, and inferior lateral ventricle-hippocampus ratio in patients with Alzheimer’s dementia\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDementia is a multifactorial neurodegenerative disorder affecting approximately 47\u0026nbsp;million people worldwide, projected to reach 131\u0026nbsp;million by 2050. In the United States, its prevalence is estimated at 10% among individuals aged\u0026thinsp;\u0026gt;\u0026thinsp;65 years, with Alzheimer\u0026rsquo;s disease being the most common cause in this group\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Progressive neuronal loss in AD results from the accumulation of abnormal proteins and neurodegenerative pathology. Given the limited regenerative capacity of aging neurons, early detection is crucial for improving clinical outcomes.\u003csup\u003e\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eHippocampal volume is a major imaging biomarker in AD, yet its quantitative measurement is time-consuming and may be influenced by cranial size. Scheltens et al. (1992) introduced the Medial Temporal Atrophy (MTA) visual scale as a semi-quantitative method for visually grading hippocampal atrophy, with sensitivity and specificity of 75% and 85%, respectively, for differentiating AD from healthy controls.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn addition to hippocampal atrophy, the ratio between hippocampal and inferior lateral ventricle (ILV) volumes has emerged as an important marker in AD, distinguishing true hippocampal atrophy from congenital variants.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e However, early AD presents subtle changes, and visual detection of hippocampal atrophy can be challenging due to its small structure. Harper et al. (2015) reported satisfactory inter-reader reliability for MTA scoring (ICC\u0026thinsp;=\u0026thinsp;0.8) and global cortical atrophy (ICC\u0026thinsp;=\u0026thinsp;0.6)\u003csup\u003e7,8\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eQuantitative medial temporal lobe atrophy (QMTA) measurements based on hippocampal and ILV volumes have demonstrated good diagnostic accuracy. A meta-analysis by Park et al. (2022) reported pooled sensitivity and specificity of 82% and 87% for hippocampal volumetry in differentiating AD from healthy controls.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThis study aimed to assess the correlation between MTA visual scale, hippocampal volume, and ILV/HPC ratio in Alzheimer\u0026rsquo;s disease patients. Establishing this relationship may facilitate more practical and reproducible MRI-based evaluation tools for clinicians and radiologists, supporting early diagnosis and longitudinal monitoring of neurodegenerative disorders.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Design\u003c/h2\u003e\n \u003cp\u003eThis ambispective study combined retrospective and prospective data of Alzheimer\u0026rsquo;s disease patients who underwent conventional brain MRI with a 3D T1-weighted Turbo Field Echo (TFE) sequence between January 2022 and July 2025. The study was approved by the Ethics Committee of the Faculty of Medicine, Universitas Pelita Harapan (Approval No. 219/K-LKJ/ETIK/VI/2025).\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eMTA Visual Scale Assessment\u003c/h3\u003e\n\u003cp\u003eThe MTA visual score was assessed on coronal T1-3D TFE images aligned parallel to the brainstem at the level of the anterior pons. Two radiologists and one senior radiology resident independently rated each case. In case of discrepancy, the senior radiologist determined the final score.\u003c/p\u003e\n\u003ch3\u003eVolumetric Measurement\u003c/h3\u003e\n\u003cp\u003eHippocampal and inferior lateral ventricle volumetric data were obtained from T1-3D TFE images processed using VolBrain software. Absolute volumes were segmented automatically and normalized to intracranial volume (ICV), yielding relative hippocampal and ILV fractions (% of ICV). The ILV/HPC ratio was calculated as:\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003eStatistical Analysis\u003c/h2\u003e\n \u003cp\u003eStatistical analyses were performed using SPSS 26.0. Inter-reader reliability was evaluated with Cohen\u0026rsquo;s \u0026kappa;. Correlations between variables were analyzed using Spearman\u0026rsquo;s \u0026rho;. Variables with p\u0026thinsp;\u0026le;\u0026thinsp;0.25 in bivariate analysis were included in multivariate linear regression models. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003eStudy Population\u003c/h2\u003e\n \u003cp\u003eA total of 36 patients met the inclusion criteria (19 females [52.8%], 17 males [47.2%]). The majority were aged 75\u0026ndash;84 years (41.7%), consistent with the typical demographic profile of Alzheimer\u0026rsquo;s disease (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSample characteristic\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (Min\u0026ndash;Max)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;65 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (19.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65\u0026ndash;74 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (36.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u0026ndash;84 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15 (41.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;85 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (2.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMTA Visual Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 (0\u0026ndash;4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eILV Volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24 (0.68\u0026ndash;6.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHippocampal Volume\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17 (0.35\u0026ndash;7.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eILV/HPC Ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49 (0.11\u0026ndash;1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026mdash;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eInter-reader reliability\u003c/h3\u003e\n\u003cp\u003eCohen\u0026rsquo;s \u0026kappa; values indicated almost perfect agreement between all rater pairs: Reader 1 vs 2\u0026thinsp;=\u0026thinsp;0.852, Reader 2 vs 3\u0026thinsp;=\u0026thinsp;0.889, and Reader 1 vs 3\u0026thinsp;=\u0026thinsp;0.851 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all), according to Landis and Koch (1977).\u003c/p\u003e\n\u003ch3\u003eCorellation analyses\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003e\u0026bull; MTA vs Hippocampal Volume:\u003c/h2\u003e\n \u003cp\u003eModerate negative correlation (r = \u0026minus;\u0026thinsp;0.341; p\u0026thinsp;=\u0026thinsp;0.042). Increasing MTA score was associated with decreasing hippocampal volume (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e\u0026bull; MTA vs ILV/HPC Ratio:\u003c/h2\u003e\n \u003cp\u003eVery strong positive correlation (r\u0026thinsp;=\u0026thinsp;0.843; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating that higher MTA scores correspond to greater relative enlargement of the ILV compared to hippocampal volume (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eMultivariate analysis\u003c/h2\u003e\n \u003cp\u003eMultiple linear regression identified hippocampal volume (B = \u0026minus;\u0026thinsp;0.289; p\u0026thinsp;=\u0026thinsp;0.032) and ILV volume (B\u0026thinsp;=\u0026thinsp;0.586; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as independent predictors of MTA visual score. The model explained 61.6% of the variance (R\u0026sup2; = 0.616).\u003c/p\u003e\n \u003cp\u003eMTA Score\u0026thinsp;=\u0026thinsp;2.026\u0026thinsp;\u0026minus;\u0026thinsp;0.289(Hippocampal Volume)\u0026thinsp;+\u0026thinsp;0.586(ILV Volume)\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eDemographic and biological characteristics\u003c/h2\u003e\u003cp\u003eThis study included 36 participants, consisting of 19 females (52.78%) and 17 males (47.22%). Although the difference was relatively small, females slightly predominated. This finding aligns with prior studies by Oveisgharan et al. (2018)\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, Boccalini et al. (2025)\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, and Buckley et al. (2019)\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e, supporting neuropathological evidence that women tend to exhibit a higher burden of neurofibrillary tau tangles (NFTs) and faster tau accumulation compared with men, both in presymptomatic and symptomatic stages of Alzheimer\u0026rsquo;s dementia.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePathophysiologically, several mechanisms may underlie this observation. First, hormonal factors, particularly the postmenopausal decline in estrogen, eliminate neuroprotective effects such as regulation of cerebral glucose metabolism, inhibition of tau phosphorylation, and modulation of neuroinflammation. This promotes tau hyperphosphorylation and accelerates NFT formation. Second, genetic factors contribute significantly, female carriers of the APOE ε4 allele demonstrate greater tau accumulation and faster progression than male carriers. Third, postmortem neuropathological studies have shown higher NFT density in females even when amyloid load or overall atrophy levels are comparable to males. These findings collectively support the hypothesis that biological differences\u0026mdash;including hormonal, genetic, and metabolic factors\u0026mdash;underlie women\u0026rsquo;s increased vulnerability to Alzheimer\u0026rsquo;s dementia in both preclinical and clinical phases.\u003csup\u003e10\u0026minus;3\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe prevalence of Alzheimer\u0026rsquo;s dementia increases sharply with age. In this study, the largest age group was 75\u0026ndash;84 years (41.67%), consistent with European meta-analyses showing a steep risk escalation in this range, where incidence rises from 3.4 per 1,000 person-years at ages 65\u0026ndash;74 to 13.8 at 75\u0026ndash;84 years and 35.8 among individuals\u0026thinsp;\u0026ge;\u0026thinsp;85 years.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Only one participant (2.78%) in this study was older than 85 years, while the 75\u0026ndash;84 year group dominated the sample (41.67%). This underrepresentation of the oldest-old population is consistent with global Alzheimer\u0026rsquo;s research trends, where individuals\u0026thinsp;\u0026ge;\u0026thinsp;85 years comprise only about 8% of clinical trial participants despite representing the majority of affected patients.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eSeveral factors may explain the low representation of subjects\u0026thinsp;\u0026gt;\u0026thinsp;85 years, including strict exclusion criteria to maintain sample homogeneity and the reluctance of elderly participants or their families due to physical burden and health risks, as also reported by Newmark et al. (2020)\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eInter-Rater Reliability\u003c/h2\u003e\u003cp\u003eInter-rater reliability analysis in this study showed Cohen\u0026rsquo;s κ values ranging from 0.85 to 0.88, indicating \u003cem\u003ealmost perfect agreement\u003c/em\u003e between raters. This exceeds the κ range reported by Cavallin et al. (2012) [32] (κ\u0026thinsp;=\u0026thinsp;0.29\u0026ndash;0.48) and by Rhodius et al. (2017)\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e (κ\u0026thinsp;\u0026asymp;\u0026thinsp;0.80). These findings are comparable to the cohort study by Molinder et al. (2021)\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, which reported κ\u0026thinsp;=\u0026thinsp;0.83\u0026ndash;0.87.\u003c/p\u003e\u003cp\u003eDespite one reader being a senior radiology resident and the others experienced radiologists from different departments, inter-rater consistency remained high. This emphasizes that the standardized MTA visual rating method can minimize variability across different levels of expertise, consistent with Hakansson et al. (2021)\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAlthough high κ values indicate strong reliability, interpretation must remain cautious. As McHugh (2012)\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e [63] noted, even κ values of 0.80\u0026ndash;0.90, classified as \u0026ldquo;almost perfect,\u0026rdquo; represent actual agreement in only 64\u0026ndash;81% of cases\u0026mdash;meaning up to 36% of assessments may still differ. Therefore, while κ\u0026thinsp;\u0026ge;\u0026thinsp;0.80 is acceptable in clinical research, it should not be viewed as absolute proof of validity. Visual rating, though practical, remains subjective. Quantitative approaches (such as hippocampal volumetry or automated segmentation tools) show strong correlation with visual scores but cannot fully replace categorical agreement analysis; both should be applied complementarily\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation Between MTA Visual Scale and Hippocampal Volumetry\u003c/h2\u003e\u003cp\u003eMagnetic field strength differences between 1.5 T and 3 T MRI scanners may introduce bias in volumetric or visual MTA analyses. The 3 T MRI provides a higher signal-to-noise ratio and better anatomical delineation than 1.5 T, making automatic segmentation and visual scoring potentially more sensitive.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eTo minimize discrepancies, this study employed a standardized T1-3D Turbo Field Echo (TFE) isotropic acquisition protocol across both scanners. Furthermore, VolBrain software integrated the international Neuroimaging Consortium for the Evaluation of Alzheimer\u0026rsquo;s (NICE) protocol and adhered to the EADC\u0026ndash;ADNI Harmonized Protocol (HarP) for hippocampal segmentation, improving inter-scanner consistency [51, 65, 66]. VolBrain also provides high reproducibility with shorter processing time, making it a reliable primary quantification tool.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA statistically significant moderate negative correlation was found between visual MTA scores and hippocampal volume (r = \u0026minus;\u0026thinsp;0.341; p\u0026thinsp;=\u0026thinsp;0.042), indicating that higher MTA scores correspond to smaller hippocampal volumes. This finding aligns with Wittens et al. (2024)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.The MTA visual scale reflects not only hippocampal shrinkage but also the expansion of adjacent cerebrospinal fluid spaces (choroid fissure, hippocampal fissure, and inferior lateral ventricle), which may enlarge due to global atrophy.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eDhikav et al. (2017)\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e and Cavedo et al. (2014)\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e also reported significant correlations in Alzheimer\u0026rsquo;s dementia but not in healthy controls. Stronger correlations tend to appear in advanced disease stages, whereas early-stage patients show weaker associations. This suggests that the MTA scale is more sensitive for detecting structural changes in moderate to advanced Alzheimer\u0026rsquo;s disease.\u003c/p\u003e\u003cp\u003eNevertheless, the moderate correlation observed in this study implies that MTA scores and hippocampal volume are not fully interchangeable. MTA grading reflects broader medial temporal changes beyond hippocampal size, and factors such as individual anatomy, disease stage, and tissue hydration may influence correlation strength.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Despite these limitations, the clinical validity of the MTA visual scale remains well-supported by post-mortem confirmation studies\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e, reaffirming its utility as a rapid clinical screening tool, though not a substitute for quantitative hippocampal volumetry.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eCorrelation Between MTA Visual Scale and Inferior Lateral Ventricle\u0026ndash;Hippocampus Ratio\u003c/h2\u003e\u003cp\u003eA very strong positive correlation was observed between MTA visual scores and the inferior lateral ventricle\u0026ndash;hippocampus (ILV/HPC) ratio (r\u0026thinsp;=\u0026thinsp;0.843; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating that more severe medial temporal atrophy (higher MTA score) corresponds to greater relative ILV enlargement compared with hippocampal volume.\u003c/p\u003e\u003cp\u003eThis finding is consistent with Wittens et al. (2024)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, who demonstrated that the ILV/HPC ratio can serve as a quantitative parameter complementary to MTA visual grading, providing a simple alternative for clinical assessment of medial temporal atrophy. Nestor et al. (2008)\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e also reported that lateral ventricular enlargement, particularly in the inferior horn, strongly correlates with hippocampal atrophy and Alzheimer\u0026rsquo;s progression. Similarly, Rusinek et al. (2019)\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e found that the ILV/HPC ratio is an effective atrophy indicator, with sensitivity and specificity of 74%.\u003c/p\u003e\u003cp\u003eRecent studies by Witten et al. (2024)\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e, Lozano et al. (2023)\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e, and Shen et al. (2023)\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e further suggest that the ILV/HPC ratio may outperform absolute hippocampal volume alone, as it accounts for relative structural balance between the hippocampus and surrounding ventricles, making it more dynamic and sensitive to progressive changes.\u003c/p\u003e\u003cp\u003eTo the best of our knowledge, previous studies have predominantly focused on the relationship between the MTA scale and absolute hippocampal volume, whereas the ILV/HPC ratio as an alternative indicator has been rarely explored. In Indonesia, local studies have so far evaluated hippocampal volumetry and ventricular enlargement separately without integrating both parameters into a unified ratio. Therefore, this study provides an important contribution to the regional literature by highlighting the ILV/HPC ratio as a potential quantitative biomarker for assessing medial temporal atrophy in Alzheimer\u0026rsquo;s dementia.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eMultivariate Analysis and Clinical Implications\u003c/h2\u003e\u003cp\u003eMultivariate regression analysis identified hippocampal and inferior lateral ventricle volumes as independent predictors of MTA visual scores, explaining approximately 62% of score variance. These findings confirm that MTA grading predominantly reflects true structural atrophy rather than age-related volume loss. Age and the ILV/HPC ratio did not contribute significantly once absolute volumetric variables were included, indicating their interdependence. The inverse relationship between hippocampal volume and MTA score reinforces the neuropathologic continuum of AD, while the direct association between ILV size and MTA underscores ex vacuo dilatation secondary to parenchymal loss. Clinically, these results validate the combined use of visual and quantitative assessments: visual MTA scoring for rapid screening and volumetric analysis for objective follow-up or research endpoints.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eTechnical Considerations\u003c/h2\u003e\u003cp\u003eMRI field strength (1.5 T vs 3 T) can introduce bias in volumetric estimation due to differing signal-to-noise ratios and spatial resolution. This study minimized variability using standardized T1-3D TFE isotropic sequences and VolBrain\u0026rsquo;s harmonized processing pipeline (EADC-ADNI HarP protocol [51,65,66]), ensuring inter-scanner consistency.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eThis single-center ambispective study had a modest sample size, with unequal distribution between 1.5 T (n\u0026thinsp;=\u0026thinsp;13) and 3 T (n\u0026thinsp;=\u0026thinsp;23) MRI data, potentially introducing bias. Although harmonized acquisition and volumetric normalization (ICV) were applied, future studies should employ uniform scanner strength and larger, multi-center cohorts to improve generalizability.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe MTA visual scale shows a moderate negative correlation with hippocampal volume (r = \u0026minus;\u0026thinsp;0.341; p\u0026thinsp;=\u0026thinsp;0.042).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eA very strong positive correlation exists between the MTA visual scale and the ILV/HPC ratio (r\u0026thinsp;=\u0026thinsp;0.843; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eBoth hippocampal and ILV volumes are independent predictors of MTA score, together explaining 61.6% of its variance.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eThe ILV/HPC ratio offers a quantitative complement to the MTA visual scale, providing a rapid and reliable MRI biomarker for assessing medial temporal atrophy in Alzheimer\u0026rsquo;s disease.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDebora Semeia Takaliuang: Conceptualization, Methodology, Software, Data curation, Writing- Original draft preparation. Rusli Muljadi, Ratna Sutanto: Visualization, Investigation. Rocksy Fransisca: Supervision. Debora Semeia Takaliuang, Rusli Muljadi: Software, Validation. Ratna Sutanto, Debora Semeia Takaliuang: Writing- Reviewing and Editing\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMurray ME, Graff RNR, Ross OA, Petersen RC, Duara R, Dickson DW. Neuropathologically defined subtypes of Alzheimer\u0026apos;s disease with distinct clinical characteristics: a retrospective study. Lancet Neurol. 2011;10(9): 785-96.\u003c/li\u003e\n\u003cli\u003eTesia AS, Paul SA, Laurel AB, David AB, Suzanne C, Anne MF, et al. Toward defining the preclinical stages of Alzheimer\u0026apos;s disease: recommendations from the National Institute on Aging-Alzheimer\u0026apos;s Association workgroups on diagnostic guidelines for Alzheimer\u0026apos;s disease. Alzheimers Dement. 2011;\u003cstrong\u003e7\u003c/strong\u003e(3): 280-92.\u003c/li\u003e\n\u003cli\u003eJack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB,et al. Toward a biological definition of Alzheimer\u0026apos;s disease. Alzheimers Dement. 2018;14(4):535-62.\u003c/li\u003e\n\u003cli\u003eAmerican College of Radiology. ACR Appropriateness Criteria\u0026reg; Dementia. American College of Radiology. Available from https://acsearch.acr.org/docs/3111292/Narrative/. Accessed 11 Nov 2024.\u003c/li\u003e\n\u003cli\u003eRau A, Urbach H. The MTA score-simple and reliable, the best for now? Eur Radiol. 2021;31(12):9057-9.\u003c/li\u003e\n\u003cli\u003eScheltens P, Leys D, Barkhof F, et al. Atrophy of medial temporal lobes on MRI in probable Alzheimer\u0026rsquo;s disease and normal ageing: diagnostic value and neuropsychological correlates. J Neurol Neurosurg Psychiatry. 1992;55:967\u0026ndash;72. \u003c/li\u003e\n\u003cli\u003eWittens MMJ, Allemeersch GJ, Sima DM, Vanderhasselt T, Raeymaeckers S, Fransen E, et al. Towards validation in clinical routine: a comparative analysis of visual MTA ratings versus the automated ratio between inferior lateral ventricle and hippocampal volumes in Alzheimer\u0026apos;s disease diagnosis. Neuroradiology. 2024 Apr;66(4):487-506. \u003c/li\u003e\n\u003cli\u003ePark HY, Suh CH, Heo H, Shim WH, Kim SJ. Diagnostic performance of hippocampal volumetry in Alzheimer\u0026apos;s disease or mild cognitive impairment: a meta-analysis. Eur Radiol. 2022 Oct;32(10):6979-91. \u003c/li\u003e\n\u003cli\u003eMai Y, Cao Z, Zhao L, et al. The role of visual rating and automated brain volumetry in early detection and differential diagnosis of Alzheimer\u0026apos;s disease. CNS Neurosci Ther. 2023; 30(1):e14492.\u003c/li\u003e\n\u003cli\u003eOveisgharan S, Arvanitakis Z, Yu L, Farfel J, Schneider JA, Bennett DA. Sex differences in Alzheimer\u0026apos;s disease and common neuropathologies of aging. Acta Neuropathol. 2018 Dec;136(6):887-900. \u003c/li\u003e\n\u003cli\u003eBoccalini C, Peretti DE, Scheffler M, Mu L, Griffa A, Testart N, et al. Sex differences in the association of Alzheimer\u0026apos;s disease biomarkers and cognition in a multicenter memory clinic study. Alzheimers Res Ther. 2025 Feb 18;17(1):46.\u003c/li\u003e\n\u003cli\u003eBuckley RF, Mormino EC, Rabin JS, Hohman TJ, Landau S, Hanseeuw BJ, et al. Sex differences in the association of global amyloid and regional tau deposition measured by positron emission tomography in clinically normal older adults. \u003cem\u003eJAMA Neurol\u003c/em\u003e. 2019;76(5):542-51.\u003c/li\u003e\n\u003cli\u003eMurn F, Loncar L, Lenicek Krleza J, Roic G, Hojsak I, Misak Z, et al. Volumetric analysis of motor cortex and basal ganglia in pediatric celiac disease patients using volBrain: implications for neurological dysfunction-preliminary results. Diagnostics (Basel). 2024;14(22):2559.\u003c/li\u003e\n\u003cli\u003eTahami Monfared AA, Byrnes MJ, White LA, Zhang Q. Alzheimer\u0026apos;s disease: epidemiology and clinical progression. Neurol Ther. 2022;11(2):553-69.\u003c/li\u003e\n\u003cli\u003eBanzi R, Camaioni P, Tettamanti M, Bertele V, Lucca U. Older patients are still under-represented in clinical trials of Alzheimer\u0026apos;s disease. Alzheimers Res Ther. 2016;8(1):32.\u003c/li\u003e\n\u003cli\u003eNewmark J, Gebara MA, Aizenstein H, Karp JF. Engaging in late-life mental health research: a narrative review of challenges to participation. Curr Treat Options Psychiatry. 2020;7(3):317-36.\u003c/li\u003e\n\u003cli\u003eRhodius-Meester HFM, Benedictus MR, Wattjes MP, Barkhof F, Scheltens P, M\u0026uuml;ller M, et al. MRI visual ratings of brain atrophy and white matter hyperintensities across the spectrum of cognitive decline are differently affected by age and diagnosis. \u003cem\u003eNeurobiol Aging\u003c/em\u003e. 2017;59:41\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eMolinder A, Ziegelitz D, Maier SE, Eckerstr\u0026ouml;m C. Validity and reliability of the medial temporal lobe atrophy scale in a memory clinic population. BMC Neurol. 2021;21(1):289.\u003c/li\u003e\n\u003cli\u003eHakansson C, Tamaddon A, Andersson H, Torisson G, M\u0026aring;rtensson G, Truong M, et al. Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience. Eur Radiol. 2022;32(2):1127-34.\u003c/li\u003e\n\u003cli\u003eTakao H, et al\u003cem\u003e. \u003cem\u003eEffect of scanner in longitudinal studies of brain volume changes.\u003c/em\u003e \u003c/em\u003eJ Magn Reson Imaging. 2011.\u003c/li\u003e\n\u003cli\u003eManj\u0026oacute;n JV, Coup\u0026eacute; P. volBrain: An Online MRI Brain Volumetry System. Front Neuroinform. 2016;10:30.\u003c/li\u003e\n\u003cli\u003eDhikav V, Duraiswamy S, Anand KS. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer\u0026apos;s disease. Ann Indian Acad Neurol. 2017;20(1):29-35.\u003c/li\u003e\n\u003cli\u003eCavedo E, Redolfi A, Angeloni F, Babiloni C, Lizio R, Chiapparini L, et al. The Italian Alzheimer\u0026apos;s Disease Neuroimaging Initiative (I-ADNI): validation of structural MR imaging. J Alzheimers Dis. 2014;40(4):941-52.\u003c/li\u003e\n\u003cli\u003eDhikav V, Duraiswamy S, Anand KS. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer\u0026apos;s disease. Ann Indian Acad Neurol. 2017;20(1):29-35.\u003c/li\u003e\n\u003cli\u003eNguyen TT, Zhang H, Leung KK, Chen L, Mok VCT, Wong A, et al. Correlation between visual medial temporal atrophy score and hippocampal subregion volumetry in Alzheimer\u0026rsquo;s disease. \u003cem\u003eBrain Sci Adv\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e 2024;10(1):21\u0026ndash;31.\u003c/li\u003e\n\u003cli\u003eTrasch\u0026uuml;tz A, Enkirch SJ, Polomac N, Widmann CN, Schild HH, Heneka MT, Hattingen E. The Entorhinal Cortex Atrophy Score Is Diagnostic and Prognostic in Mild Cognitive Impairment. J Alzheimers Dis. 2020;75(1):99-108.\u003c/li\u003e\n\u003cli\u003eNestor SM, Rupsingh R, Borrie M, et al. Ventricular enlargement as a possible measure of Alzheimer\u0026apos;s disease progression validated using the Alzheimer\u0026apos;s disease neuroimaging initiative database. Brain. 2008;131(9):2443-54.\u003c/li\u003e\n\u003cli\u003eRusinek H, Endo Y, De Santi S, Frid D, Tsui WH, Segal S, et al. Atrophy of hippocampal formation and inferior lateral ventricle: Diagnostic accuracy in Alzheimer\u0026rsquo;s disease. \u003cem\u003eNeurobiol Aging\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e 2019;84:47\u0026ndash;55.\u003c/li\u003e\n\u003cli\u003eLozano FC, Rey IR, Balo LA, Calvo PC, Rey G, Sanz B, et al. Hippocampal‐to‐ventricle ratio outperforms hippocampal volume as a marker of cognitive impairment across the lifespan. \u003cem\u003eAlzheimers Dement\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e 2023;19(S5):e079039. \u003c/li\u003e\n\u003cli\u003eShen X, Liu K, Cui D, Wu Y, Li Y, Wang Y, et al. Hippocampal‐to‐ventricle ratio: a sensitive biomarker for brain aging and cognitive decline. \u003cem\u003eBrain Behav\u003c/em\u003e. 2023;13(2):e2925.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"mesial temporal atrophy, hippocampal volumetry, inferior lateral ventricle, inferior lateral ventricle–hippocampus ratio","lastPublishedDoi":"10.21203/rs.3.rs-7953365/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7953365/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eAlzheimer\u0026rsquo;s dementia is characterized by hippocampal atrophy and enlargement of the lateral ventricles, particularly the inferior portion. The visual assessment of medial temporal atrophy using the Mesial Temporal Atrophy (MTA) scale is commonly employed due to its simplicity; however, it remains subjective. Quantitative measurements of hippocampal volume and the inferior lateral ventricle\u0026ndash;hippocampus ratio offer a more objective quantitative approach.\u003c/p\u003e\u003ch2\u003eObjective:\u003c/h2\u003e\u003cp\u003eTo evaluate the correlation between the MTA visual scale, hippocampal volumetry, and the inferior lateral ventricle\u0026ndash;hippocampus ratio in patients with Alzheimer\u0026rsquo;s dementia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eAn ambispective study was conducted from January 2022 to July 2025. Subjects were patients with Alzheimer\u0026rsquo;s dementia who underwent brain MRI with T1-3D TFE sequences. The MTA visual scale was assessed independently by three readers. Hippocampal and inferior lateral ventricle volumetric analyses were performed using \u003cem\u003eVolBrain\u003c/em\u003e software. Inter-reader reliability was assessed using Cohen\u0026rsquo;s κ, while correlations between variables were analyzed using Spearman\u0026rsquo;s test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 36 subjects met the inclusion criteria. Inter-reader agreement was almost perfect (Cohen\u0026rsquo;s κ\u0026thinsp;=\u0026thinsp;0.851\u0026ndash;0.889). A moderate negative correlation was found between the MTA visual scale and hippocampal volumetry (r = \u0026minus;\u0026thinsp;0.341; p\u0026thinsp;=\u0026thinsp;0.042), a very strong positive correlation between the MTA visual scale and the inferior lateral ventricle\u0026ndash;hippocampus ratio (r\u0026thinsp;=\u0026thinsp;0.843; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and a moderate negative correlation between hippocampal volumetry and the inferior lateral ventricle\u0026ndash;hippocampus ratio (r = \u0026minus;\u0026thinsp;0.483; p\u0026thinsp;=\u0026thinsp;0.003). Multivariate analysis showed that hippocampal and inferior lateral ventricle measurements were significant predictors of MTA score, contributing to 61.6% of its variance (R\u0026sup2; = 0.616).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThere is a significant correlation between the MTA visual scale, hippocampal volumetry, and the inferior lateral ventricle\u0026ndash;hippocampus ratio. The inferior lateral ventricle\u0026ndash;hippocampus ratio demonstrated the strongest correlation with the MTA score and may serve as a simple quantitative biomarker for assessing medial temporal atrophy in Alzheimer\u0026rsquo;s dementia.\u003c/p\u003e","manuscriptTitle":"Correlation between mesial temporal atrophy visual scale, hippocampal volumetry, and inferior lateral ventricle-hippocampus ratio in patients with Alzheimer’s dementia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-29 06:38:59","doi":"10.21203/rs.3.rs-7953365/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":"937264b5-c978-4986-9dfc-be37c2dafa3c","owner":[],"postedDate":"October 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-08T21:08:43+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-29 06:38:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7953365","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7953365","identity":"rs-7953365","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}