MRI-based correlations of mesial temporal atrophy, hippocampal volumetry, and inferior lateral ventricle–hippocampus ratio in Alzheimer’s dementia

MRI-based correlations of mesial temporal atrophy, hippocampal volumetry, and inferior lateral ventricle–hippocampus ratio in 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 Article MRI-based correlations of mesial temporal atrophy, hippocampal volumetry, and inferior lateral ventricle–hippocampus ratio in Alzheimer’s dementia debora semeia takaliuang, Rusli Muljadi, Ratna Sutanto, Rocksy Situmeang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8824555/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 16 You are reading this latest preprint version Abstract Background Alzheimer’s dementia (AD) is characterized by medial temporal lobe atrophy, particularly involving the hippocampus, and secondary enlargement of the inferior lateral ventricles. The Mesial Temporal Atrophy (MTA) visual scale is widely used in clinical practice but is inherently subjective, while quantitative MRI-based measurements may provide greater objectivity. Objective To evaluate the correlation between the MTA visual scale, hippocampal volumetry, and the inferior lateral ventricle–hippocampus (ILV/HPC) ratio in patients with Alzheimer’s dementia. Methods This ambispective study included thirty-six patients with Alzheimer’s dementia who underwent brain MRI between January 2022 and July 2025. Visual MTA scoring and automated volumetric measurements of the hippocampus and inferior lateral ventricle were performed. Inter-reader reliability and correlations between imaging parameters were statistically analyzed. Results Thirty-six patients were included. Inter-reader agreement for MTA scoring was almost perfect (Cohen’s κ = 0.851–0.889). The MTA score showed a moderate negative correlation with hippocampal volume (r = − 0.341; p = 0.042) and a very strong positive correlation with the ILV/HPC ratio (r = + 0.843; p < 0.001). Multivariate analysis demonstrated that hippocampal and inferior lateral ventricle volumes were independent predictors of MTA score (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. Health sciences/Diseases Health sciences/Medical research Health sciences/Neurology Biological sciences/Neuroscience mesial temporal atrophy hippocampal volumetry inferior lateral ventricle inferior lateral ventricle–hippocampus ratio Figures Figure 1 Figure 2 Background Alzheimer’s disease is the leading cause of dementia in older adults, characterized by progressive neurodegeneration and neuronal loss. Early and accurate diagnosis is essential, as timely intervention can improve clinical outcomes in a brain with limited regenerative capacity. Structural MRI provides key biomarkers for AD, particularly in the medial temporal lobe.[ 1 – 3 ] Medial temporal lobe atrophy, especially hippocampal atrophy, is a hallmark imaging feature and correlates with cognitive decline. Hippocampal volumetry is a well-established quantitative method to measure atrophy but is time-consuming, requires specialized software, and is influenced by individual anatomical variability, such as cranial size. The MTA visual scale offers a simple, semi-quantitative alternative with good diagnostic performance; however, it remains subjective and may be less sensitive in early disease stages[ 4 , 5 ]. In addition to hippocampal atrophy, enlargement of the inferior lateral ventricle reflects secondary ex-vacuo dilatation due to adjacent hippocampal loss. The ILV/HPC ratio, which combines hippocampal volume and ventricular size, has been proposed as a complementary biomarker. This ratio may offer several advantages over hippocampal volume alone. By considering ventricular size relative to hippocampal volume, it accounts for differences in cranial size and individual anatomical variation. Moreover, early neurodegenerative changes may lead to noticeable ventricular expansion before absolute hippocampal volume loss becomes pronounced, enhancing sensitivity to subtle atrophy. Finally, using a ratio improves reproducibility by reducing the influence of absolute volumetric measurement errors, potentially minimizing inter-rater variability [ 6 – 9 ]. Therefore, this study aimed to evaluate the correlation between the MTA visual scale, hippocampal volumetry, and the ILV/HPC ratio in patients with Alzheimer’s disease. We hypothesize that MTA visual scores correlate with both hippocampal volume and ILV/HPC ratio, and that the ILV/HPC ratio may provide a more robust and objective measure of medial temporal atrophy than hippocampal volume alone. Subjects and Methods Study Design This ambispective study combined retrospective and prospective data of Alzheimer’s disease patients who underwent brain MRI with a 3D T1-weighted Turbo Field Echo (TFE) sequence using 1.5 T and 3 T MRI (Philips Achieva). To minimize scanner-related variability, all volumetric measurements were processed using the same automated pipeline and normalized to intracranial volume. Specifically, 20 patients were identified retrospectively from medical records between January 2022 – October 2024, while 16 patients were enrolled prospectively from November 2024 to July 2025. The study was approved by the Ethics Committee of the Faculty of Medicine, Pelita Harapan University (Approval No. 219/K-LKJ/ETIK/VI/2025). All methods were performed in accordance with the relevant guidelines and regulations.f Patients were included if they had been clinically diagnosed with Alzheimer’s dementia by a board-certified neurologist based on clinical evaluation and standardized cognitive or memory testing. As supportive diagnostic evidence, a subset of patients (n = 12) also underwent amyloid positron emission tomography imaging demonstrating amyloid positivity consistent with Alzheimer’s disease pathology. Eligible participants were required to have complete MRI data suitable for MTA assessment and volumetric analysis. Patients were excluded if they had a diagnosis of vascular dementia or a history or imaging evidence of cerebral infarction involving subcortical structures, the perihippocampal region, or the medial temporal lobe. Additional exclusion criteria included a history of intracranial tumors, prior brain surgery, or the presence of cerebral microbleeds detected on susceptibility-weighted imaging. Patients with incomplete medical records or insufficient imaging data were also excluded from the analysis. 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 board-certified radiologists (with 30 and 22 years of experience in neuroradiology and one senior radiology resident (with 4 years of training) independently rated each case. In case of discrepancy, the senior radiologist determined the final score. All raters were blinded to the clinical data and final diagnosis. 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 inferior lateral ventricle fractions (% of ICV). The ILV/HPC ratio was calculated by dividing the inferior lateral ventricle volume by the hippocampal volume, with both volumes normalized to intracranial volume (%ICV). Automated volumetric segmentation of the hippocampus and inferior lateral ventricle was performed using VolBrain software, which has been previously validated against expert manual segmentation. To ensure segmentation quality, all volumetric outputs were visually inspected for gross segmentation errors, including mislabeling or incomplete delineation of structures. Cases with inadequate segmentation quality or significant technical artifacts were excluded from the final analysis. 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. Data distribution was assessed using the Shapiro–Wilk test. As several variables showed non-normal distribution, non-parametric statistical methods were applied. Outliers were evaluated visually using boxplots and were retained in the analysis unless attributable to clear technical or segmentation errors, which were excluded during quality control. 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 ). 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). Correlation analyses • MTA vs Hippocampal Volume: Moderate negative correlation (r = − 0.341; 95% CI: −0.58 to − 0.02; p = 0.042) which means increasing MTA score was associated with decreasing hippocampal volume (Fig. 1 ). • MTA vs ILV/HPC Ratio: Very strong positive correlation (r = + 0.843; 95% CI: 0.70 to 0.92; 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; 95% CI: −0.55 to − 0.03; p = 0.032) and ILV volume (B = 0.586; 95% CI: 0.34 to 0.83; 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 This study evaluated the relationship between MTA grading and quantitative MRI-derived parameters, namely hippocampal volume and the inferior lateral ventricle–hippocampus ILV/HPC ratio, in patients with Alzheimer’s dementia. The results demonstrated a moderate inverse negative correlation between MTA scores and hippocampal volume, a very strong positive correlation scores between MTA scores and the ILV/HPC ratio, and excellent inter-rater reliability of visual MTA assessment. In terms of demographic characteristics, females slightly predominated (52.8%). This finding is consistent with previous studies reporting a higher prevalence and faster pathological progression of Alzheimer’s dementia in women, which has been attributed to hormonal, genetic, and neuropathological factors, including a greater burden of neurofibrillary tau pathology and faster tau accumulation compared with men [ 10 – 13 ]. Beside that, postmortem neuropathological studies have shown higher NFT density in females even when amyloid load or overall atrophy levels are comparable to males[ 12 , 13 ]. The most common age group in this study was 75–84 years, aligning with epidemiological data showing a sharp increase in Alzheimer’s incidence in this age range [ 14 , 15 ]. The relatively small proportion of patients aged ≥ 85 years reflects common recruitment challenges in advanced age groups, as reported in prior studies [ 16 ]. Inter-reader reliability analysis demonstrated almost perfect agreement, with Cohen’s κ values ranging from 0.85 to 0.89. These results are comparable to those reported by Molinder et al[ 19 ] and exceed agreement levels described in earlier studies[ 17 , 18 ]. The high consistency observed despite differing levels of reader experience supports the robustness and reproducibility of standardized MTA visual assessment in clinical practice. This emphasizes that the standardized MTA visual rating method can minimize variability across different levels of expertise, consistent with Hakansson et al[ 20 ]. The moderate inverse association between MTA score and hippocampal volume (r = − 0.341; 95% CI: −0.58 to − 0.02; p = 0.042) indicates that higher MTA grades reflect reduced hippocampal size but are not solely determined by hippocampal volume. This is consistent with previous studies showing that the MTA scale captures a composite of medial temporal changes, including hippocampal shrinkage and enlargement of adjacent cerebrospinal fluid spaces such as the choroid fissure and inferior lateral ventricle [ 7 , 23 , 24 ]. Consequently, MTA grading and hippocampal volumetry should be regarded as complementary rather than interchangeable markers. In contrast, the ILV/HPC ratio demonstrated a very strong positive correlation with MTA scores (r = + 0.843; 95% CI: 0.70 to 0.92; p < 0.001), suggesting that this ratio closely reflects the visual components assessed in MTA grading. This finding is in line with Wittens et al. [ 7 ], Nestor et al. [ 27 ], and Rusinek et al. [ 28 ], who reported that inferior lateral ventricular enlargement is tightly linked to hippocampal atrophy and disease progression in Alzheimer’s dementia. By incorporating both ventricular expansion and hippocampal loss, the ILV/HPC ratio appears to provide a more balanced and dynamic representation of medial temporal structural change than absolute hippocampal volume alone. Multivariate regression analysis further supported this interpretation, identifying hippocampal volume and inferior lateral ventricle volume as independent predictors of MTA score, together explaining approximately 61.6% of its variance. These results indicate that visual MTA grading predominantly reflects true neurodegenerative changes rather than age-related volume variation, reinforcing its biological validity. From a clinical perspective, these findings support the continued use of the MTA visual scale as a rapid and reliable screening tool in routine practice, particularly in settings where advanced post-processing is not readily available. The strong correlation between MTA scores and the ILV/HPC ratio suggests that this ratio may serve as a simple quantitative adjunct, offering greater objectivity while remaining feasible for clinical implementation. Such an approach may be especially useful for longitudinal follow-up and research applications. Technical Considerations 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 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. VolBrain also provides high reproducibility with shorter processing time, making it a reliable primary quantification tool[ 22 , 23 ]. 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, ensuring inter-scanner consistency. Limitations This study has several limitations. First, it was a single-center ambispective study with a modest sample size and an unequal distribution of MRI field strengths, with 1.5 T scanners used in 13 patients and 3 T scanners in 23 patients, which may limit generalizability and introduce potential scanner-related bias. Although standardized acquisition protocols and intracranial volume normalization were applied to mitigate variability, residual effects related to field strength differences cannot be fully excluded. Second, the cross-sectional design precludes assessment of longitudinal changes in medial temporal atrophy and disease progression. Future multicenter studies with larger cohorts, uniform scanner strength, and longitudinal follow-up are warranted to validate the ILV/HPC ratio as a biomarker of disease progression and clinical outcomes. Future Research Future multicenter studies with larger, more diverse cohorts, uniform imaging protocols, and longitudinal follow-up are warranted to validate the ILV/HPC ratio as a biomarker of disease progression and clinical outcomes. Conclusion The present study demonstrated a moderate negative correlation between the Mesial Temporal Atrophy (MTA) visual scale and hippocampal volume, indicating that higher MTA scores are associated with smaller hippocampal volumes. In contrast, a very strong positive correlation was observed between MTA scores and the inferior lateral ventricle–hippocampus (ILV/HPC) ratio, suggesting that increasing medial temporal atrophy is accompanied by a disproportionate enlargement of the inferior lateral ventricle relative to hippocampal size. Multivariate analysis further confirmed that hippocampal volume and inferior lateral ventricle volume were independent predictors of the MTA visual score, together accounting for 61.6% of its variance. Overall, these findings suggest that the ILV/HPC ratio shows promise as a quantitative complement to visual MTA assessment for evaluating medial temporal atrophy in Alzheimer’s disease. However, larger studies with independent cohorts are warranted to further validate its clinical utility and generalizability. Abbreviations ADNI Alzheimer’s Disease Neuroimaging Initiative EADC European Alzheimer’s Disease Consortium HPC Hippocampus ICV Intracranial Volume ILV Inferior Lateral Ventricle MRI Magnetic Resonance Imaging MTA Mesial Temporal Atrophy NFT Neurofibrillary Tau NICE Neuroimaging Consortium for the Evaluation of Alzheimer’s TFE Turbo filed echo T1 WI-T1 Weighted Image Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the Faculty of Medicine, Pelita Harapan University (Approval No. 219/K-LKJ/ETIK/VI/2025). All methods were performed in accordance with the relevant guidelines and regulations. Written informed consent was obtained from all participants or their legally authorized representatives for the prospective component of the study. For the retrospective component, the requirement for informed consent was waived by the Ethics Committee due to the use of fully anonymized data. Consent for publication Not applicable. Competing interest The authors declare no competing interests. Funding The authors declare that this research received no external funding. 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, Cucunawangsih: Writing- Reviewing and Editing References Wu, J. et al. A systematic analysis of diagnostic performance for Alzheimer's disease using structural MRI. Psychoradiology 2 (1), 1–9 (2022). Márquez, F. & Yassa, M. A. Neuroimaging biomarkers for Alzheimer’s disease. Mol. Neurodegener . 14 , 21 (2019). Jack, C. R. et al. Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 14 (4), 535–562 (2018). American College of Radiology. ACR Appropriateness Criteria® Dementia. Reston (VA): American College of Radiology; c2024 [cited 2024 Nov 11]. Available from: https://acsearch.acr.org/docs/3111292/Narrative/ Rau, A. & Urbach, H. The MTA score-simple and reliable, the best for now? Eur. Radiol. 31 (12), 9057–9059 (2021). Scheltens, P. et al. Atrophy of medial temporal lobes on MRI in probable Alzheimer’s disease and normal ageing: diagnostic value and neuropsychological correlates. J. Neurol. Neurosurg. Psychiatry . 55 , 967–972 (1992). Wittens, M. M. J. 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's disease diagnosis. Neuroradiology 66 (4), 487–506 (2024). Park, H. Y., Suh, C. H., Heo, H., Shim, W. H. & Kim, S. J. Diagnostic performance of hippocampal volumetry in Alzheimer's disease or mild cognitive impairment: a meta-analysis. Eur. Radiol. 32 (10), 6979–6991 (2022). Mai, Y. et al. 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A. & Zhang, Q. Alzheimer's disease: epidemiology and clinical progression. Neurol. Ther. 11 (2), 553–569 (2022). Banzi, R., Camaioni, P., Tettamanti, M., Bertele, V. & Lucca, U. Older patients are still under-represented in clinical trials of Alzheimer's disease. Alzheimers Res. Ther. 8 (1), 32 (2016). Newmark, J., Gebara, M. A., Aizenstein, H. & Karp, J. F. Engaging in late-life mental health research: a narrative review of challenges to participation. Curr. Treat. Options Psychiatry . 7 (3), 317–336 (2020). Cavallin, L. et al. Overtime reliability of medial temporal lobe atrophy rating in a clinical setting. Acta Radiol. 53 , 318–323 (2012). Rhodius-Meester, H. F. 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. Neurobiol. Aging . 59 , 41–49 (2017). Molinder, A., Ziegelitz, D., Maier, S. E. & Eckerström, C. Validity and reliability of the medial temporal lobe atrophy scale in a memory clinic population. BMC Neurol. 21 (1), 289 (2021). Hakansson, C. 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. 32 (2), 1127–1134 (2022). Takao, H. et al. Effect of scanner in longitudinal studies of brain volume changes. J. Magn. Reson. Imaging . 34 (2), 438–444 (2011). Manjón, J. V., Coupé, P. & volBrain An Online MRI Brain Volumetry System. Front. Neuroinform . 10 , 30 (2016). Cavedo, E. et al. The Italian Alzheimer's Disease Neuroimaging Initiative (I-ADNI): validation of structural MR imaging. J. Alzheimers Dis. 40 (4), 941–952 (2014). Dhikav, V., Duraiswamy, S. & Anand, K. S. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease. Ann. Indian Acad. Neurol. 20 (1), 29–35 (2017). Nguyen, T. T. et al. Correlation between visual medial temporal atrophy score and hippocampal subregion volumetry in Alzheimer’s disease. Brain Sci. Adv. 10 (1), 21–31 (2024). Traschütz, A. et al. The Entorhinal Cortex Atrophy Score Is Diagnostic and Prognostic in Mild Cognitive Impairment. J. Alzheimers Dis. 75 (1), 99–108 (2020). Nestor, S. M. et al. Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database. Brain 131 (9), 2443–2454 (2008). Rusinek, H. et al. Atrophy of hippocampal formation and inferior lateral ventricle: Diagnostic accuracy in Alzheimer’s disease. Neurobiol. Aging . 84 , 47–55 (2019). Lozano, F. C. et al. Hippocampal-to‐ventricle ratio outperforms hippocampal volume as a marker of cognitive impairment across the lifespan. Alzheimers Dement. 19 (S5), e079039 (2023). Shen, X. et al. Hippocampal-to‐ventricle ratio: a sensitive biomarker for brain aging and cognitive decline. Brain Behav. 13 (2), e2925 (2023). Tables Table 1 Sample characteristic Characteristic Mean ± SD (Min–Max) n (%) Age (years) — 85 years — 1 (3%) Sex distribution Female — 19 (53%) Male — 17 (47%) Scanner type 1.5 T Phillips 13 (36%) 3 T Phillips 23 (64%) 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) — Additional Declarations No competing interests reported. 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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-8824555","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":623366256,"identity":"f592b471-58b4-465c-bd42-a58ff26be3c7","order_by":0,"name":"debora semeia takaliuang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABHUlEQVRIiWNgGAWjYDCCAzwQWoKBueEAiMEPIhIKCGoxAGphhGiRbABpMSBSC1jA4ABEACfgO9578HFFzR95yfaDjYd5au7YbT6/OvHDAwMGeX6xA1i1SJ45l2x45piB4WyexIbDPMeeJW+78XazBNBhhjNnJ2DVYnAjx0yygc2AcR4DSAvb4WSzG2c3gLQkGNzGoeX+G6CWfwb28/gfArX8O5xsPOPs5h94tdzgMZNsbDNInC0BtIW37bCdAX/vNry2SJ7JSzZs7DNOnjnjYcPBuX2HEyRu8G6zSDCQwOkXvuNnDz5s+CZnO+N88uEPb74dtufvP7v55o8KG3l+aexaMEBigwRYpQRxykHAnoH/APGqR8EoGAWjYEQAAGyZa8yt4wW3AAAAAElFTkSuQmCC","orcid":"","institution":"Pelita Harapan University","correspondingAuthor":true,"prefix":"","firstName":"debora","middleName":"semeia","lastName":"takaliuang","suffix":""},{"id":623366257,"identity":"48954513-c873-4ec9-a5aa-f567db376228","order_by":1,"name":"Rusli Muljadi","email":"","orcid":"","institution":"Pelita Harapan University","correspondingAuthor":false,"prefix":"","firstName":"Rusli","middleName":"","lastName":"Muljadi","suffix":""},{"id":623366258,"identity":"9a1ab982-f643-4b16-87fc-5fd8ca7641fd","order_by":2,"name":"Ratna Sutanto","email":"","orcid":"","institution":"Pelita Harapan University","correspondingAuthor":false,"prefix":"","firstName":"Ratna","middleName":"","lastName":"Sutanto","suffix":""},{"id":623366259,"identity":"fa263cd4-795b-4829-b730-6f494c14f356","order_by":3,"name":"Rocksy Situmeang","email":"","orcid":"","institution":"Pelita Harapan University","correspondingAuthor":false,"prefix":"","firstName":"Rocksy","middleName":"","lastName":"Situmeang","suffix":""},{"id":623366260,"identity":"8b5637bc-1276-47f9-b80d-bac6741986e6","order_by":4,"name":"- cucunawangsih","email":"","orcid":"","institution":"Pelita Harapan University","correspondingAuthor":false,"prefix":"","firstName":"-","middleName":"","lastName":"cucunawangsih","suffix":""}],"badges":[],"createdAt":"2026-02-09 00:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8824555/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8824555/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107482772,"identity":"9e7c3cda-ec67-4e5b-aded-f6b214550081","added_by":"auto","created_at":"2026-04-22 02:24:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":106310,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot showing the correlation between the visual MTA scale and hippocampal volumetry. Each circular dot represents an individual subject (patient) with corresponding values of the visual MTA scale and hippocampal volume. The curved line in the middle indicates the local regression line, illustrating the general relationship pattern between the visual MTA scale and hippocampal volumetry, demonstrating a trend of decreasing hippocampal volume with increasing visual MTA scale scores.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8824555/v1/75199b62ab6f39dccdb6fabd.png"},{"id":107256394,"identity":"e59015c2-14fb-4d74-87fb-1cb4ef50aebc","added_by":"auto","created_at":"2026-04-19 12:16:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":8888,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot showing the correlation between the visual MTA scale and the inferior lateral ventricle–hippocampus ratio.Each circular dot represents an individual subject (patient) with corresponding values of the visual MTA scale and the inferior lateral ventricle–hippocampus ratio. The curved line in the middle illustrates a positive relationship between the MTA scale and the inferior lateral ventricle–hippocampus ratio, indicating that hippocampal atrophy is associated with a relative enlargement of the inferior lateral ventricle.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8824555/v1/69a9be51afd428a1924bd240.jpg"},{"id":107705060,"identity":"4e8dc3e6-1bb7-455d-a6d5-200fea0feaab","added_by":"auto","created_at":"2026-04-24 09:07:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":345206,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8824555/v1/8dda93dd-39e1-4fc6-a70b-4e03ec6ed87c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"MRI-based correlations of mesial temporal atrophy, hippocampal volumetry, and inferior lateral ventricle–hippocampus ratio in Alzheimer’s dementia","fulltext":[{"header":"Background","content":"\u003cp\u003eAlzheimer\u0026rsquo;s disease is the leading cause of dementia in older adults, characterized by progressive neurodegeneration and neuronal loss. Early and accurate diagnosis is essential, as timely intervention can improve clinical outcomes in a brain with limited regenerative capacity. Structural MRI provides key biomarkers for AD, particularly in the medial temporal lobe.[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMedial temporal lobe atrophy, especially hippocampal atrophy, is a hallmark imaging feature and correlates with cognitive decline. Hippocampal volumetry is a well-established quantitative method to measure atrophy but is time-consuming, requires specialized software, and is influenced by individual anatomical variability, such as cranial size. The MTA visual scale offers a simple, semi-quantitative alternative with good diagnostic performance; however, it remains subjective and may be less sensitive in early disease stages[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn addition to hippocampal atrophy, enlargement of the inferior lateral ventricle reflects secondary ex-vacuo dilatation due to adjacent hippocampal loss. The ILV/HPC ratio, which combines hippocampal volume and ventricular size, has been proposed as a complementary biomarker. This ratio may offer several advantages over hippocampal volume alone. By considering ventricular size relative to hippocampal volume, it accounts for differences in cranial size and individual anatomical variation. Moreover, early neurodegenerative changes may lead to noticeable ventricular expansion before absolute hippocampal volume loss becomes pronounced, enhancing sensitivity to subtle atrophy. Finally, using a ratio improves reproducibility by reducing the influence of absolute volumetric measurement errors, potentially minimizing inter-rater variability [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherefore, this study aimed to evaluate the correlation between the MTA visual scale, hippocampal volumetry, and the ILV/HPC ratio in patients with Alzheimer\u0026rsquo;s disease. We hypothesize that MTA visual scores correlate with both hippocampal volume and ILV/HPC ratio, and that the ILV/HPC ratio may provide a more robust and objective measure of medial temporal atrophy than hippocampal volume alone.\u003c/p\u003e"},{"header":"Subjects and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis ambispective study combined retrospective and prospective data of Alzheimer\u0026rsquo;s disease patients who underwent brain MRI with a 3D T1-weighted Turbo Field Echo (TFE) sequence using 1.5 T and 3 T MRI (Philips Achieva). To minimize scanner-related variability, all volumetric measurements were processed using the same automated pipeline and normalized to intracranial volume. Specifically, 20 patients were identified retrospectively from medical records between January 2022 \u0026ndash; October 2024, while 16 patients were enrolled prospectively from November 2024 to July 2025. The study was approved by the Ethics Committee of the Faculty of Medicine, Pelita Harapan University (Approval No. 219/K-LKJ/ETIK/VI/2025). All methods were performed in accordance with the relevant guidelines and regulations.f\u003c/p\u003e \u003cp\u003ePatients were included if they had been clinically diagnosed with Alzheimer\u0026rsquo;s dementia by a board-certified neurologist based on clinical evaluation and standardized cognitive or memory testing. As supportive diagnostic evidence, a subset of patients (n\u0026thinsp;=\u0026thinsp;12) also underwent amyloid positron emission tomography imaging demonstrating amyloid positivity consistent with Alzheimer\u0026rsquo;s disease pathology. Eligible participants were required to have complete MRI data suitable for MTA assessment and volumetric analysis. Patients were excluded if they had a diagnosis of vascular dementia or a history or imaging evidence of cerebral infarction involving subcortical structures, the perihippocampal region, or the medial temporal lobe. Additional exclusion criteria included a history of intracranial tumors, prior brain surgery, or the presence of cerebral microbleeds detected on susceptibility-weighted imaging. Patients with incomplete medical records or insufficient imaging data were also excluded from the analysis.\u003c/p\u003e \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 board-certified radiologists (with 30 and 22 years of experience in neuroradiology and one senior radiology resident (with 4 years of training) independently rated each case. In case of discrepancy, the senior radiologist determined the final score. All raters were blinded to the clinical data and final diagnosis.\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 inferior lateral ventricle fractions (% of ICV). The ILV/HPC ratio was calculated by dividing the inferior lateral ventricle volume by the hippocampal volume, with both volumes normalized to intracranial volume (%ICV).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAutomated volumetric segmentation of the hippocampus and inferior lateral ventricle was performed using VolBrain software, which has been previously validated against expert manual segmentation. To ensure segmentation quality, all volumetric outputs were visually inspected for gross segmentation errors, including mislabeling or incomplete delineation of structures. Cases with inadequate segmentation quality or significant technical artifacts were excluded from the final analysis.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using SPSS 26.0. Inter-reader reliability was evaluated with Cohen\u0026rsquo;s κ. Correlations between variables were analyzed using Spearman\u0026rsquo;s ρ. 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. Data distribution was assessed using the Shapiro\u0026ndash;Wilk test. As several variables showed non-normal distribution, non-parametric statistical methods were applied. Outliers were evaluated visually using boxplots and were retained in the analysis unless attributable to clear technical or segmentation errors, which were excluded during quality control.\u003c/p\u003e \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\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\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\u003eCorrelation analyses\u003c/h3\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n\u003cp\u003e\u0026bull; MTA vs Hippocampal Volume:\u003c/p\u003e\n\u003cp\u003eModerate negative correlation (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.341; 95% CI: \u0026minus;0.58 to \u0026minus;\u0026thinsp;0.02; p\u0026thinsp;=\u0026thinsp;0.042) which means increasing MTA score was associated with decreasing hippocampal volume (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026bull; MTA vs ILV/HPC Ratio:\u003c/p\u003e\n\u003cp\u003eVery strong positive correlation (r\u0026thinsp;=\u0026thinsp;+\u0026thinsp;0.843; 95% CI: 0.70 to 0.92; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating that higher MTA scores correspond to greater relative enlargement of the ILV compared to hippocampal volume (Fig.\u0026nbsp;\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\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.289; 95% CI: \u0026minus;0.55 to \u0026minus;\u0026thinsp;0.03; p\u0026thinsp;=\u0026thinsp;0.032) and ILV volume (B\u0026thinsp;=\u0026thinsp;0.586; 95% CI: 0.34 to 0.83; 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":"\u003cp\u003eThis study evaluated the relationship between MTA grading and quantitative MRI-derived parameters, namely hippocampal volume and the inferior lateral ventricle\u0026ndash;hippocampus ILV/HPC ratio, in patients with Alzheimer\u0026rsquo;s dementia. The results demonstrated a moderate inverse negative correlation between MTA scores and hippocampal volume, a very strong positive correlation scores between MTA scores and the ILV/HPC ratio, and excellent inter-rater reliability of visual MTA assessment.\u003c/p\u003e \u003cp\u003eIn terms of demographic characteristics, females slightly predominated (52.8%). This finding is consistent with previous studies reporting a higher prevalence and faster pathological progression of Alzheimer\u0026rsquo;s dementia in women, which has been attributed to hormonal, genetic, and neuropathological factors, including a greater burden of neurofibrillary tau pathology and faster tau accumulation compared with men [\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Beside that, postmortem neuropathological studies have shown higher NFT density in females even when amyloid load or overall atrophy levels are comparable to males[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe most common age group in this study was 75\u0026ndash;84 years, aligning with epidemiological data showing a sharp increase in Alzheimer\u0026rsquo;s incidence in this age range [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The relatively small proportion of patients aged\u0026thinsp;\u0026ge;\u0026thinsp;85 years reflects common recruitment challenges in advanced age groups, as reported in prior studies [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e Inter-reader reliability analysis demonstrated almost perfect agreement, with Cohen\u0026rsquo;s κ values ranging from 0.85 to 0.89. These results are comparable to those reported by Molinder et al[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and exceed agreement levels described in earlier studies[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The high consistency observed despite differing levels of reader experience supports the robustness and reproducibility of standardized MTA visual assessment in clinical practice. This emphasizes that the standardized MTA visual rating method can minimize variability across different levels of expertise, consistent with Hakansson et al[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe moderate inverse association between MTA score and hippocampal volume (r\u0026thinsp;=\u0026thinsp;\u0026minus;\u0026thinsp;0.341; 95% CI: \u0026minus;0.58 to \u0026minus;\u0026thinsp;0.02; p\u0026thinsp;=\u0026thinsp;0.042) indicates that higher MTA grades reflect reduced hippocampal size but are not solely determined by hippocampal volume. This is consistent with previous studies showing that the MTA scale captures a composite of medial temporal changes, including hippocampal shrinkage and enlargement of adjacent cerebrospinal fluid spaces such as the choroid fissure and inferior lateral ventricle [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Consequently, MTA grading and hippocampal volumetry should be regarded as complementary rather than interchangeable markers.\u003c/p\u003e\u003cp\u003eIn contrast, the ILV/HPC ratio demonstrated a very strong positive correlation with MTA scores (r\u0026thinsp;=\u0026thinsp;+\u0026thinsp;0.843; 95% CI: 0.70 to 0.92; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), suggesting that this ratio closely reflects the visual components assessed in MTA grading. This finding is in line with Wittens et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], Nestor et al. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], and Rusinek et al. [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], who reported that inferior lateral ventricular enlargement is tightly linked to hippocampal atrophy and disease progression in Alzheimer\u0026rsquo;s dementia. By incorporating both ventricular expansion and hippocampal loss, the ILV/HPC ratio appears to provide a more balanced and dynamic representation of medial temporal structural change than absolute hippocampal volume alone.\u003c/p\u003e \u003cp\u003eMultivariate regression analysis further supported this interpretation, identifying hippocampal volume and inferior lateral ventricle volume as independent predictors of MTA score, together explaining approximately 61.6% of its variance. These results indicate that visual MTA grading predominantly reflects true neurodegenerative changes rather than age-related volume variation, reinforcing its biological validity.\u003c/p\u003e \u003cp\u003eFrom a clinical perspective, these findings support the continued use of the MTA visual scale as a rapid and reliable screening tool in routine practice, particularly in settings where advanced post-processing is not readily available. The strong correlation between MTA scores and the ILV/HPC ratio suggests that this ratio may serve as a simple quantitative adjunct, offering greater objectivity while remaining feasible for clinical implementation. Such an approach may be especially useful for longitudinal follow-up and research applications.\u003c/p\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eTechnical Considerations\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[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. To minimize discrepancies, this study employed a standardized T1-3D 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. VolBrain also provides high reproducibility with shorter processing time, making it a reliable primary quantification tool[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\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, ensuring inter-scanner consistency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study has several limitations. First, it was a single-center ambispective study with a modest sample size and an unequal distribution of MRI field strengths, with 1.5 T scanners used in 13 patients and 3 T scanners in 23 patients, which may limit generalizability and introduce potential scanner-related bias. Although standardized acquisition protocols and intracranial volume normalization were applied to mitigate variability, residual effects related to field strength differences cannot be fully excluded. Second, the cross-sectional design precludes assessment of longitudinal changes in medial temporal atrophy and disease progression. Future multicenter studies with larger cohorts, uniform scanner strength, and longitudinal follow-up are warranted to validate the ILV/HPC ratio as a biomarker of disease progression and clinical outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eFuture Research\u003c/h2\u003e \u003cp\u003eFuture multicenter studies with larger, more diverse cohorts, uniform imaging protocols, and longitudinal follow-up are warranted to validate the ILV/HPC ratio as a biomarker of disease progression and clinical outcomes.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe present study demonstrated a moderate negative correlation between the Mesial Temporal Atrophy (MTA) visual scale and hippocampal volume, indicating that higher MTA scores are associated with smaller hippocampal volumes. In contrast, a very strong positive correlation was observed between MTA scores and the inferior lateral ventricle\u0026ndash;hippocampus (ILV/HPC) ratio, suggesting that increasing medial temporal atrophy is accompanied by a disproportionate enlargement of the inferior lateral ventricle relative to hippocampal size. Multivariate analysis further confirmed that hippocampal volume and inferior lateral ventricle volume were independent predictors of the MTA visual score, together accounting for 61.6% of its variance. Overall, these findings suggest that the ILV/HPC ratio shows promise as a quantitative complement to visual MTA assessment for evaluating medial temporal atrophy in Alzheimer\u0026rsquo;s disease. However, larger studies with independent cohorts are warranted to further validate its clinical utility and generalizability.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADNI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlzheimer\u0026rsquo;s Disease Neuroimaging Initiative\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEADC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEuropean Alzheimer\u0026rsquo;s Disease Consortium\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHPC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHippocampus\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eICV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntracranial Volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eILV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInferior Lateral Ventricle\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMTA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMesial Temporal Atrophy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNFT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeurofibrillary Tau\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNICE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeuroimaging Consortium for the Evaluation of Alzheimer\u0026rsquo;s\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTFE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eTurbo filed echo\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWI-T1 Weighted Image\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e \u003cp\u003e This study was approved by the Ethics Committee of the Faculty of Medicine, Pelita Harapan University (Approval No. 219/K-LKJ/ETIK/VI/2025). All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e \u003c/p\u003e\u003cp\u003eWritten informed consent was obtained from all participants or their legally authorized representatives for the prospective component of the study. For the retrospective component, the requirement for informed consent was waived by the Ethics Committee due to the use of fully anonymized data.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e \u003ch2\u003eConsent for publication\u003c/h2\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interest\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors declare that this research received no external funding.\u003c/p\u003e\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, Cucunawangsih: Writing- Reviewing and Editing\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWu, J. et al. A systematic analysis of diagnostic performance for Alzheimer's disease using structural MRI. \u003cem\u003ePsychoradiology\u003c/em\u003e \u003cb\u003e2\u003c/b\u003e (1), 1\u0026ndash;9 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eM\u0026aacute;rquez, F. \u0026amp; Yassa, M. A. Neuroimaging biomarkers for Alzheimer\u0026rsquo;s disease. \u003cem\u003eMol. Neurodegener\u003c/em\u003e. \u003cb\u003e14\u003c/b\u003e, 21 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJack, C. R. et al. Toward a biological definition of Alzheimer's disease. \u003cem\u003eAlzheimers Dement.\u003c/em\u003e \u003cb\u003e14\u003c/b\u003e (4), 535\u0026ndash;562 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmerican College of Radiology. ACR Appropriateness Criteria\u0026reg; Dementia. Reston (VA): American College of Radiology; c2024 [cited 2024 Nov 11]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://acsearch.acr.org/docs/3111292/Narrative/\u003c/span\u003e\u003cspan address=\"https://acsearch.acr.org/docs/3111292/Narrative/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRau, A. \u0026amp; Urbach, H. The MTA score-simple and reliable, the best for now? \u003cem\u003eEur. Radiol.\u003c/em\u003e \u003cb\u003e31\u003c/b\u003e (12), 9057\u0026ndash;9059 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScheltens, P. et al. Atrophy of medial temporal lobes on MRI in probable Alzheimer\u0026rsquo;s disease and normal ageing: diagnostic value and neuropsychological correlates. \u003cem\u003eJ. Neurol. Neurosurg. 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Ther.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e (2), 553\u0026ndash;569 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBanzi, R., Camaioni, P., Tettamanti, M., Bertele, V. \u0026amp; Lucca, U. Older patients are still under-represented in clinical trials of Alzheimer's disease. \u003cem\u003eAlzheimers Res. Ther.\u003c/em\u003e \u003cb\u003e8\u003c/b\u003e (1), 32 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNewmark, J., Gebara, M. A., Aizenstein, H. \u0026amp; Karp, J. F. Engaging in late-life mental health research: a narrative review of challenges to participation. \u003cem\u003eCurr. Treat. Options Psychiatry\u003c/em\u003e. \u003cb\u003e7\u003c/b\u003e (3), 317\u0026ndash;336 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavallin, L. et al. Overtime reliability of medial temporal lobe atrophy rating in a clinical setting. \u003cem\u003eActa Radiol.\u003c/em\u003e \u003cb\u003e53\u003c/b\u003e, 318\u0026ndash;323 (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRhodius-Meester, H. F. 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. \u003cb\u003e59\u003c/b\u003e, 41\u0026ndash;49 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMolinder, A., Ziegelitz, D., Maier, S. E. \u0026amp; Eckerstr\u0026ouml;m, C. Validity and reliability of the medial temporal lobe atrophy scale in a memory clinic population. \u003cem\u003eBMC Neurol.\u003c/em\u003e \u003cb\u003e21\u003c/b\u003e (1), 289 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHakansson, C. 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. \u003cem\u003eEur. Radiol.\u003c/em\u003e \u003cb\u003e32\u003c/b\u003e (2), 1127\u0026ndash;1134 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakao, H. et al. Effect of scanner in longitudinal studies of brain volume changes. \u003cem\u003eJ. Magn. Reson. Imaging\u003c/em\u003e. \u003cb\u003e34\u003c/b\u003e (2), 438\u0026ndash;444 (2011).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManj\u0026oacute;n, J. V., Coup\u0026eacute;, P. \u0026amp; volBrain An Online MRI Brain Volumetry System. \u003cem\u003eFront. Neuroinform\u003c/em\u003e. \u003cb\u003e10\u003c/b\u003e, 30 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavedo, E. et al. The Italian Alzheimer's Disease Neuroimaging Initiative (I-ADNI): validation of structural MR imaging. \u003cem\u003eJ. Alzheimers Dis.\u003c/em\u003e \u003cb\u003e40\u003c/b\u003e (4), 941\u0026ndash;952 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDhikav, V., Duraiswamy, S. \u0026amp; Anand, K. S. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease. \u003cem\u003eAnn. Indian Acad. Neurol.\u003c/em\u003e \u003cb\u003e20\u003c/b\u003e (1), 29\u0026ndash;35 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen, T. T. 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 \u003cb\u003e10\u003c/b\u003e (1), 21\u0026ndash;31 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrasch\u0026uuml;tz, A. et al. The Entorhinal Cortex Atrophy Score Is Diagnostic and Prognostic in Mild Cognitive Impairment. \u003cem\u003eJ. Alzheimers Dis.\u003c/em\u003e \u003cb\u003e75\u003c/b\u003e (1), 99\u0026ndash;108 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNestor, S. M. et al. Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database. \u003cem\u003eBrain\u003c/em\u003e \u003cb\u003e131\u003c/b\u003e (9), 2443\u0026ndash;2454 (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRusinek, H. et al. Atrophy of hippocampal formation and inferior lateral ventricle: Diagnostic accuracy in Alzheimer\u0026rsquo;s disease. \u003cem\u003eNeurobiol. Aging\u003c/em\u003e. \u003cb\u003e84\u003c/b\u003e, 47\u0026ndash;55 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLozano, F. C. et al. Hippocampal-to‐ventricle ratio outperforms hippocampal volume as a marker of cognitive impairment across the lifespan. \u003cem\u003eAlzheimers Dement.\u003c/em\u003e \u003cb\u003e19\u003c/b\u003e (S5), e079039 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen, X. et al. Hippocampal-to‐ventricle ratio: a sensitive biomarker for brain aging and cognitive decline. \u003cem\u003eBrain Behav.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e (2), e2925 (2023).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption\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\u0026nbsp;\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; 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%)\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%)\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 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt; 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 (3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex distribution\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\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\u003e19 (53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\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\u003e17 (47%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eScanner type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.5 T Phillips\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 T Phillips\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23 (64%)\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\u003c/div\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"mesial temporal atrophy, hippocampal volumetry, inferior lateral ventricle, inferior lateral ventricle–hippocampus ratio","lastPublishedDoi":"10.21203/rs.3.rs-8824555/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8824555/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlzheimer’s dementia (AD) is characterized by medial temporal lobe atrophy, particularly involving the hippocampus, and secondary enlargement of the inferior lateral ventricles. The Mesial Temporal Atrophy (MTA) visual scale is widely used in clinical practice but is inherently subjective, while quantitative MRI-based measurements may provide greater objectivity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo evaluate the correlation between the MTA visual scale, hippocampal volumetry, and the inferior lateral ventricle–hippocampus (ILV/HPC) ratio in patients with Alzheimer’s dementia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis ambispective study included thirty-six patients with Alzheimer’s dementia who underwent brain MRI between January 2022 and July 2025. Visual MTA scoring and automated volumetric measurements of the hippocampus and inferior lateral ventricle were performed. Inter-reader reliability and correlations between imaging parameters were statistically analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThirty-six patients were included. Inter-reader agreement for MTA scoring was almost perfect (Cohen’s κ = 0.851–0.889). The MTA score showed a moderate negative correlation with hippocampal volume (r = − 0.341; p = 0.042) and a very strong positive correlation with the ILV/HPC ratio (r = + 0.843; p \u0026lt; 0.001). Multivariate analysis demonstrated that hippocampal and inferior lateral ventricle volumes were independent predictors of MTA score (R² = 0.616).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere 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.\u003c/p\u003e","manuscriptTitle":"MRI-based correlations of mesial temporal atrophy, hippocampal volumetry, and inferior lateral ventricle–hippocampus ratio in Alzheimer’s dementia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 12:16:38","doi":"10.21203/rs.3.rs-8824555/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"330328470171951296893368219475621325283","date":"2026-05-15T09:26:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"19054917895245444883852316250973911224","date":"2026-05-15T07:45:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T09:14:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T09:05:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"330659342949871528005455079680312871213","date":"2026-05-10T17:07:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T20:54:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"238598809973828566435612226082332617482","date":"2026-04-27T17:37:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"220420801071139634283537528054684627627","date":"2026-04-27T06:54:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"203655497313324870076043145987744655466","date":"2026-04-26T16:09:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"74843610060001385888754351563546532391","date":"2026-04-25T15:28:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"22165539816225646555010078515520993574","date":"2026-04-24T19:53:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-09T16:46:25+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-09T16:39:50+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-10T05:47:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-02T16:22:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-03-02T09:55:20+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"937264b5-c978-4986-9dfc-be37c2dafa3c","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"330328470171951296893368219475621325283","date":"2026-05-15T09:26:55+00:00","index":192,"fulltext":""},{"type":"reviewerAgreed","content":"19054917895245444883852316250973911224","date":"2026-05-15T07:45:02+00:00","index":191,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-12T09:14:13+00:00","index":189,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T09:05:09+00:00","index":186,"fulltext":""},{"type":"reviewerAgreed","content":"330659342949871528005455079680312871213","date":"2026-05-10T17:07:28+00:00","index":185,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T20:54:46+00:00","index":172,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":66340076,"name":"Health sciences/Diseases"},{"id":66340077,"name":"Health sciences/Medical research"},{"id":66340078,"name":"Health sciences/Neurology"},{"id":66340079,"name":"Biological sciences/Neuroscience"}],"tags":[],"updatedAt":"2026-04-19T12:16:38+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 12:16:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8824555","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8824555","identity":"rs-8824555","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}