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To minimize subjectivity and inter\u2010rater variability, an automated, accurate, precise, and reliable segmentation technique for the hippocampus (HC) and surrounding cerebro\u2010spinal fluid (CSF) filled spaces\u2014such as the temporal horns of the lateral ventricles\u2014is essential. We trained and evaluated three automated methods for the segmentation of both HC and CSF (Multi\u2010Atlas Label Fusion (MALF), Nonlinear Patch\u2010Based Segmentation (NLPB), and a Convolutional Neural Network (CNN)). We then evaluated these methods, including the widely used <jats:italic>FreeSurfer<\/jats:italic> technique, using baseline T1w MRIs of 1641 participants from the AD Neuroimaging Initiative study with various degree of atrophy associated with their cognitive status on the spectrum from cognitively healthy to clinically probable AD. Our gold standard consisted in manual segmentation of HC and CSF from 80 cognitively healthy individuals. We calculated HC volumes and HVR and compared all methods in terms of segmentation reliability, similarity across methods, sensitivity in detecting between\u2010group differences and associations with age, scores of the learning subtest of the Rey Auditory Verbal Learning Test (RAVLT) and the Alzheimer's Disease Assessment Scale 13 (ADAS13) scores. Cross validation demonstrated that the CNN method yielded more accurate HC and CSF segmentations when compared to MALF and NLPB, demonstrating higher volumetric overlap (Dice Kappa\u2009=\u20090.94) and correlation (rho\u2009=\u20090.99) with the manual labels. It was also the most reliable method in clinical data application, showing minimal failures. Our comparisons yielded high correlations between FreeSurfer, CNN and NLPB volumetric values. HVR yielded higher control:AD effect sizes than HC volumes among all segmentation methods, reinforcing the significance of HVR in clinical distinction. The positive association with age was significantly stronger for HVR compared to HC volumes on all methods except FreeSurfer. Memory associations with HC volumes or HVR were only significant for individuals with mild cognitive impairment. Finally, the HC volumes and HVR showed comparable negative associations with ADAS13, particularly in the mild cognitive impairment cohort. This study provides an evaluation of automated segmentation methods centered to estimate HVR, emphasizing the superior performance of a CNN\u2010based algorithm. The findings underscore the pivotal role of accurate segmentation in HVR calculations for precise clinical applications, contributing valuable insights into medial temporal lobe atrophy in neurodegenerative disorders, especially AD.<\/jats:p>","DOI":"10.1002\/hbm.70265","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T12:22:50Z","timestamp":1754050970000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enhanced Detection of Age\u2010Related and Cognitive Declines Using Automated Hippocampal\u2010To\u2010Ventricle Ratio in Alzheimer's Patients"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2288-8111","authenticated-orcid":false,"given":"Sofia","family":"Fernandez\u2010Lozano","sequence":"first","affiliation":[{"name":"McConnell Brain Imaging Centre Montreal Neurological Institute, McGill University  Montreal Quebec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Fonov","sequence":"additional","affiliation":[{"name":"McConnell Brain Imaging Centre Montreal Neurological Institute, McGill University  Montreal Quebec Canada"},{"name":"Department of Neurology and Neurosurgery McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Schoemaker","sequence":"additional","affiliation":[{"name":"Department of Psychology McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Pruessner","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Konstanz  Konstanz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Potvin","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Research Institute  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Duchesne","sequence":"additional","affiliation":[{"name":"Quebec Heart and Lung Research Institute  Quebec City Quebec Canada"},{"name":"Radiology and Nuclear Medicine Department Universit\u00e9 Laval  Quebec City Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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