{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:56:34Z","timestamp":1781643394084,"version":"3.54.5"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":47,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cognitive impairment is hallmark of Alzheimer\u2019s disease (AD). Although structural MRI has consistently demonstrated widespread brain atrophy in AD, the comparative utility of different imaging sequences for predicting cognitive decline remains uncertain. The Boundary Shift Integral (BSI), a longitudinal measure quantifying brain volume change over time, provides a dynamic alternative to conventional cross-sectional volumetric measures and could more sensitively reflect cognition-related neurodegeneration. This study investigated the associations between BSI-derived atrophy and domain-specific cognitive performance across the AD continuum. Participants (Cognitively Normal [CN]\u2009=\u2009155, Mild Cognitive Impairment [MCI]\u2009=\u2009283, AD\u2009=\u2009100) underwent comprehensive cognitive testing, and composite scores were computed for memory, executive function, and language domains. BSI metrics for the whole brain, ventricles, and bilateral hippocampi were derived from serial MRI scans acquired at baseline and 12-month follow-up and were directly compared with conventional T1-weighted volumetric measures. Linear regression models were used to examine associations between imaging markers and domain-specific cognitive scores, adjusting for relevant covariates. In the MCI group, BSI measures demonstrated significant associations with all cognitive domains, consistently outperforming traditional volumetric measures. Whole-brain and ventricular BSI were significantly associated with memory, executive function, and language, while hippocampal BSI showed particularly robust associations with memory. In the AD group, BSI again exhibited more consistent associations with cognitive performance than volumetrics, especially for whole-brain and right hippocampal measures. No significant associations were observed in the CN group. Direct comparisons confirmed that BSI provides enhanced sensitivity to cognition-relevant structural changes, particularly in early and prodromal stages of AD. BSI measures offer superior sensitivity in detecting early structural brain changes associated with cognitive decline. These findings support the utility of BSI as a dynamic and clinically relevant tool for early detection and longitudinal monitoring of the disease.<\/jats:p>","DOI":"10.1038\/s41598-026-39465-9","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:51:34Z","timestamp":1773849094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations between ventricular boundary shift integral and composite cognitive domains across the alzheimer\u2019s disease continuum"],"prefix":"10.1038","volume":"16","author":[{"given":"Hamide","family":"Nasiri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannaneh","family":"Azimizonuzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farbod","family":"Khosravi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyedeh Fahimeh","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Khoshrou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Setareh","family":"Rezakhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reyhaneh","family":"Badri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danial","family":"Kazemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negar","family":"Toorani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kobra","family":"Soltanikhadiv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadra","family":"Behrouzieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Mohammad Amin","family":"Alavi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayan","family":"Shakeri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Mayeli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0429-1914","authenticated-orcid":false,"given":"Farshad","family":"Shahkarami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"39465_CR1","doi-asserted-by":"crossref","unstructured":"Weller, J. & Budson, A. Current understanding of Alzheimer\u2019s disease diagnosis and treatment. F1000Res 2018, 7 (2018).","DOI":"10.12688\/f1000research.14506.1"},{"key":"39465_CR2","doi-asserted-by":"publisher","first-page":"37","DOI":"10.2147\/CLEP.S37929","volume":"6","author":"MM Mielke","year":"2014","unstructured":"Mielke, M. M., Vemuri, P. & Rocca, W. A. Clinical epidemiology of alzheimer\u2019s disease: assessing sex and gender differences. Clin. Epidemiol. 6, 37\u201348 (2014).","journal-title":"Clin. Epidemiol."},{"issue":"3","key":"39465_CR3","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3233\/JAD-180766","volume":"67","author":"JL Cummings","year":"2019","unstructured":"Cummings, J. L., Tong, G. & Ballard, C. Treatment combinations for alzheimer\u2019s disease: current and future pharmacotherapy options. J. Alzheimers Dis. 67 (3), 779\u2013794 (2019).","journal-title":"J. Alzheimers Dis."},{"issue":"1","key":"39465_CR4","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/nm.4443","volume":"24","author":"Z He","year":"2018","unstructured":"He, Z. et al. Amyloid-\u03b2 plaques enhance alzheimer\u2019s brain Tau-seeded pathologies by facilitating neuritic plaque Tau aggregation. Nat. Med. 24 (1), 29\u201338 (2018).","journal-title":"Nat. Med."},{"key":"39465_CR5","doi-asserted-by":"crossref","unstructured":"De-Paula, V. J., Radanovic, M., Diniz, B. S. & Forlenza, O. V. Alzheimer\u2019s disease. Subcell. Biochem. 65, 329\u2013352 (2012).","DOI":"10.1007\/978-94-007-5416-4_14"},{"issue":"24","key":"39465_CR6","doi-asserted-by":"publisher","first-page":"5789","DOI":"10.3390\/molecules25245789","volume":"25","author":"Z Breijyeh","year":"2020","unstructured":"Breijyeh, Z. & Karaman, R. Comprehensive review on alzheimer\u2019s disease: causes and treatment. Molecules 25 (24), 5789 (2020).","journal-title":"Molecules"},{"issue":"1","key":"39465_CR7","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/cns.12317","volume":"21","author":"GP Peng","year":"2015","unstructured":"Peng, G. P. et al. Correlation of hippocampal volume and cognitive performances in patients with either mild cognitive impairment or alzheimer\u2019s disease. CNS Neurosci. Ther. 21 (1), 15\u201322 (2015).","journal-title":"CNS Neurosci. Ther."},{"issue":"5","key":"39465_CR8","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1002\/alz.13780","volume":"20","author":"A Kapasi","year":"2024","unstructured":"Kapasi, A. et al. Association between hippocampal microglia, AD and LATE-NC, and cognitive decline in older adults. Alzheimers Dement. 20 (5), 3193\u20133202 (2024).","journal-title":"Alzheimers Dement."},{"issue":"9","key":"39465_CR9","doi-asserted-by":"publisher","first-page":"2702","DOI":"10.1093\/brain\/awq148","volume":"133","author":"MA Parra","year":"2010","unstructured":"Parra, M. A. et al. Visual short-term memory binding deficits in Familial alzheimer\u2019s disease. Brain 133 (9), 2702\u20132713 (2010).","journal-title":"Brain"},{"issue":"1","key":"39465_CR10","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1002\/gps.4703","volume":"33","author":"C Kobylecki","year":"2018","unstructured":"Kobylecki, C. et al. Functional neuroanatomical associations of working memory in early-onset alzheimer\u2019s disease. Int. J. Geriatr. Psychiatry. 33 (1), 176\u2013184 (2018).","journal-title":"Int. J. Geriatr. Psychiatry"},{"issue":"2\u20133","key":"39465_CR11","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1159\/000338233","volume":"33","author":"A Martyr","year":"2012","unstructured":"Martyr, A. & Clare, L. Executive function and activities of daily living in alzheimer\u2019s disease: a correlational meta-analysis. Dement. Geriatr. Cogn. Disord. 33 (2\u20133), 189\u2013203 (2012).","journal-title":"Dement. Geriatr. Cogn. Disord"},{"issue":"1","key":"39465_CR12","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1590\/1980-57642021dn15-010006","volume":"15","author":"NOC Cezar","year":"2021","unstructured":"Cezar, N. O. C. et al. Changes in executive function and gait in people with mild cognitive impairment and alzheimer disease. Dement. Neuropsychol. 15 (1), 60\u201368 (2021).","journal-title":"Dement. Neuropsychol."},{"key":"39465_CR13","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3389\/fnagi.2018.00437","volume":"10","author":"A Guarino","year":"2018","unstructured":"Guarino, A. et al. Executive functions in alzheimer disease: a systematic review. Front. Aging Neurosci. 10, 437 (2018).","journal-title":"Front. Aging Neurosci."},{"issue":"Pt 1","key":"39465_CR14","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1093\/brain\/awr311","volume":"135","author":"ML Schroeter","year":"2012","unstructured":"Schroeter, M. L. et al. Executive deficits are related to the inferior frontal junction in early dementia. Brain 135 (Pt 1), 201\u2013215 (2012).","journal-title":"Brain"},{"issue":"5","key":"39465_CR15","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1080\/13803390701550128","volume":"30","author":"V Taler","year":"2008","unstructured":"Taler, V. & Phillips, N. A. Language performance in alzheimer\u2019s disease and mild cognitive impairment: a comparative review. J. Clin. Exp. Neuropsychol. 30 (5), 501\u2013556 (2008).","journal-title":"J. Clin. Exp. Neuropsychol."},{"issue":"12","key":"39465_CR16","doi-asserted-by":"publisher","first-page":"905","DOI":"10.3109\/02699206.2013.815278","volume":"27","author":"S Pekkala","year":"2013","unstructured":"Pekkala, S. et al. Lexical retrieval in discourse: an early indicator of alzheimer\u2019s dementia. Clin. Linguist Phon. 27 (12), 905\u2013921 (2013).","journal-title":"Clin. Linguist Phon"},{"key":"39465_CR17","doi-asserted-by":"publisher","first-page":"959405","DOI":"10.3389\/fnagi.2022.959405","volume":"14","author":"M Rafiq","year":"2022","unstructured":"Rafiq, M. et al. The functional connectivity of Language network across the life span: disentangling the effects of typical aging from alzheimer\u2019s disease. Front. Aging Neurosci. 14, 959405 (2022).","journal-title":"Front. Aging Neurosci."},{"key":"39465_CR18","doi-asserted-by":"publisher","first-page":"100583","DOI":"10.1016\/j.eclinm.2020.100583","volume":"28","author":"E Eyigoz","year":"2020","unstructured":"Eyigoz, E. et al. Linguistic markers predict onset of alzheimer\u2019s disease. EClinicalMedicine 28, 100583 (2020).","journal-title":"EClinicalMedicine"},{"issue":"1","key":"39465_CR19","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1037\/a0031288","volume":"27","author":"S Ahmed","year":"2013","unstructured":"Ahmed, S., de Jager, C. A., Haigh, A. M. & Garrard, P. Semantic processing in connected speech at a uniformly early stage of autopsy-confirmed alzheimer\u2019s disease. Neuropsychology 27 (1), 79\u201385 (2013).","journal-title":"Neuropsychology"},{"issue":"894","key":"39465_CR20","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1259\/bjr.75.894.750506","volume":"75","author":"KM Bradley","year":"2002","unstructured":"Bradley, K. M. et al. Serial brain MRI at 3\u20136 month intervals as a surrogate marker for alzheimer\u2019s disease. Br. J. Radiol. 75 (894), 506\u2013513 (2002).","journal-title":"Br. J. Radiol."},{"issue":"Suppl 1","key":"39465_CR21","doi-asserted-by":"publisher","first-page":"S81","DOI":"10.1016\/j.neurobiolaging.2014.04.035","volume":"36","author":"F Prados","year":"2015","unstructured":"Prados, F. et al. Measuring brain atrophy with a generalized formulation of the boundary shift integral. Neurobiol. Aging. 36 (Suppl 1), S81\u201390 (2015).","journal-title":"Neurobiol. Aging"},{"issue":"5","key":"39465_CR22","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1109\/42.640753","volume":"16","author":"PA Freeborough","year":"1997","unstructured":"Freeborough, P. A. & Fox, N. C. The boundary shift integral: an accurate and robust measure of cerebral volume changes from registered repeat MRI. IEEE Trans. Med. Imaging. 16 (5), 623\u2013629 (1997).","journal-title":"IEEE Trans. Med. Imaging"},{"issue":"1","key":"39465_CR23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/j.1552-6569.2006.00081.x","volume":"17","author":"VM Anderson","year":"2007","unstructured":"Anderson, V. M. et al. Cerebral atrophy measurement in clinically isolated syndromes and relapsing remitting multiple sclerosis: a comparison of registration-based methods. J. Neuroimaging. 17 (1), 61\u201368 (2007).","journal-title":"J. Neuroimaging"},{"key":"39465_CR24","doi-asserted-by":"publisher","first-page":"102418","DOI":"10.1016\/j.nicl.2020.102418","volume":"28","author":"M Moccia","year":"2020","unstructured":"Moccia, M. et al. Spinal cord atrophy in a primary progressive multiple sclerosis trial: improved sample size using GBSI. Neuroimage Clin. 28, 102418 (2020).","journal-title":"Neuroimage Clin."},{"issue":"3 Suppl","key":"39465_CR25","doi-asserted-by":"publisher","first-page":"11s","DOI":"10.1177\/1051228404266264","volume":"14","author":"D Pelletier","year":"2004","unstructured":"Pelletier, D., Garrison, K. & Henry, R. Measurement of whole-brain atrophy in multiple sclerosis. J. Neuroimaging. 14 (3 Suppl), 11s\u201319s (2004).","journal-title":"J. Neuroimaging"},{"issue":"5","key":"39465_CR26","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1002\/ana.25571","volume":"86","author":"M Moccia","year":"2019","unstructured":"Moccia, M. et al. Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral. Ann. Neurol. 86 (5), 704\u2013713 (2019).","journal-title":"Ann. Neurol."},{"key":"39465_CR27","doi-asserted-by":"publisher","first-page":"120775","DOI":"10.1016\/j.neuroimage.2024.120775","volume":"298","author":"L Luchetti","year":"2024","unstructured":"Luchetti, L. et al. Evaluation of cervical spinal cord atrophy using a modified SIENA approach. Neuroimage 298, 120775 (2024).","journal-title":"Neuroimage"},{"issue":"6","key":"39465_CR28","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1002\/mds.22485","volume":"24","author":"SM Henley","year":"2009","unstructured":"Henley, S. M. et al. Whole-brain atrophy as a measure of progression in premanifest and early huntington\u2019s disease. Mov. Disord. 24 (6), 932\u2013936 (2009).","journal-title":"Mov. Disord"},{"issue":"4","key":"39465_CR29","doi-asserted-by":"publisher","first-page":"1659","DOI":"10.1016\/j.neuroimage.2009.06.003","volume":"47","author":"NZ Hobbs","year":"2009","unstructured":"Hobbs, N. Z. et al. Automated quantification of caudate atrophy by local registration of serial MRI: evaluation and application in huntington\u2019s disease. Neuroimage 47 (4), 1659\u20131665 (2009).","journal-title":"Neuroimage"},{"issue":"7","key":"39465_CR30","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1002\/mds.22969","volume":"25","author":"EJ Wild","year":"2010","unstructured":"Wild, E. J. et al. Rate and acceleration of whole-brain atrophy in premanifest and early huntington\u2019s disease. Mov. Disord.. 25 (7), 888\u2013895 (2010).","journal-title":"Mov. Disord."},{"issue":"7","key":"39465_CR31","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1212\/WNL.0b013e318281ccd3","volume":"80","author":"KK Leung","year":"2013","unstructured":"Leung, K. K. et al. Cerebral atrophy in mild cognitive impairment and alzheimer disease: rates and acceleration. Neurology 80 (7), 648\u2013654 (2013).","journal-title":"Neurology"},{"issue":"4","key":"39465_CR32","doi-asserted-by":"publisher","first-page":"3995","DOI":"10.1016\/j.neuroimage.2011.10.068","volume":"59","author":"KK Leung","year":"2012","unstructured":"Leung, K. K., Ridgway, G. R., Ourselin, S. & Fox, N. C. Consistent multi-time-point brain atrophy estimation from the boundary shift integral. Neuroimage 59 (4), 3995\u20134005 (2012).","journal-title":"Neuroimage"},{"issue":"8","key":"39465_CR33","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1016\/j.neurobiolaging.2013.02.003","volume":"34","author":"J Barnes","year":"2013","unstructured":"Barnes, J. et al. Vascular and alzheimer\u2019s disease markers independently predict brain atrophy rate in alzheimer\u2019s disease neuroimaging initiative controls. Neurobiol. Aging. 34 (8), 1996\u20132002 (2013).","journal-title":"Neurobiol. Aging"},{"issue":"7","key":"39465_CR34","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.neurobiolaging.2010.11.001","volume":"33","author":"VM Anderson","year":"2012","unstructured":"Anderson, V. M. et al. Gray matter atrophy rate as a marker of disease progression in AD. Neurobiol. Aging. 33 (7), 1194\u20131202 (2012).","journal-title":"Neurobiol. Aging"},{"key":"39465_CR35","doi-asserted-by":"publisher","first-page":"1344920","DOI":"10.3389\/fnagi.2024.1344920","volume":"16","author":"Y Hu","year":"2024","unstructured":"Hu, Y., Zhu, T. & Zhang, W. The characteristics of brain atrophy prior to the onset of alzheimer\u2019s disease: a longitudinal study. Front. Aging Neurosci. 16, 1344920 (2024).","journal-title":"Front. Aging Neurosci."},{"issue":"7","key":"39465_CR36","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1212\/WNL.34.7.939","volume":"34","author":"G McKhann","year":"1984","unstructured":"McKhann, G. et al. Clinical diagnosis of alzheimer\u2019s disease: report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on alzheimer\u2019s disease. Neurology 34 (7), 939\u2013944 (1984).","journal-title":"Neurology"},{"issue":"3","key":"39465_CR37","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1212\/WNL.0b013e3181cb3e25","volume":"74","author":"RC Petersen","year":"2010","unstructured":"Petersen, R. C. et al. Alzheimer\u2019s disease neuroimaging initiative (ADNI): clinical characterization. Neurology 74 (3), 201\u2013209 (2010).","journal-title":"Neurology"},{"issue":"4","key":"39465_CR38","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1007\/s11682-012-9186-z","volume":"6","author":"PK Crane","year":"2012","unstructured":"Crane, P. K. et al. Development and assessment of a composite score for memory in the alzheimer\u2019s disease neuroimaging initiative (ADNI). Brain Imaging Behav. 6 (4), 502\u2013516 (2012).","journal-title":"Brain Imaging Behav."},{"issue":"4","key":"39465_CR39","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s11682-012-9176-1","volume":"6","author":"LE Gibbons","year":"2012","unstructured":"Gibbons, L. E. et al. A composite score for executive functioning, validated in alzheimer\u2019s disease neuroimaging initiative (ADNI) participants with baseline mild cognitive impairment. Brain Imaging Behav. 6 (4), 517\u2013527 (2012).","journal-title":"Brain Imaging Behav."},{"key":"39465_CR40","doi-asserted-by":"crossref","unstructured":"Folstein, M. F., Folstein, S. E. & McHugh, P. R. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12 (3), 189\u2009\u2013\u2009198 (1975).","DOI":"10.1016\/0022-3956(75)90026-6"},{"issue":"11","key":"39465_CR41","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1176\/ajp.141.11.1356","volume":"141","author":"WG Rosen","year":"1984","unstructured":"Rosen, W. G., Mohs, R. C. & Davis, K. L. A new rating scale for alzheimer\u2019s disease. Am. J. Psychiatry. 141 (11), 1356\u20131364 (1984).","journal-title":"Am. J. Psychiatry"},{"key":"39465_CR42","unstructured":"Wechsler, D. WMS-R: Wechsler Memory Scale\u2013Revised: Manual (Psychological Corporation, 1987)."},{"key":"39465_CR43","unstructured":"Rey, A. L\u2019examen Clinique en Psychologie (Presses universitaires de France, 1964)."},{"key":"39465_CR44","unstructured":"Wechsler, D. WAIS-R Manual: Wechsler Adult Intelligence Scale - Revised (Psychological Corp., 1981)."},{"key":"39465_CR45","unstructured":"Reitan, R. M. & Wolfson, D. The Halstead-Reitan neuropsychological test battery: theory and cinical interpretation. Neuropsychology (1985)."},{"key":"39465_CR46","doi-asserted-by":"crossref","unstructured":"Carone, D. & Sherman, O. S. A Compendium of neuropsychological tests: administration, norms, and commentary. Appl. Neuropsychol. 14, 62\u201363 (2007).","DOI":"10.1080\/09084280701280502"},{"key":"39465_CR47","doi-asserted-by":"crossref","unstructured":"French, T. M. Primary mental abilities. Psychoanal. Q. 8, 534\u2013555 (1938).","DOI":"10.1080\/21674086.1939.11925404"},{"key":"39465_CR48","doi-asserted-by":"crossref","unstructured":"Kaplan, E. A process approach to neuropsychological assessment. In Clinical Neuropsychology and Brain Function: Research, measurement, and Practice 127\u2013167 (American Psychological Association, 1988).","DOI":"10.1037\/10063-004"},{"issue":"1","key":"39465_CR49","doi-asserted-by":"publisher","first-page":"e12072","DOI":"10.1002\/trc2.12072","volume":"6","author":"SE Choi","year":"2020","unstructured":"Choi, S. E. et al. Development and validation of Language and visuospatial composite scores in ADNI. Alzheimers Dement. (N Y). 6 (1), e12072 (2020).","journal-title":"Alzheimers Dement. (N Y)"},{"key":"39465_CR50","doi-asserted-by":"crossref","unstructured":"Roth, C. R. & Helm-Estabrooks, N. Boston naming test. In Encyclopedia of Clinical Neuropsychology (eds. Kreutzer, J. S. et al.) 611\u2013615 (Springer International Publishing, 2018).","DOI":"10.1007\/978-3-319-57111-9_869"},{"issue":"4","key":"39465_CR51","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/j.1532-5415.2005.53221.x","volume":"53","author":"ZS Nasreddine","year":"2005","unstructured":"Nasreddine, Z. S. et al. The Montreal cognitive assessment, moca: a brief screening tool for mild cognitive impairment. J. Am. Geriatr. Soc. 53 (4), 695\u2013699 (2005).","journal-title":"J. Am. Geriatr. Soc."},{"issue":"2","key":"39465_CR52","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.neuroimage.2009.12.059","volume":"50","author":"KK Leung","year":"2010","unstructured":"Leung, K. K. et al. Robust atrophy rate measurement in alzheimer\u2019s disease using multi-site serial MRI: tissue-specific intensity normalization and parameter selection. Neuroimage 50 (2), 516\u2013523 (2010).","journal-title":"Neuroimage"},{"issue":"4","key":"39465_CR53","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1016\/j.neuroimage.2010.03.018","volume":"51","author":"KK Leung","year":"2010","unstructured":"Leung, K. K. et al. Automated cross-sectional and longitudinal hippocampal volume measurement in mild cognitive impairment and alzheimer\u2019s disease. Neuroimage 51 (4), 1345\u20131359 (2010).","journal-title":"Neuroimage"},{"issue":"1","key":"39465_CR54","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0169-2607(97)01803-8","volume":"53","author":"PA Freeborough","year":"1997","unstructured":"Freeborough, P. A., Fox, N. C. & Kitney, R. I. Interactive algorithms for the segmentation and quantitation of 3-D MRI brain scans. Comput. Methods Programs Biomed. 53 (1), 15\u201325 (1997).","journal-title":"Comput. Methods Programs Biomed."},{"issue":"1","key":"39465_CR55","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1097\/00004728-199801000-00027","volume":"22","author":"RP Woods","year":"1998","unstructured":"Woods, R. P. et al. Automated image registration: I. General methods and intrasubject, intramodality validation. J. Comput. Assist. Tomogr. 22 (1), 139\u2013152 (1998).","journal-title":"J. Comput. Assist. Tomogr"},{"issue":"1","key":"39465_CR56","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.neuroimage.2004.04.030","volume":"23","author":"EB Lewis","year":"2004","unstructured":"Lewis, E. B. & Fox, N. C. Correction of differential intensity inhomogeneity in longitudinal MR images. Neuroimage 23 (1), 75\u201383 (2004).","journal-title":"Neuroimage"},{"issue":"2","key":"39465_CR57","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/s12021-017-9326-0","volume":"15","author":"EN Manning","year":"2017","unstructured":"Manning, E. N. et al. A comparison of accelerated and Non-accelerated MRI scans for brain volume and boundary shift integral measures of volume change: evidence from the ADNI dataset. Neuroinformatics 15 (2), 215\u2013226 (2017).","journal-title":"Neuroinformatics"},{"issue":"2","key":"39465_CR58","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1097\/WAD.0b013e318260a79a","volume":"27","author":"KE Macdonald","year":"2013","unstructured":"Macdonald, K. E. et al. The value of hippocampal and temporal Horn volumes and rates of change in predicting future conversion to AD. Alzheimer Dis. Assoc. Disord. 27 (2), 168\u2013173 (2013).","journal-title":"Alzheimer Dis. Assoc. Disord."},{"issue":"1","key":"39465_CR59","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/WAD.0b013e3182163b62","volume":"26","author":"LG Apostolova","year":"2012","unstructured":"Apostolova, L. G. et al. Hippocampal atrophy and ventricular enlargement in normal aging, mild cognitive impairment (MCI), and alzheimer disease. Alzheimer Dis. Assoc. Disord. 26 (1), 17\u201327 (2012).","journal-title":"Alzheimer Dis. Assoc. Disord."},{"issue":"3","key":"39465_CR60","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.neuroimage.2006.05.048","volume":"32","author":"L Ferrarini","year":"2006","unstructured":"Ferrarini, L. et al. Shape differences of the brain ventricles in alzheimer\u2019s disease. Neuroimage 32 (3), 1060\u20131069 (2006).","journal-title":"Neuroimage"},{"issue":"2","key":"39465_CR61","doi-asserted-by":"publisher","first-page":"95","DOI":"10.12779\/dnd.2024.23.2.95","volume":"23","author":"JS Lee","year":"2024","unstructured":"Lee, J. S., Heo, D. Y., Choi, K. H. & Kim, H. J. Impact of the ventricle size on alzheimer\u2019s disease progression: a retrospective longitudinal study. Dement. Neurocogn. Disord. 23 (2), 95\u2013106 (2024).","journal-title":"Dement. Neurocogn. Disord."},{"issue":"Pt 9","key":"39465_CR62","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1093\/brain\/awn146","volume":"131","author":"SM Nestor","year":"2008","unstructured":"Nestor, S. M. et al. Ventricular enlargement as a possible measure of alzheimer\u2019s disease progression validated using the alzheimer\u2019s disease neuroimaging initiative database. Brain 131 (Pt 9), 2443\u20132454 (2008).","journal-title":"Brain"},{"key":"39465_CR63","doi-asserted-by":"publisher","first-page":"665803","DOI":"10.3389\/fnana.2021.665803","volume":"15","author":"J Kaur","year":"2021","unstructured":"Kaur, J. et al. Waste clearance in the brain. Front. Neuroanat. 15, 665803 (2021).","journal-title":"Front. Neuroanat."},{"issue":"1","key":"39465_CR64","doi-asserted-by":"publisher","first-page":"11480","DOI":"10.1038\/s41598-019-44938-1","volume":"9","author":"KN Magdoom","year":"2019","unstructured":"Magdoom, K. N. et al. MRI of whole rat brain perivascular network reveals role for ventricles in brain waste clearance. Sci. Rep. 9 (1), 11480 (2019).","journal-title":"Sci. Rep."},{"issue":"1","key":"39465_CR65","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13195-024-01612-7","volume":"17","author":"N Cullell","year":"2025","unstructured":"Cullell, N. et al. Glymphatic system clearance and alzheimer\u2019s disease risk: a CSF proteome-wide study. Alzheimers Res. Ther. 17 (1), 31 (2025).","journal-title":"Alzheimers Res. Ther."},{"issue":"2","key":"39465_CR66","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3233\/JAD-150306","volume":"49","author":"JP Coutu","year":"2016","unstructured":"Coutu, J. P., Goldblatt, A., Rosas, H. D. & Salat, D. H. White matter changes are associated with ventricular expansion in aging, mild cognitive Impairment, and alzheimer\u2019s disease. J. Alzheimers Dis. 49 (2), 329\u2013342 (2016).","journal-title":"J. Alzheimers Dis."},{"issue":"21","key":"39465_CR67","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1212\/WNL.0b013e3181a71236","volume":"72","author":"DS Knopman","year":"2009","unstructured":"Knopman, D. S. et al. Brain and ventricular volumetric changes in frontotemporal Lobar degeneration over 1 year. Neurology 72 (21), 1843\u20131849 (2009).","journal-title":"Neurology"},{"issue":"4","key":"39465_CR68","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s00415-008-0750-9","volume":"255","author":"BH Ridha","year":"2008","unstructured":"Ridha, B. H. et al. Volumetric MRI and cognitive measures in alzheimer disease: comparison of markers of progression. J. Neurol. 255 (4), 567\u2013574 (2008).","journal-title":"J. Neurol."},{"issue":"6","key":"39465_CR69","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1002\/jmri.1880070620","volume":"7","author":"NC Fox","year":"1997","unstructured":"Fox, N. C. & Freeborough, P. A. Brain atrophy progression measured from registered serial MRI: validation and application to alzheimer\u2019s disease. J. Magn. Reson. Imaging 7 (6), 1069\u20131075 (1997).","journal-title":"J. Magn. Reson. Imaging"},{"issue":"4","key":"39465_CR70","first-page":"196","volume":"18","author":"F Ezekiel","year":"2004","unstructured":"Ezekiel, F. et al. Comparisons between global and focal brain atrophy rates in normal aging and alzheimer disease: boundary shift integral versus tracing of the entorhinal cortex and hippocampus. Alzheimer Dis. Assoc. Disord. 18 (4), 196\u2013201 (2004).","journal-title":"Alzheimer Dis. Assoc. Disord"},{"issue":"Pt 2","key":"39465_CR71","first-page":"125","volume":"13","author":"KK Leung","year":"2010","unstructured":"Leung, K. K. et al. Increasing power to predict mild cognitive impairment conversion to alzheimer\u2019s disease using hippocampal atrophy rate and statistical shape models. Med. Image Comput. Comput. Assist. Interv. 13 (Pt 2), 125\u2013132 (2010).","journal-title":"Med. Image Comput. Comput. Assist. Interv."},{"issue":"3","key":"39465_CR72","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1212\/01.WNL.0000106462.72282.90","volume":"62","author":"AT Du","year":"2004","unstructured":"Du, A. T. et al. Higher atrophy rate of entorhinal cortex than hippocampus in AD. Neurology 62 (3), 422\u2013427 (2004).","journal-title":"Neurology"},{"issue":"11","key":"39465_CR73","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1002\/hipo.20573","volume":"19","author":"F Shi","year":"2009","unstructured":"Shi, F. et al. Hippocampal volume and asymmetry in mild cognitive impairment and alzheimer\u2019s disease: Meta-analyses of MRI studies. Hippocampus 19 (11), 1055\u20131064 (2009).","journal-title":"Hippocampus"},{"issue":"4","key":"39465_CR74","doi-asserted-by":"publisher","first-page":"328","DOI":"10.3390\/anatomia2040029","volume":"2","author":"F Kurth","year":"2023","unstructured":"Kurth, F. & Luders, E. Hippocampal asymmetry increases with age. Anatomia 2 (4), 328\u2013335 (2023).","journal-title":"Anatomia"},{"issue":"Pt B","key":"39465_CR75","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.neuropsychologia.2016.08.016","volume":"93","author":"A Ezzati","year":"2016","unstructured":"Ezzati, A. et al. Differential association of left and right hippocampal volumes with verbal episodic and spatial memory in older adults. Neuropsychologia 93 (Pt B), 380\u2013385 (2016).","journal-title":"Neuropsychologia"},{"key":"39465_CR76","doi-asserted-by":"crossref","unstructured":"Hurley, R. S. et al. Hemispheric asymmetries in hippocampal volume related to memory in left and right Temporal variants of frontotemporal degeneration. Front. Neurol. 15, 2563 (2024).","DOI":"10.3389\/fneur.2024.1374827"},{"issue":"1","key":"39465_CR77","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.neuroimage.2006.06.035","volume":"33","author":"C Piekema","year":"2006","unstructured":"Piekema, C. et al. The right hippocampus participates in short-term memory maintenance of object\u2013location associations. NeuroImage 33 (1), 374\u2013382 (2006).","journal-title":"NeuroImage"},{"issue":"7","key":"39465_CR78","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1093\/geronb\/gbz120","volume":"75","author":"M Caillaud","year":"2020","unstructured":"Caillaud, M. et al. Evidence of a relation between hippocampal volume, white matter hyperintensities, and cognition in subjective cognitive decline and mild cognitive impairment. J. Gerontol. B Psychol. Sci. Soc. Sci. 75 (7), 1382\u20131392 (2020).","journal-title":"J. Gerontol. B Psychol. Sci. Soc. Sci."},{"key":"39465_CR79","doi-asserted-by":"crossref","unstructured":"Peng, G. P. et al. Correlation of hippocampal volume and cognitive performances in patients with either mild cognitive impairment or alzheimer\u2019s disease. CNS Neurosci. Therapeut. 21, 15\u201322 (2015).","DOI":"10.1111\/cns.12317"},{"issue":"1","key":"39465_CR80","doi-asserted-by":"publisher","first-page":"e12226","DOI":"10.1002\/trc2.12226","volume":"7","author":"CJ Weber","year":"2021","unstructured":"Weber, C. J. et al. The worldwide alzheimer\u2019s disease neuroimaging initiative: ADNI-3 updates and global perspectives. Alzheimers Dement. (N Y). 7 (1), e12226 (2021).","journal-title":"Alzheimers Dement. (N Y)"},{"key":"39465_CR81","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.nicl.2018.04.016","volume":"19","author":"C Falcon","year":"2018","unstructured":"Falcon, C. et al. Longitudinal structural cerebral changes related to core CSF biomarkers in preclinical alzheimer\u2019s disease: a study of two independent datasets. Neuroimage Clin. 19, 190\u2013201 (2018).","journal-title":"Neuroimage Clin."},{"issue":"1","key":"39465_CR82","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13195-024-01450-7","volume":"16","author":"M Fujishima","year":"2024","unstructured":"Fujishima, M., Kawasaki, Y., Mitsuhashi, T. & Matsuda, H. Impact of amyloid and Tau positivity on longitudinal brain atrophy in cognitively normal individuals. Alzheimers Res. Ther. 16 (1), 77 (2024).","journal-title":"Alzheimers Res. Ther."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39465-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39465-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39465-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:25:50Z","timestamp":1781641550000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-39465-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":82,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["39465"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-39465-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"1 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The institutional review boards of all participating centers approved the study procedure and all participants or their authorized representatives provided written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}}],"article-number":"14092"}}