{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T22:49:46Z","timestamp":1784155786711,"version":"3.55.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health\u2019s"},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"crossref","award":["R01AG062706"],"award-info":[{"award-number":["R01AG062706"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Brain atrophy is associated with degenerative neuropathologies and the clinical status of dementia. Whether dementia is associated with atrophy independent of neuropathologies is not known. In this study, we examined the pattern of atrophy associated with dementia while accounting for the most common dementia-related neuropathologies. We used data from National Alzheimer\u2019s Coordinating Center (n = 129) and Alzheimer\u2019s Disease Neuroimaging Initiative (n = 47) participants with suitable in vivo 3D-T1w MRI and autopsy data. We determined dementia status at the visit closest to MRI. We examined the following dichotomized neuropathological variables: Alzheimer\u2019s disease neuropathology, hippocampal sclerosis, Lewy bodies, cerebral amyloid angiopathy and atherosclerosis. Voxel-based morphometry identified areas associated with dementia after accounting for neuropathologies. Identified regions of interest were further analysed. We used multiple linear regression models adjusted for neuropathologies and demographic variables. We also examined models with dementia and Clinical Dementia Rating sum of the boxes as the outcome and explored the potential mediating effect of medial temporal lobe structure volumes on the relationship between pathology and cognition. We found strong associations for dementia with volumes of the hippocampus, amygdala and parahippocampus (semi-partial correlations \u2265 0.28, P &amp;lt; 0.0001 for all regions in National Alzheimer\u2019s Coordinating Center; semi-partial correlations \u2265 0.35, P \u2264 0.01 for hippocampus and parahippocampus in Alzheimer\u2019s Disease Neuroimaging Initiative). Dementia status accounted for more unique variance in atrophy in these structures (\u223c8%) compared with neuropathological variables; the only exception was hippocampal sclerosis which accounted for more variance in hippocampal atrophy (10%). We also found that the volumes of the medial temporal lobe structures contributed towards explaining the variance in Clinical Dementia Rating sum of the boxes (ranging from 5% to 9%) independent of neuropathologies and partially mediated the association between Alzheimer\u2019s disease neuropathology and cognition. Even after accounting for the most common neuropathologies, dementia still had among the strongest associations with atrophy of medial temporal lobe structures. This suggests that atrophy of the medial temporal lobe is most related to the clinical status of dementia rather than Alzheimer's disease or other neuropathologies, with the potential exception of hippocampal sclerosis.<\/jats:p>","DOI":"10.1093\/braincomms\/fcac052","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T07:10:07Z","timestamp":1646377807000},"source":"Crossref","is-referenced-by-count":41,"title":["Dementia is associated with medial temporal atrophy even after accounting for neuropathologies"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6256-857X","authenticated-orcid":false,"given":"Davis C.","family":"Woodworth","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Sheikh-Bahaei","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiana A.","family":"Scambray","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Phelan","sequence":"additional","affiliation":[{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Perez-Rosendahl","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda M.","family":"Corrada","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA"},{"name":"Department of Epidemiology, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia H.","family":"Kawas","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA"},{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8960-2213","authenticated-orcid":false,"given":"Seyed Ahmad","family":"Sajjadi","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Alzheimer's Disease Neuroimaging Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"issue":"2","key":"2022032513000439600_fcac052-B1","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/mrm.1910080210","article-title":"Quantitative NMR measurements of hippocampal atrophy in Alzheimer's disease","volume":"8","author":"Seab","year":"1988","journal-title":"Magn Reson 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