{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:50:47Z","timestamp":1791395447962,"version":"4.3.3"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":56,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24dk0207068"],"award-info":[{"award-number":["JP24dk0207068"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP25dk0207075"],"award-info":[{"award-number":["JP25dk0207075"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP26dk0207078"],"award-info":[{"award-number":["JP26dk0207078"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24K10653"],"award-info":[{"award-number":["JP24K10653"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25K19014"],"award-info":[{"award-number":["JP25K19014"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alz &amp;amp; Dem Diag Ass &amp;amp; Dis Mo"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>In clinical practice, patients with Alzheimer's disease (AD) often present with cognitive and functional profiles that diverge from what is expected. We tested whether the Mini\u2010Mental State Examination Clinical Dementia Rating Sum of Boxes (MMSE\u2013CDR\u2010SB) residual, defined as observed minus expected CDR\u2010SB from a published MMSE\u2013CDR\u2010SB reference equation, reflects clinically meaningful deviation from the expected cognitive\u2013functional relationship.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Using National Alzheimer's Coordinating Center data, we analyzed an autopsy cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a01981) and a separate clinical diagnosis cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a03184). Negative residual values indicated less functional impairment than expected for a given cognitive score, and positive values indicated greater functional impairment than expected.\u00a0Associations were examined using multivariable logistic regression adjusted for MMSE score range, age, sex, and education.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Lower residual values were associated with lower odds of amyloid and AD\u2010type tau pathology. Higher residual values showed a directional association with transactive response DNA binding protein 43 kDa; vascular burden was also associated with the residual index but across a broader range. In the clinical cohort, higher residual values were enriched in progressive supranuclear palsy and frontotemporal lobar degeneration (other), whereas AD cases clustered near the reference pattern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>The MMSE\u2013CDR\u2010SB residual may help flag less AD\u2010typical presentations for further etiologic evaluation, but cannot be interpreted as a pathology\u2010specific marker due to substantial overlap across diagnostic groups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/dad2.70460","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:34:43Z","timestamp":1787744083000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MMSE\u2013CDR\u2010SB residual as an exploratory indicator of deviation from an Alzheimer's disease\u2013typical cognitive\u2013functional pattern"],"prefix":"10.1002","volume":"18","author":[{"given":"Ambre","family":"Mouni\u00e9","sequence":"first","affiliation":[{"name":"Dementia Inclusion and Therapeutics The University of Tokyo Hospital  Tokyo Japan"},{"name":"Cognitive Sciences Universit\u00e9 C\u00f4te d'Azur  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4351-9526","authenticated-orcid":false,"given":"Kenichiro","family":"Sato","sequence":"additional","affiliation":[{"name":"Dementia Inclusion and Therapeutics The University of Tokyo Hospital  Tokyo Japan"},{"name":"Unit for Early and Exploratory Clinical Development The University of Tokyo Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Dementia Inclusion and Therapeutics The University of Tokyo Hospital  Tokyo Japan"},{"name":"Unit for Early and Exploratory Clinical Development The University of Tokyo Hospital  Tokyo Japan"},{"name":"Department of Neurology The University of Tokyo Hospital  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Department of Neurology Tokyo Metropolitan Institute of Geriatrics and Gerontology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Ihara","sequence":"additional","affiliation":[{"name":"Department of Neurology Tokyo Metropolitan Institute of Geriatrics and Gerontology  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiki","family":"Niimi","sequence":"additional","affiliation":[{"name":"Dementia Inclusion and Therapeutics The University of Tokyo Hospital  Tokyo Japan"},{"name":"Unit for Early and Exploratory Clinical Development The University of Tokyo Hospital  Tokyo 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