{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T09:41:11Z","timestamp":1792316471331,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["BCA527734"],"award-info":[{"award-number":["BCA527734"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["agsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J American Geriatrics Society"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Functional impairment (FI) is a key criterion for diagnosing dementia. However, subtle functional changes may occur during preclinical and prodromal phases but may not be accurately characterized. Furthermore, research linking FI to Alzheimer disease (AD) biofluid biomarkers is limited. Here we examined cross\u2010sectional associations between cerebrospinal fluid (CSF) AD biomarkers and persistent versus transient FI in dementia\u2010free older adults, and the longitudinal association of FI with incident dementia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from 1000 participants (age 72.9\u2009\u00b1\u20097.0; 45.2% female; 62.8% MCI) from the Alzheimer's Disease Neuroimaging Initiative were analyzed. CSF biomarkers included p\u2010tau181, A\u03b242, and ptau\u2010181\/A\u03b242 ratio. Three Functional Activities Questionnaire items of \u201cpreparing a hot beverage,\u201d \u201cpreparing a balanced meal,\u201d and \u201cshopping alone\u201d were identified by factor analysis as assessing function rather than cognition directly. Persistent\u2010FI was operationalized as FI present at&gt;\u2009two\u2010thirds of pre\u2010dementia visits. Comparator groups included Transient\u2010FI and No\u2010FI. Linear regression modeled the association between FI status and baseline biomarker levels, while Cox regression assessed the association between FI and incident dementia. Models adjusted for age, sex, education, APOE\u2010\u03b54 status, and MMSE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared to No\u2010FI, Persistent\u2010FI was associated with lower A\u03b242 (Beta\u2009=\u2009\u22128.93; 95% CI: \u221213.56 to \u22124.03;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), higher p\u2010tau181 (Beta\u2009=\u200910.81; 95% CI: 0.44\u201322.26;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.041), and ptau181\/A\u03b242 ratio (Beta\u2009=\u200921.66; 95% CI: 7.02\u201338.31;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). In contrast, Transient\u2010FI showed no significant associations. APOE\u2010\u03b54 carrier status was more prevalent in the Persistent\u2010FI group compared to No\u2010FI (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009), but not in Transient\u2010FI (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.931). Compared to No\u2010FI, Persistent\u2010FI had a 6.66\u2010fold greater dementia incidence rate (95% CI: 4.98\u20138.91,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), while Transient\u2010FI had a 1.72\u2010fold greater incidence rate (95% CI: 1.09\u20132.72,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.021).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Findings extend the limited research on the association of FI with CSF AD biomarkers in dementia\u2010free populations. Operationalizing FI\u2010related risk by persistence enhances prognostication, identifying individuals with greater AD pathology and progression risk. This approach could enhance screening, early detection, and risk stratification, informing timely interventions before dementia onset.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgs.70247","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T05:00:30Z","timestamp":1765861230000},"page":"447-457","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Persistent Functional Impairment as an Early Indicator of Alzheimer Disease Pathology and Progression"],"prefix":"10.1111","volume":"74","author":[{"given":"Maryam","family":"Ghahremani","sequence":"first","affiliation":[{"name":"Psychiatry, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Hotchkiss Brain Institute, Cumming School of Medicine University of Calgary  Calgary Alberta 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Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Community Health Sciences, Cumming School of Medicine University of Calgary  Calgary Alberta Canada"},{"name":"Pathology and Laboratory Medicine, Cumming School of Medicine University of Calgary  Calgary Alberta 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