{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T03:54:31Z","timestamp":1785902071036,"version":"3.56.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,14]],"date-time":"2020-03-14T00:00:00Z","timestamp":1584144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To characterize trajectories of normative cognitive aging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Older persons without dementia at study enrollment (n = 1,010) had annual cognitive testing for up to 24\u2009years (mean = 9.9\u2009years, standard deviation = 5.0), died, and underwent a neuropathologic examination to quantify 9 postmortem markers of common neurodegenerative and cerebrovascular conditions. To accommodate the heterogeneity in cognitive trajectories, we used functional mixed effects models, which allow individuals to have different patterns of cognitive decline under a unified model structure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a functional mixed effects model, postmortem markers (Alzheimer disease pathology, Lewy bodies, transactive response DNA\u2010binding protein 43 pathology, hippocampal sclerosis, atherosclerosis, gross infarcts) were associated with global cognitive decline. Residual global cognitive decline after adjustment for neuropathologic burden was weakly related to age at death; it occurred in only about one\u2010third of participants, mostly proximate to death. Results were comparable after eliminating the initial cognitive assessments to minimize retest learning or controlling for frailty proximate to death. Analyses were also conducted with composite measures of episodic memory and perceptual speed. Residual decline not attributable to neuropathologic burden was confined to a subset for each outcome and was most evident proximate to death. Age at death was unrelated to residual decline in episodic memory but was related to residual decline in perceptual speed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Late life cognitive loss mainly reflects non\u2010normative pathologic and mortality\u2010related processes rather than normative age\u2010related processes. <jats:bold>ANN NEUROL 2020;87:816\u2013829<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25711","type":"journal-article","created":{"date-parts":[[2020,3,7]],"date-time":"2020-03-07T02:14:11Z","timestamp":1583547251000},"page":"816-829","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Normative Cognitive Decline in Old Age"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9592-0333","authenticated-orcid":false,"given":"Robert S.","family":"Wilson","sequence":"first","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago IL"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago IL"},{"name":"Department of Psychiatry and Behavioral Sciences  Rush University Medical Center, Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago IL"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-8758","authenticated-orcid":false,"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago IL"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago IL"},{"name":"Department of Neurological Sciences Rush University Medical Center  Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Boyle","sequence":"additional","affiliation":[{"name":"Rush Alzheimer's Disease Center Rush University Medical Center  Chicago IL"},{"name":"Department of Psychiatry and Behavioral Sciences  Rush University Medical Center, Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,14]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"569","volume-title":"Handbook of child psychology. 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