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Both share the neuropathological features of tau aggregates and neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer\u2019s disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer\u2019s disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer\u2019s Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer\u2019s disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR\u00ae Dementia Staging Instrument and in five cognitive domains (episodic memory, attention\/working memory, executive function, language\/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein \u03b54 (APOE \u03b54) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer\u2019s disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer\u2019s disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer\u2019s disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.1093\/brain\/awz403","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T23:56:56Z","timestamp":1575676616000},"page":"611-621","source":"Crossref","is-referenced-by-count":65,"title":["Cognitive trajectory in mild cognitive impairment due to primary age-related tauopathy"],"prefix":"10.1093","volume":"143","author":[{"given":"Merilee","family":"Teylan","sequence":"first","affiliation":[{"name":"National Alzheimer\u2019s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Mock","sequence":"additional","affiliation":[{"name":"National Alzheimer\u2019s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Gauthreaux","sequence":"additional","affiliation":[{"name":"National Alzheimer\u2019s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-306X","authenticated-orcid":false,"given":"Yen-Chi","family":"Chen","sequence":"additional","affiliation":[{"name":"National Alzheimer\u2019s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwun C G","family":"Chan","sequence":"additional","affiliation":[{"name":"National Alzheimer\u2019s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Hassenstab","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA"},{"name":"Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilah M","family":"Besser","sequence":"additional","affiliation":[{"name":"School of Urban and Regional Planning, Florida Atlantic University, Boca Raton, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter A","family":"Kukull","sequence":"additional","affiliation":[{"name":"National Alzheimer\u2019s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F","family":"Crary","sequence":"additional","affiliation":[{"name":"Neuropathology Brain Bank and Research CoRE, Department of Pathology, Nash Family Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer\u2019s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,13]]},"reference":[{"key":"2020021011133363600_awz403-B1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1097\/WAD.0b013e318142774e","article-title":"The National Alzheimer's Coordinating Center (NACC) database: the uniform data set","volume":"21","author":"Beekly","year":"2007","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"2020021011133363600_awz403-B2","first-page":"270","article-title":"The National Alzheimer's Coordinating Center (NACC) Database: an Alzheimer disease database","volume":"18","author":"Beekly","year":"2004","journal-title":"Alzheimer Dis Assoc Disord"},{"key":"2020021011133363600_awz403-B3","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jalz.2018.07.215","article-title":"Neuropathologic, genetic, and longitudinal 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