Cognitive trajectory in mild cognitive impairment due to primary age-related tauopathy

Author:

Teylan Merilee1,Mock Charles1,Gauthreaux Kathryn1,Chen Yen-Chi1ORCID,Chan Kwun C G1,Hassenstab Jason23,Besser Lilah M4,Kukull Walter A1,Crary John F5

Affiliation:

1. National Alzheimer’s Coordinating Center, Department of Epidemiology, University of Washington, Seattle, WA, USA

2. Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

3. Department of Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA

4. School of Urban and Regional Planning, Florida Atlantic University, Boca Raton, FL, USA

5. Neuropathology Brain Bank and Research CoRE, Department of Pathology, Nash Family Department of Neuroscience, Friedman Brain Institute, Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Abstract

Abstract Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer’s disease. 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’s 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’s 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’s 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’s disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR® 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 ε4 (APOE ε4) 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’s disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer’s 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’s 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’s disease.

Funder

NIA

National Institutes of Health

Alzheimer's Association

Tau Consortium

NACC

NIH

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

Reference25 articles.

1. The National Alzheimer's Coordinating Center (NACC) database: the uniform data set;Beekly;Alzheimer Dis Assoc Disord,2007

2. The National Alzheimer's Coordinating Center (NACC) Database: an Alzheimer disease database;Beekly;Alzheimer Dis Assoc Disord,2004

3. Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer's disease;Bell;Alzheimers Dement,2019

4. Comparison of symptomatic and asymptomatic persons with primary age-related tauopathy;Besser;Neurology,2017

5. The Revised National Alzheimer's Coordinating Center's Neuropathology Form-available data and new analyses;Besser;J Neuropathol Exp Neurol,2018

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3