Association of plasma biomarkers of Alzheimer's disease and related disorders with cognition and cognitive decline: The MYHAT population‐based study

Author:

Zhang Yingjin1,Ferreira Pamela C. L.2,Jacobsen Erin2,Bellaver Bruna2,Pascoal Tharick A.23,Snitz Beth E.3,Chang Chung‐Chou H.14,Villemagne Victor L.2,Ganguli Mary235,Karikari Thomas K.2ORCID

Affiliation:

1. Department of Biostatistics  School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA

2. Department of Psychiatry School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA

3. Department of Neurology School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA

4. Department of Medicine School of Medicine University of Pittsburgh Pittsburgh Pennsylvania USA

5. Department of Epidemiology  School of Public Health University of Pittsburgh Pittsburgh Pennsylvania USA

Abstract

AbstractINTRODUCTIONPlasma biomarkers of Alzheimer's disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains.METHODSIn a prospective study with repeated assessments of a randomly selected population‐based cohort (n = 787, median age 73), we evaluated performance and decline in different cognitive domains over up to 8 years in relation to plasma concentrations of amyloid beta 42/40 (Aβ42/40) ratio, phosphorylated tau181 (p‐tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).RESULTSCross‐sectionally, memory showed the strongest associations with p‐tau181, and attention, executive, and visuospatial functions with NfL. Longitudinally, memory decline was distinguishable with all biomarker profiles dichotomized according to data‐driven cutoffs, most efficiently with Aβ42/40. GFAP and Aβ42/40 were the best discriminators of decline patterns in language and visuospatial functions, respectively.DISCUSSIONThese relatively non‐invasive tests may be beneficial for clinical screening after replication in other populations and validation through neuroimaging or cerebrospinal fluid analysis.Highlights We performed a prospective study with up to 8 years of repeated domain‐specific cognitive assessments and baseline plasma Alzheimer's disease and related dementias biomarker measurements in a randomly selected population‐based cohort. We considered distinct growth curves of trajectories of different cognitive domains and survival bias induced by missing data by adding quadratic time and applying joint modeling technique. Cross‐sectionally, memory showed the strongest associations with plasma phosphorylated tau181, while attention, executive, and visuospatial functions were most strongly associated with neurofilament light chain. Longitudinally, memory and visuospatial declines were most efficiently distinguished by dichotomized amyloid beta 42/40 profile among all plasma biomarkers, while language was by dichotomized glial fibrillary acidic protein. These relatively non‐invasive tests may be beneficial for clinical screening; however, they will need replication in other populations and validation through neuroimaging and/or cerebrospinal fluid assessments.

Funder

Alzheimer's Association

National Institutes of Health

Publisher

Wiley

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