Search

Introduction: We examine whether the association between key plasma biomarkers (amyloid β [aβ] 42/40, total tau (t-tau), neurofilament light [NfL]) and cognitive trajectories (executive function [EF] and episodic memory [EM]) is mediated through neurodegeneration., Methods: All participants were recruited from the University of California, Davis-Alzheimer's Disease Research Center ( n  = 473; baseline age range = 49-95 years, 60% women). We applied an accelerated longitudinal design to test latent growth models for EF and EM, and path and mediation analyses. Age was centered at 75 years, and all models were adjusted for sex, education, and ethnicity., Results: HV differentially mediated the association aβ 42/40 and NfL on EF and EM level and change. Hippocampal volume (HV) did not mediate the association between t-tau and cognitive performance., Discussion: Neurodegeneration as represented with HV selectively mediates the association between key non-invasive plasma biomarkers and cognitive trajectories in an ethnoracially and clinically diverse community-based sample., Competing Interests: All authors report no disclosures relevant to the manuscript. Author disclosures are available in the supporting information., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Introduction: Composite scores based on psychometrically rigorous cognitive assessments are well suited for early diagnosis and disease monitoring., Methods: We developed and cross-validated the Brain Health Assessment-Cognitive Score (BHA-CS), based on a brief computerized battery, in 451 cognitively normal (CN) and 399 cognitively impaired (mild cognitive impairment [MCI] or dementia) older adults. We investigated its long-term reliability and reliable change indices at longitudinal follow-up (N = 340), and the association with amyloid beta (Aβ) burden in the CN subgroup with Aβ positron emission tomography (N = 119)., Results: The BHA-CS was accurate at detecting cognitive impairment and exhibited excellent long-term stability. Reliable decline over one year was detected in 75% of participants with dementia, 44% with MCI, and 3% of CN. Among CN, the Aβ-positive group showed worse longitudinal performance on the BHA-CS compared to the Aβ-negative group., Discussion: The BHA-CS is sensitive to cognitive decline in preclinical and prodromal neurodegenerative disease., Competing Interests: No authors reported competing interests relevant to this study. Dr. La Joie has received research funding from the Alzheimer's Association. Dr. Rabinovici has received consulting fees or speaking honoraria from GE Healthcare, Axon Neurosciences, Merck, Eisai, Roche, and Genentech; grants from Avid Radiopharmaceuticals, Eli Lilly and Company, GE Healthcare, Life Molecular Imaging; and research funding from the National Institutes of Health (NIH), the Rainwater Charitable Foundation, and the Alzheimer's Association. Dr. Miller has received research funding from the NIH; serves as Medical Director for the John Douglas French Foundation; Scientific Director for the Tau Consortium; Director/Medical Advisory Board of the Larry L. Hillblom Foundation; Scientific Advisory Board Member for the National Institute for Health Research Cambridge Biomedical Research Centre and its subunit, the Biomedical Research Unit in Dementia (UK); and Board Member for the American Brain Foundation (ABF). Dr. Tomaszewski Farias has received research funding from the NIH. Dr. Kramer has received research funding from the NIH and the Larry L. Hillblom Foundation and royalties from Pearson Education, Inc. Dr. Rankin has received research funding from the NIH, Quest Diagnostics, the Rainwater Charitable Foundation, the Weill Family Foundation, and the Marcus Foundation. Dr. Possin has received research funding from the NIH, Quest Diagnostics, the Global Brain Health Institute, the Merck Foundation, and the Rainwater Charitable Foundation. No other disclosures were reported., (© 2020 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, Inc. on behalf of the Alzheimer's Association.)