@article{2bc40dd3812849eb8dbef6f5f093ab45,
title = "Specific Association of Worry With Amyloid-β But Not Tau in Cognitively Unimpaired Older Adults",
abstract = "Objective: Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established. Methods: Baseline data from the A4 and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies were analyzed. Older adult participants (n = 4,486) underwent assessments of anxiety (State-Trait Anxiety Inventory–6 item version [STAI]), and cerebral amyloid-beta (Aβ; 18F-florbetapir) PET and a subset underwent tau ( 18F-flortaucipir) PET. Linear regressions estimated associations of Aβ in a cortical composite and tau in the amygdala, entorhinal, and inferior temporal regions with STAI-Total and individual STAI item scores. Models adjusted for age, sex, education, marital status, depression, Apolipoprotein ε4 genotype, and subjective and objective cognition (Cognitive Function Index-participant; Preclinical Alzheimer Cognitive Composite). Results: Greater Aβ deposition was significantly associated with higher STAI-Worry, adjusting for all covariates, but not with other STAI items or STAI-Total scores. In mediation analyses, the association of Aβ with STAI-Worry was partially mediated by subjective cognition with a stronger direct effect. No associations were found for regional tau deposition with STAI-Total or STAI-Worry score. Conclusion: Greater worry was associated with Aβ but not tau deposition, independent of subjective and objective cognition in cognitively unimpaired (CU) older adults. These findings implicate worry as an early, specific behavioral marker and a possible therapeutic target in preclinical AD.",
keywords = "amyloid-{\ss}, Anxiety, preclinical Alzheimer's disease, tau, worry",
author = "Soyoung Lee and Zide, {Benjamin S.} and Palm, {Stephan T.} and Drew, {William J.} and Sperling, {Reisa A.} and Jacobs, {Heidi I.L.} and Siddiqi, {Shan H.} and Donovan, {Nancy J.}",
note = "Funding Information: This study was supported by philanthropic gifts (the Neuropsychiatry of Aging Research Fund and the Geriatric Psychiatry Fund) to the Division of Geriatric Psychiatry, Brigham and Women's Hospital . Funding Information: The A4 Study is a secondary prevention trial in preclinical Alzheimer's disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public-private-philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging, Eli Lilly and Company, Alzheimer's Association, Accelerating Medicines Partnership, GHR Foundation, an anonymous foundation and additional private donors, with in-kind support from Avid and Cogstate. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer's Association and GHR Foundation. The A4 and LEARN Studies are led by Dr. Reisa Sperling at Brigham and Women's Hospital, Harvard Medical School and Dr. Paul Aisen at the Alzheimer's Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data in order to advance the quest to find a successful treatment for Alzheimer's disease. We would like to acknowledge the dedication of all the participants, the site personnel, and all of the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available on: a4study.org/a4-study-team. Publisher Copyright: {\textcopyright} 2024 American Association for Geriatric Psychiatry",
year = "2024",
month = oct,
doi = "10.1016/j.jagp.2024.04.016",
language = "English",
volume = "32",
pages = "1203--1214",
journal = "American Journal of Geriatric Psychiatry",
issn = "1064-7481",
publisher = "Elsevier B.V.",
number = "10",
}