Elevated temporal tau PET predicts faster cognitive decline in women than men: A meta‐analysis
Year: 2026
Type: article
Abstract: INTRODUCTION: Women show higher levels of Alzheimer's disease (AD) pathology than men, but the implications for cognitive decline remain unclear. Determining the extent to which tau burden differentially accelerates cognitive decline in men and women will provide critical insights into sex-specific pathways of disease progression. METHODS: We leveraged tau positron emission tomography (PET), amyloid beta (Aβ) PET, apolipoprotein E (APOE) ε4 genotyping, and longitudinal cognitive data over approximately 8.6 (standard deviation [SD] = 3.8) years from 1007 cognitively unimpaired adults across three cohorts. Cognitive trajectories were modeled with linear mixed-effects regression including sex × tau × time interactions, and results were synthesized using random-effects meta-analysis. RESULTS: Higher tau burden in medial and lateral temporal regions was associated with faster cognitive decline in women than in men. DISCUSSION: High tau burden carries a disproportionately greater cognitive cost for women, underscoring the need for sex-specific approaches to early detection and therapeutic intervention in AD. HIGHLIGHTS: A meta-analysis across three independent cohorts shows that female cognitive advantage at low tau shifts to vulnerability at higher tau. Sex differences in tau-related cognitive decline were consistent after accounting for amyloid burden. Sex-specific rates of cognitive decline should be considered in clinical trial design.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.71031
Authors: Annie Li, Hannah M. Klinger, Mabel Seto, Colin Birkenbihl, Michael J. Properzi, Michelle Farrell, Emma Thibault, Aaron P. Schultz, Diana L. Townsend, Madison Cuppels, Jane A. Brown, Kathryn V. Papp, Rebecca E. Amariglio, Hyun‐Sik Yang, Michael C. Donohue, Robert A. Rissman, Tobey J. Betthauser, Rebecca E. Langhough, Erin M. Jonaitis, Karly Cody, Sterling C. Johnson, Dorene M. Rentz, Keith A. Johnson, Reisa A. Sperling, Rachel F. Buckley, Gillian T. Coughlan, the A4 Study Team
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,200
Awards: G1557667123, G2080581370, G2342946399, G2378349129, G261741909, The inactive X: discovering sex genes that influence female vulnerability to Alzheimer's disease, Wisconsin Registry for Alzheimer's Prevention, Menopause, Hormone Therapy and Clinicopathology: An In-Vivo Perspective, G49838260, G5021443450, Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension Study, G670286326, G689822645, G7855923974, G9000014521, G9000092144, G9000121663, G9000121865, G9000126385, G9000212218, The Longitudinal Course of Imaging Biomarkers in People At Risk for Alzheimer’s Disease, Wisconsin Registry for Alzheimer's Prevention, Building predictive algorithms to identify resilience and resistance to Alzheimer's disease, Menopause, hormone therapy and Alzheimer's disease clinicopathology: An in vivo perspective
OpenAlex ID: W7130339166