Associations between hormone therapy use and tau accumulation in brain regions vulnerable to Alzheimer’s disease
Gillian Coughlan, Zoe B. Rubinstein, Hannah M Klinger, Kelly A. Lopez, Stephaine Hsieh, Rory Boyle, Mabel Seto, Diana L Townsend, Danielle V. Mayblyum, Emma G. Thibault, Heidi I.L. Jacobs, M. Farrell, Jennifer S. Rabin, Kathryn V. Papp, Rebecca E. Amariglio, Suzanne L. Baker, Cristina Lois, Dorene M. Rentz, Julie C. Price, Aaron P. Schultz, Michael J Properzi, Keith A. Johnson, Reisa A. Sperling, Rachel F. Buckley
Abstract
Elucidating the downstream impact of exogenous hormones on the aging brain will have far-reaching consequences for understanding why Alzheimer’s disease (AD) predominates in women almost twofold over men. We tested the extent to which menopausal hormone therapy (HT) use is associated with later-life amyloid-β (Aβ) and tau accumulation using PET on N = 146 baseline clinically normal women, aged 51 to 89 years. Women were scanned over a 4.5-year (SD, 2.1; range, 1.3 to 10.4) and 3.5-year (SD, 1.5; range, 1.2 to 8.1) period for Aβ and tau, respectively, ~14 years after the initiation of HT. In older women (aged >70 years), HT users exhibited faster regional tau accumulation relative to non-users, localized to the entorhinal cortex and the inferior temporal and fusiform gyri, with an indirect effect of HT on cognitive decline through regional tau accumulation. In younger women (aged <70 years), HT associations with tau accumulation were negligible. Findings are relevant for optimizing menopausal treatment guidelines.