Sex differences in tau deposition are apparent in clinically normal older adults. Whether hormone therapy (HT) and menopause influence this higher tau retention in women and whether this is contingent upon levels of Aβburden is unclear. We examined the association between Aβ and regional tau as a function of sex, HT-exposure, and age-at-menopause.
292 cognitively unimpaired individuals from the Wisconsin Registry for Alzheimer’s Disease (mean age 67.43; 193 women[66%]; 106 APOE ε4 carriers[37%]) who underwent dynamic0-70[C-11] Pittsburgh Compound-B [PiB] and [F-18]-MK-6240 PET were enrolled. PiB reflects cortical Aβ. 98[46.6%] women reported use of HT(past/current). Eight tau-PET regions were selected(Fig1). Linear regressions (covarying age) examined the sex*PiB interaction for each tau-PET outcome and a preclinical Alzheimer’s cognitive composite (PACC). Similar models investigated HT*PiB and age-at-menopause*PiB interactions on the same outcomes.
Women exhibited higher tau-PET with an increasing PiB relative to men (FDR p’s:<0.002;Fig 1). The HT*PiB analyses indicated that women with a higher PiB and self-reported HT-use exhibited higher tau (Fig2). Women who initiated therapy >6years after menopause had greater tau retention and worse PACC performance. The age-at-menopause*PiB interaction was significant in all regions and for the PACC (Fig3).
When Aβ was elevated, HT-use and earlier age-at-menopause was associated with higher tau and worse cognition.