Hormone replacement therapy and its association with LATE-NC in older adults.

INTRODUCTION: Limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) is a cause of dementia resembling Alzheimer's disease (AD). The 90+ Study found women using hormone replacement therapy (HRT) two to three decades before death had lower odds of LATE-NC. We attempted to replicate this finding in a different cohort. METHODS: Participants (n = 2056) included males (n = 640) and females (n = 1416) aged ≥65 from the Religious Orders Study and Memory and Aging Project with HRT and neuropathology data. We examined the association between HRT and LATE-NC in males and females and between HRT-related and reproductive variables in relation to LATE-NC in females using logistic regression. RESULTS: HRT use within 5 years before or after menopause (odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.50 to 0.98, p = 0.03) or for 8 to 16 years (OR = 0.44, 95% CI = 0.24 to 0.79, p = 0.006) was associated with lower odds of LATE-NC. DISCUSSION: This finding identifies a potential factor related to LATE risk and highlights the importance of HRT timing and duration for its potential neuroprotective effects.