Associations of menopause hormone therapy with late-life cognition and brain health vary by formulation and APOEε4 presence

A study examined the effects of menopausal hormone therapy (MHT) on cognitive function in 8,741 women over 70 years old, considering the genetic factor APOEε4, which is the strongest genetic predictor of Alzheimer's disease. Results showed that MHT's impact on cognition varies depending on the type of formulation and cognitive domain. Estradiol-based MHT provided greater benefits for APOEε4 carriers compared to conjugated equine estrogens. Neuroimaging analyses in 930 participants revealed a consistent pattern of more favorable associations (higher brain volume, cortical thickness; less white matter damage) in APOEε4 carriers taking estradiol-based MHT. The research suggests that mixed results from previous MHT studies are caused by improper exposure definition.