Estrogen-only therapy linked to lower Alzheimer's risk

A large observational study led by Stanford University researchers, published in Neurology, found that women who used estrogen-only menopausal hormone therapy had 35% lower odds of Alzheimer's disease neuropathologic change at autopsy and 39% lower odds of clinician-defined dementia. The study analyzed data from the National Alzheimer s Coordinating Center (NACC) autopsy cohort and the Alzheimer s Disease Data Initiative (ADNI) living cohort, including over 21,000 women. Estrogen-only therapy was also associated with higher amyloid-beta levels in blood and cerebrospinal fluid, indicating less amyloid deposition in the brain. The association was significant only in women without the APOE epsilon 4 genetic risk factor. The researchers emphasized the findings are observational and do not prove causation. Critics, including Pauline Maki of the University of Illinois Chicago, noted limitations such as healthy-user bias and conflicting randomized trial data from the Women s Health Initiative. The study was funded by the United States — National Institute on Aging.