Early menopause, later start to hormone therapy may increase risk of Alzheimer’s disease
Women are more likely than men to develop Alzheimer’s disease (AD), with women making up two-thirds of the population living with AD. A new study, led by Mass General Brigham researchers, sheds light on the relationship between the risk of Alzheimer’s disease and age of menopause and use of hormone therapy (HT). The results, published in JAMA Neurology, indicate that early age at menopause may be a risk factor for AD dementia, but that women who were prescribed HT around the age of menopause onset did not show increased risk.
The researchers used data from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), one of the few longitudinal studies on AD dementia that includes detailed information on menopause and HT use as well as PET neuroimaging. They analyzed PET scans from 292 cognitively unimpaired adults to determine levels of amyloid and tau in seven regions of the brain. Tau, which is known to be present in greater quantities in women compared to men in these brain regions, was the primary focus of the investigation, as its presence may offer insight into the sex-specific aspects of AD dementia and the risks that post-menopausal women may experience, even before they begin to display symptoms of cognitive decline.
As expected, women had greater levels of tau compared to men of the same age, especially in cases where they also had elevated β-amyloid. But the researchers also found that the association between abnormal levels of β-amyloid and tau was much stronger in women who had earlier menopause onset, even after adjusting for known causes of premature menopause, such as smoking and oophorectomy, and even genetic risk factors for AD dementia. Notably, tau levels were high in the entorhinal and inferior temporal regions, which are located close to the memory-center of the brain and are known to be involved in the progression of AD dementia. Given that many women who undergo premature menopause use HT, the researchers examined whether HT use was associated with β-amyloid and tau. While they did confirm this association, they observed that late initiation of HT — five years or more after menopause — drove this relationship. Many women in the late-HT-initiation group began HT close to a decade after menopause.
