A PET study has revealed that women over the age of 70 who took menopausal hormone therapy (HT) more than a decade before have faster brain tau accumulation — a key indicator of Alzheimer’s disease.
The finding could help explain why Alzheimer’s disease predominates in women almost twofold over men, noted lead author Gillian Coughlan, PhD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.
“The findings may inform [Alzheimer’s disease] risk discussions relating to women’s reproductive health and treatment,” the group wrote. The study was published March 5 in Science Advances.
Alzheimer’s disease dementia is estimated to affect 13.8 million Americans by 2060, almost two-thirds of whom will be women, the authors noted. Growing evidence suggests that this may be due to the earlier accumulation of brain tau protein compared to men, yet the mechanisms that influence this remain unclear, they explained.
Moreover, currently, approximately a quarter of postmenopausal women who are 70 years and older have a history of HT use and have now entered a critical age of risk for Alzheimer’s disease, the authors added.
The researchers aimed to investigate whether menopausal HT use is associated with later-life tau accumulation. The group analyzed flortaucipir (Tauvid, Avid Pharmaceuticals) PET scans acquired over a 3.5-year period from 73 women who had used HT an average 14 years prior and 73 age-matched women who had not used HT. Participants were clinically unimpaired and between ages 51 and 89 at the beginning of the study.
According to the results, HT users over 70 years old exhibited faster regional tau accumulation relative to older nonusers. Specifically, affected regions included the entorhinal cortex, the inferior temporal gyrus, and the temporal fusiform gyrus, brain regions significantly associated with early stages of Alzheimer’s disease. The difference was not seen in women younger than 70, the researchers noted.
Moreover, the differences between HT users and nonusers remained after adjusting for potentially confounding factors such as the influence of baseline body mass index, years of education, APOEε4 status (a susceptibility gene), and vascular health over time, the group added.
“Among a cohort of clinically unimpaired women, faster regional tau accumulation was associated with self-reported history of menopausal HT use in older women, with minimal to no associations present in younger women,” the group wrote.
Ultimately, however, the researchers noted that the observational design of the study precludes the ability to draw causal links between menopausal HT and Alzheimer’s disease pathological progression. Future research is warranted, they wrote.
“In the context of a plethora of evidence for female vulnerability to tauopathy, these findings highlight a potential biological pathway for future investigation,” the authors concluded.
The full study is available here.