HRT and menopausal dementia risk may be linked to brain changes

A Cambridge-led study of nearly 125,000 women, including about 11,000 MRIs, found reduced grey matter in brain regions tied to memory after menopause; the authors report HRT did not prevent this loss and experts say the evidence on dementia risk remains mixed.

Researchers report brain changes during the menopausal years that affect regions involved in memory and emotional regulation. The study, led by Professor Barbara Sahakian at the University of Cambridge and published in Psychological Medicine, analysed data from almost 125,000 women, including about 11,000 MRI scans. The authors observed reduced grey matter volume in key brain regions when comparing pre- and postmenopausal women. The question raised is whether those changes relate to later dementia risk and whether hormone replacement therapy (HRT) modifies that link. Key findings: - The study analysed nearly 125,000 women, with about 11,000 having MRI scans, and reported reduced grey matter in regions tied to memory, learning and emotional regulation after menopause. - The authors suggested these menopausal brain changes might be one factor in the higher reported rates of dementia in women compared with men. - Study co-author Christelle Langley reported that HRT appeared to slow declines in psychomotor speed (reaction time) but the data did not show that HRT prevented the observed grey matter loss. - A December 2025 meta-analysis by Aimee Spector in The Lancet Healthy Longevity found no significant association between HRT and dementia risk or benefit; researchers and commentators say further research is needed. Summary: This large study identifies measurable brain changes in the menopausal years and raises questions about links to dementia risk. Evidence on whether HRT affects that risk is mixed, with limited signals on specific functions but no clear prevention of grey matter loss. Undetermined at this time.