Hormone therapy and cognitive impairment

Hormone replacement therapy (HRT) introduced early during the menopausal transition may protect against Alzheimer's dementia in women carrying the APOE4 gene.

Results from a cohort study ( Alzheimers Res Ther. Published online January 9, 2023) of almost 1200 women showed that use of HRT was associated with higher delayed memory scores and larger entorhinal and hippocampal brain volumes ― areas that are affected early by Alzheimer's disease (AD) pathology.

HRT was also found to be most effective, as seen by larger hippocampal volume, when introduced during early perimenopause.

Estrogen receptors are localized in various areas of the brain, including cognition-related areas. Estrogen regulates such things as neuroinflammatory status, glucose utilization, and lipid metabolism.

The decline of estrogen during menopause can lead to disturbance in these functions, which can accelerate AD-related pathology.

The researchers analyzed baseline data from participants in the European Prevention of Alzheimer's Dementia (EPAD) cohort. This project was initiated in 2015 with the aim of developing longitudinal models over the entire course of AD prior to dementia clinical diagnosis.

Although HRT carries risks, they can clearly be managed; and if it's proven that estrogen or hormone replacement around the time of the menopause can be protective against AD, the risk-benefit ratio of HRT could be in favor of treatment.