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HRT & Cognitive Health

iStock-1387342690Recent research suggests that hormone replacement therapy (HRT) may have a positive impact on brain volume and reduce the rate of cognitive decline in women carrying the APOE4 genotype, the most common genetic determinant of the risk of cognitive decline.

The risk of cognitive decline is higher in women than men with a decline of estrogen at the time of menopause implicated in the acceleration of neuropathologies. Previous research into the role of HRT in the prevention of cognitive decline has shown conflicting results with some potential negative outcomes. However, adverse findings regarding HRT and cognition appear to predominantly relate to studies involving participants over 60 years. A small number of recent studies (mostly pre-clinical) offer potential insight into these disparities in results, suggesting the APOE genotype and age at which HRT use begins as possible factors modulating its efficacy against cognitive decline.

This study sought to investigate whether the two factors above may impact cognitive response to HRT. Baseline data were analyzed from female participants (over the age of 50 years and with no diagnosis of cognitive health issues) of the European Prevention of Alzheimer’s Dementia (EPAD) study. The analysis assessed the independent and combined impact of the APOE4 genotype and HRT on cognitive test results.

Results demonstrated potential modulatory effects of the APOE genotype and age of HRT introduction on the impact of HRT on cognitive function and brain volume. APOE4 carriers using HRT demonstrated less memory delay than non-HRT users with the APOE4 genotype. Researchers also reported that APOE4 participants were more responsive to HRT than those without this genotype. Earlier introduction of HRT was also found to be associated with increased brain volume in APOE4 carriers only.

The study concluded that women with the APOE4 genotype are more responsive to the potential positive effects of HRT on brain volume and cognitive decline than those without the genotype. They suggest results support the use of targeted prevention and treatment strategies for those in high-risk subgroups such as those carrying the APOE4 genotype. However, they acknowledge the small scale of this study and the need for further investigation to confirm findings.

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