The risk of dementia is higher in women than in men. The metabolic consequences of the decline in estrogen during menopause accelerate this neuropathology in women. However, the use of hormone replacement therapy gives contradictory results in the prevention of cognitive decline.
Hormone replacement therapy (HRT) is usually used to treat symptoms associated with female menopause. Within 10 years of menopause, hormone replacement therapy may reduces all-cause mortality and the risk of coronary heart disease, osteoporosis and dementia. But after 10 years, the beneficial effects on mortality and coronary heart disease are no longer apparent.
In this new publication, the authors study the modulating role of APOE genotype and age at the start of hormone replacement therapy on the heterogeneity of the cognitive response to hormone replacement therapy.
The analysis used baseline data from participants in the European Alzheimer's Dementia Prevention Cohort. Covariate pattern analysis was used to test the impact of APOE genotype and hormone replacement therapy on certain cognitive tests, such as MMSE, RBANS, score counting, the Four Mountain test, and the of the supermarket trolley, as well as the volumes of the medial temporal lobe by MRI.
APOE4 hormone replacement therapy users had the highest RBANS Delayed Memory Index score compared to APOE4 HRT non-users and APOE4 non-carriers, with entorhinal and amygdala volumes 6-10% greater important. Earlier initiation of hormone replacement therapy was associated with greater right and left hippocampal volumes only in APOE4 carriers.
Thus the introduction of hormone replacement therapy seems to be associated with delayed memory improvement and greater brain volumes only in in APOE4 carriers.
This may represent an effective targeted strategy to mitigate the higher lifetime risk of Alzheimer's disease in this large at-risk population subgroup. Confirmation of the results of a fit-for-purpose RCT with prospective recruitment based on APOE genotype is needed to establish causation.
We should remember that some studies on hormone replacement therapy seem to show that the risks could outweigh the benefits. It has been suggested that many of the positive perceptions of hormone replacement therapy may be due to the efforts of pharmaceutical companies including by publishing biased scientific publications.