Polymorphisms in genes associated with estrogen receptor activity and in genes for estrogen biosynthesis affecting endogenous estrogen are related to age at onset and cumulative incidence of dementia, and may serve as biomarkers of risk.
Taken together, the above results clearly demonstrated an mTORC2-dependent regulation of actin polymerization that contributed to the effects of ERα and ERβ on spatial learning, which may provide a novel target for the prevention and treatment of E2-related dementia in the aged population.
The association between five ESR α (ESR1) and β (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry.
Significant association was found between ESR1 polymorphisms (rs9340799 [ESR1+351], rs1801132 [ESR1+975], rs6557171, rs9397456, and rs1884049) and subjects with no dementia (Clinical Dementia Rating, CDR 0) and very mild dementia (CDR 0.5).
The relationships between ESR1 and cognitive impairment tend to be specific to or driven by women and restricted to risk for Alzheimer disease rather than other dementia causes.
Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.