The role of estrogen in the development of age-related cognitive impairment and dementia

While evidence is conflicting, estrogen cannot be recommended for the treatment of dementia but may have a role in preserving cognitive functioning in older women. Estrogen may have a dementia-prevention effect after menopause based on epidemiologic studies (not primary prevention studies), but this is not an approved indication. At this point, the off-label prescribing of estrogen for cognitive decline in the absence of dementia is not a routine clinical practice and should be regarded as appropriate only within the context of a research study. Estrogen may be used in late-stage dementia to treat aggressive or sexually disinhibited behavior,⁴⁵ but this would not be considered a routine use in dementia patients. Estrogen use after menopause has been linked to increased risk of venous thrombosis, and this risk increases with age and years of estrogen treatment.⁴⁶ Therefore, if estrogen were to be used for the prevention of cognitive impairment, it may have to be started early (during or soon after menopause) and continued only until the risk of vascular and thrombolytic complications related to estrogen use begins to rise, possibly in the seventh decade. Variables such as the type of estrogen, the method of administration, and the timing of ET relative to the menopause transition may affect the success of estrogen in preserving cognition and will require further research to resolve. Also, the role of progesterone remains to be investigated. Evidence from our laboratory strongly suggests that beneficial effects of estrogen on cognition may be acting through salutary interactions with the brain cholinergic system, the same system that is responsible for the cognitive loss in AD.