Study Shows Longer Reproductive Period Put Women at Greater Risk for Alzheimer’s Disease

Estrogen has been thought to play a role in a woman’s risk of developing Alzheimer’s disease. A new study has taken a different approach to identify risk factors for Alzheimer’s disease by examining the association between a woman’s reproductive life span as an indicator of endogenous estrogen exposure and levels of cerebrospinal fluid biomarkers. Study results are published online in Menopause, the North American Menopause Society (NAMS).

Alzheimer’s disease represents 60% to 70% of all dementia diagnoses, making it the most common form of dementia. Approximately two-thirds of those with Alzheimer’s disease are women. This is not surprising because age is the greatest known risk factor for Alzheimer’s disease, and women tend to live longer than men.

The incidence of Alzheimer’s disease is rising quickly because of the ageing population, so multiple studies have been undertaken to identify other risk factors, especially those that may explain sex differences. Prior studies have shown a link between higher and lower estradiol blood levels and risk of dementia, whereas others have identified no associations. Some studies have shown that hormone therapy after menopause can increase the risk of dementia, but others have documented a decreased risk. Similarly, cognitive decline has been linked with both longer and shorter reproductive periods.

Despite all the conflicting evidence, few, if any, studies have examined the association between estrogen and biomarkers for Alzheimer’s disease in cerebrospinal fluid, the clear body fluid found within the tissues surrounding the brain and spinal cord.

In this new study, a small sampling of women freed of dementia and underwent natural menopause was followed for 25 years. Based on the results from the cerebrospinal fluid samples, researchers concluded that a longer reproductive life was associated with increased levels of Alzheimer’s disease biomarkers in the preclinical phase of the disease; however, they suggested that larger studies should be conducted to confirm these findings.

‘This small population-based study showed an association between duration of the reproductive life span (a surrogate marker for exposure to endogenous estrogen) and biomarkers of Alzheimer disease in the cerebrospinal fluid of women without dementia. This finding needs to be confirmed in larger studies. Still, maybe another factor contributing to the increased burden of Alzheimer’s disease in women that, at least in part, likely relates to ageing and the longer life expectancy in women compared with men,’ says Dr Stephanie Faubion, NAMS medical director.