dementia risk

natural menopause

incident dementia

verbal memory

Alzheimers & Dementia

Background The female reproductive period – menarche to menopause – can serve as a proxy for lifetime endogenous estrogen exposure. A foreshortened reproductive period, either naturally or secondary to medical intervention, has been associated with an increased risk of Alzheimer’s disease (AD), supporting the hypothesis that estrogen exposure is neuroprotective. Prior studies have been limited by small sample sizes, and confounding effects of exogenous hormone exposure (e.g., oral contraception or hormone replacement therapy). In the present study, we examined the association between the length of the reproductive period and dementia in a large, population‐based sample of exogenous hormone naïve women from the Swedish Twin Registry (STR). Method Participants were 7,630 women who provided self‐reported health and reproductive history data as part of the Screening Across the Lifespan Twin (SALT) project. Subsequent dementia diagnoses were obtained through follow‐up studies that leveraged either in‐house clinical assessments or national health registry data. Mixed effects logistic regression models examined the effect of length of the reproductive period on all‐cause dementia and AD diagnoses while controlling for the non‐independence of the twin data. Analyses controlled for birth year, number of pregnancies, and history of surgical menopause (i.e., oophorectomy). Result The prevalence of all‐cause dementia and AD within the sample was 15.2% and 7.7%, respectively. The mean age at participation in SALT was 65.6 years (SD=9.9), and mean age at dementia diagnosis was 83.4 (SD=7.3). Reproductive span averaged 35.4 years (SD=5.2), and 7.4% of the sample reported surgical menopause. Shorter reproductive span was significantly related to increased likelihood of all‐cause dementia (p=.0008) and AD (p=.0012). Relationships were non‐linear, such that the added benefit of longer reproductive span on dementia/AD risk waned within the higher range of reproductive span. Premature menopause (prior to age 40), significantly incre...

Lifetime endogenous estrogen exposure in women influences risk of dementia