Background

Women have a higher risk of dementia than men. Reproductive factors may be implicated.

Objective

Determine the association between reproductive factors (earlier menarche, later menopause, longer reproductive lifespan (RLS), post-menopausal hormone replacement therapy [pmHRT] use, and serum estradiol/estrone) and neurocognitive and neuroimaging markers of brain aging and incident dementia in cognitively healthy women.

Methods

Lifetime reproductive factors were measured in dementia-free women [mean age 60.3 (SD 9.3) year] from the Framingham Heart Study Offspring cohort between 1998–2001 and related to concurrent neurocognitive (n = 1329) and MRI brain measures (n = 1165) using multivariable linear regression and risk of incident dementia (secondary outcome, n = 921) using Cox proportional hazards regression.

Results

Use of pmHRT (Beta (β, standardized regression coefficient)±standard error (SE), 0.14 ± 0.05, p = 0.009), elevated serum estradiol (0.06 ± 0.03, p = 0.02) and earlier menarche (≥14 years versus 12–13 years, −0.13 ± 0.06, p = 0.03) were associated with better abstract reasoning (Similarities). Older age at menopause (≥52 years versus the referent 50–51 years) (0.18 ± 0.09, p = 0.04), elevated serum estradiol (0.06 ± 0.03, p = 0.02), and 1–2 (0.17 ± 0.08, p = 0.03) or ≥3 (0.22 ± 0.08, p = 0.007) versus no live births were associated with superior visuospatial performance (Hooper's visual organization test). Earlier menopause age was associated with lower hippocampal volume (≤49 years versus 50–51 years, −0.11 ± 0.04, p = 0.02) while 1–2 (5.50 ± 1.95, p = 0.005) and ≥3 live births (β±SE, 4.94 ± 1.96, p = 0.01) were associated with greater total cerebral brain volume.

Conclusions

In general, greater exposure to estrogen throughout a woman's reproductive lifespan was associated with enhanced cognitive performance and larger brain volumes. Our results may suggest positive cognitive benefits of greater lifetime estrogen exposure, but require further validation.

Search results

The association between reproductive factors and neurocognitive and neuroimaging markers of brain aging