Public Health.

Area of Science:

• Neuroscience
• Epidemiology
• Women's Health

Background:

• Alzheimer's disease and related dementias (ADRD) disproportionately affect women.
• Menopause, occurring midlife, involves hormonal shifts that may influence neuroprotection and ADRD risk.
• Surgical menopause, induced by reproductive surgeries, presents a sudden hormone decline and a potential modifiable risk factor for ADRD.

Purpose of the Study:

• To investigate the association between menopausal type (natural vs. surgical) and age at menopause with physician-adjudicated diagnoses of Alzheimer's disease and related dementias (ADRD).

Main Methods:

• Prospective cohort study of 3371 women aged 65+.
• Self-reported data on menopausal age, surgical history, and hormone therapy use.
• Physician adjudication of ADRD diagnoses in a sub-sample, with imputation for the remainder.
• Cox proportional hazard models were used to analyze associations, controlling for hormone use, demographics, and health behaviors.

Main Results:

• Older age at menopause was associated with a modest reduction in ADRD hazard, though this became non-significant in fully adjusted models.
• Surgical menopause was significantly associated with a higher hazard of ADRD (HR=1.15 [1.04,1.25] in fully adjusted models).
• In models including both age and type of menopause, surgical menopause remained a significant positive predictor of ADRD risk.

Conclusions:

• Older age at menopause may offer a modest protective effect against ADRD, independent of menopausal type.
• Reproductive surgeries leading to surgical menopause are linked to an increased risk of developing ADRD.
• Further research with precise menopausal measures is needed, but findings suggest surgical menopause is a significant risk factor for ADRD.