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Public Health.

Alexis Reeves1, Oscar L Lopez2,3,4,5, Michelle D Shardell6

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Summary
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Older age at menopause may slightly lower Alzheimer's disease and related dementias (ADRD) risk. However, surgical menopause significantly increases ADRD risk in women, highlighting a potential modifiable factor.

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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.