Age of menopause and dementia risk in 10,832 women from the Swedish Twin Registry.

INTRODUCTION

An earlier age of menopause (AOM) is hypothesized to increase vulnerability to the neuropathological processes of dementia, which begin in midlife.

METHODS

We tested this hypothesis in a sample of 10,832 women from the Swedish Twin Registry, stratified by menopause etiology.

RESULTS

Survival models showed that a U-shaped association was present for women whose menopause occurred spontaneously. Sensitivity analyses conducted in hormone naïve, apolipoprotein E ε4+, and AOM restricted subsamples showed largely analogous patterns of results.

DISCUSSION

Supporting conclusions from basic research, our results suggest that estrogens (proxied here by AOM) influence several biological pathways mediating dementia disease processes. In line with trends in hormone research across the past century, our findings challenge the oversimplified "more-is-better" perspective on hormone exposure and highlight the need for cross-disciplinary approaches to better understand the interacting endocrine and biopsychosocial factors that underlie the association between AOM and dementia pathogenesis.

HIGHLIGHTS

We found a U-shaped association of timing of spontaneous menopause and dementia risk. We also found a negative linear association of age of induced menopause and dementia risk. Restriction to a hormone-naïve sample did not alter the pattern of results. Conducted exploration of the impact of common survival model parameter choices on results.