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. Survival models showed that a U-shaped association was present for women whose menopause occurred spontaneously. Sensitivity analyses conducted in hormone naïve, 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) interact with 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. Specifically, the non-linear association we observed between AOM and dementia risk points to the involvement of distinct and interacting biological mechanisms beyond just estrogen levels.