Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women

Abstract

Objective: To determine the association between age at surgical menopause and both cognitive decline and Alzheimer disease (AD) pathology in 2 longitudinal cohorts.

Methods: Female subjects from 2 longitudinal studies of cognitive decline (Religious Orders Study and Rush Memory and Aging Project) were included (total n = 1,884). The primary analysis examined the association between age at surgical menopause and decline in a global cognition score. Secondary analyses examined additional outcomes: 1) decline in 5 cognitive subdomains and 2) a global measure of the burden of AD pathology. In exploratory analyses, we examined the effect of hormone replacement therapy (HRT). We adjusted all models for age, education, smoking, and cohort and stratified by surgical vs natural menopause.

Results: For the 32% of subjects with surgical menopause, earlier age at menopause was associated with faster decline in global cognition (p = 0.0007), specifically episodic memory (p = 0.0003) and semantic memory (p = 0.002). Earlier age at menopause was also associated with increased AD neuropathology (p = 0.038), in particular neuritic plaques (p = 0.013). HRT use for at least 10 years, when administered within a 5-year perimenopausal window, was associated with decreased decline in global cognition. No associations were seen in women who had natural menopause.

Conclusions: Early age at surgical menopause was associated with cognitive decline and AD neuropathology. Ongoing studies should clarify the potential effect of HRT on this relationship.

Figure. Earlier surgical menopause is associated with worse slope of cognitive decline

Estimated slope of decline in global cognition according to age at surgical menopause, categorized by quantile, for a woman with the median age at enrollment (78 years) and educational level (16 years) of the Religious Orders Study and Memory and Aging Project cohorts. The x-axis is study time, and the y-axis is the change in global cognitive performance from the baseline at study entry. An earlier age at surgical menopause is associated with both a steeper slope of decline during the study and a lower intercept, which suggests that a substantial amount of decline has occurred prior to study enrollment. The slope of cognitive decline for women undergoing natural menopause at any age is included as a reference.