Menopause status and its role in incident Alzheimer’s disease and related dementias, rheumatoid arthritis (RA) disease severity, and overall mortality in women with RA

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INTRODUCTION/OBJECTIVES: We aimed to investigate associations between menopausal characteristics, including age at menopause and cause (natural vs. artificial), with long-term outcomes in women with rheumatoid arthritis (RA), incident Alzheimer's disease and related dementias (ADRD), RA severity, and overall mortality. We hypothesized that atypical menopausal characteristics increase ADRD risk and disease severity. METHODS: Women with incident RA in 1980-2014 who were ≥50 years of age at RA incidence were included. Menopause cause and age at menopause (categorized as <45, 45-54, ≥55 years) were abstracted from medical records. Associations between menopausal characteristics and ADRD, extra-articular manifestations (ExRA), erosions, cardiovascular events, and mortality were evaluated using Cox models. Associations with clinic visits for flares and remissions were assessed using mixed-effects models. Data were collected using the Rochester Epidemiology Project medical records-linkage system. RESULTS: Both early/premature and late menopause were associated with nonsignificant near two-fold increases in ADRD risk. In addition, early/premature (HR 2.40; 95% CI 1.15-5.01) and late menopause (HR 2.17; 95% CI 1.01-4.66) significantly increased severe ExRA risk. Menopausal characteristics were not associated with presence of erosions or mortality. Artificial menopause was associated with fewer cardiovascular events and fewer visits for RA remission. Early/premature menopause was associated with fewer remission visits (OR 0.50; 95% CI 0.29-0.87). CONCLUSION: Women with early/premature and late menopause had nonsignificant, increased risk of incident ADRD. Menopausal characteristics had significant associations with RA severity and cardiovascular events, and may be relevant contextual factors in long-term risk assessment for women with RA.

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