Background/Purpose: Alzheimer’s disease and related dementias present an increasing global health concern, with increasing incidence and prevalence. Hormonal fluctuations associated with menopause may exacerbate inflammatory and cerebrovascular changes, contributing to neurocognitive decline. Early and artificial menopause have been linked to elevated dementia risk and neurocognitive decline in the general population. Rheumatoid arthritis (RA) has been separately established as a risk factor for dementia. However, the specific relationship between menopause characteristics and dementia in populations with RA remains unclear. We aimed to evaluate the association between artificial and early menopause on occurrence of dementia in a population with RA.

Methods: This retrospective population-based study included women /=50 years of age with incident RA in 1980-2014 who met 1987 ACR criteria and had no previous diagnosis of dementia. Age at menopause was categorically defined as the age bracket of an individual (< 45, 45–54, and ≥55 years) at 6 months post-menstruation cessation for natural cases or at the time menopause was induced for artificial cases. Menopause data was manually collected from medical records. Women with unknown age at menopause were assigned to the 45-54 age bracket; women with unknown causes of menopause were classified as natural. Artificial menopause included those with bilateral oophorectomy or chemotherapy-induced menopause. Dementia was defined as two relevant ICD-9/ICD-10 codes at least 30 days apart. Cox proportional hazards models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence intervals (CI) between menopause and dementia. Individuals with early (< 45 years) or artificial menopause were compared to referents with natural or unknown-cause menopause at ≥45 years. Primary covariates included age and index year of RA incidence. To assess effect modification by RA severity and treatment, separate interaction models were performed examining the effects of RF/CCP positivity, erosions and/or destructive changes, severe extra-articular RA manifestations, or large joint swelling within one year.

Results: A total of 458 women were included, with a median age at RA incidence of 63.2 years. Sixty-six women had an outcome of dementia following RA diagnosis. Early and/or surgical menopause was present in 82 women (17.9%). Early or surgical menopause was associated with an increased risk of dementia (aHR 1.96; CI 0.99-3.89). Results were similar when adjusting for RF/CCP positivity, obesity, smoking, and education. For the interaction analyses, no statistically significant effect modifications were observed (all interactions P >0.05).

Conclusion: In women with RA, early or surgical menopause was associated with a nearly two-fold increase in risk of dementia, suggesting the need for increased awareness of increased risk for cognitive decline in this population of patients with RA. This association was not significantly modified by RA severity factors, smoking, education, or obesity.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-impact-of-early-and-artificial-menopause-on-dementia-risk-among-women-with-rheumatoid-arthritis/