O-248 Association between history of laparoscopically-confirmed endometriosis and cognitive function at middle-age

Abstract Study question Is history of laparoscopically-confirmed endometriosis associated with worse cognitive function in middle-aged women? Summary answer History of laparoscopically-confirmed endometriosis is associated with lower cognitive performance, more subjective cognitive complaints, and a higher risk of dementia later in life. What is known already Infertility, pregnancy complications including gestational diabetes, early menopause, and other non-communicable diseases associated with endometriosis have all been linked to cognitive impairment and dementia. However, it remains unknown whether endometriosis independently affects cognitive function and the risk of dementia later in life. There are plausible biological pathways through which endometriosis may impact cognitive health. Chronic systemic inflammation and pain, key features of endometriosis, have been implicated in accelerated cognitive aging. Recent evidence also suggests that rare cerebral endometriosis may directly cause neuropsychiatric symptoms. Study design, size, duration Prospective cohort study, the Nurses' Health Study II (1989–present; n = 116,429). Participants self-reported laparoscopically-confirmed endometriosis (>96% validation) on biennial questionnaires (1989–2013; n = 111,682). Objective cognitive function was subsequently assessed every 6–12 months using the computerized Cogstate Brief Battery in a sub-cohort (2014–2022; n = 19,805). Subjective cognitive function was assessed in 2017 using a 6-item questionnaire on recent memory and cognition changes (n = 67,639). Dementia diagnoses were determined through self-reports or death certificates (2013–2019; n = 75,472). Participants/materials, setting, methods Primary analysis included 19,805 women who completed baseline and ≥1 follow-up assessment (range, 1-8 assessments). Task scores were z-scored, with higher scores indicating better functioning. Primary outcomes were cognitive score at baseline and cognitive change (i.e., decreased cognitive score during follow-up). Secondary analyses included participants who responded to questionnaires regarding subjective cognitive function (range, 0-6 complaints) and dementia. We used linear mixed-effects and log-binomial models to estimate the associations between endometriosis and cognitive outcomes. Main results and the role of chance Participants were predominantly white (96%) with a mean (SD) age of 62.8 (4.9) years at their baseline Cogstate assessment. After adjusting for age, educational attainment, racial identity, age at menarche, and BMI at 18 years, individuals with a history of endometriosis, versus those without, had lower global cognition at baseline (β=-0.05 SD, 95% CI: -0.08, -0.03) but did not have faster cognitive change during the 8-year follow-up (β = 0.00 SD/year, 95% CI: -0.01, 0.01). The associations between endometriosis and baseline global cognition were stronger among the 447 pre-menopausal women (β (95% CI): -0.28 SD (-0.53, -0.04)) than post-menopausal women (-0.05 SD (-0.08, -0.02), P additive interaction=0.06). In contrast, we found no evidence of effect modification by comorbid infertility (P additive interaction=0.50). Endometriosis was also associated with more subjective cognitive complaints (having ≥4 (2.0%) vs. <4 complaints (98.0%), RR = 1.50, 95% CI: 1.30, 1.73) and elevated risk of dementia (0.3% cases, RR = 1.99, 95% CI: 1.41, 2.81). The magnitude of associations between endometriosis and all cognitive outcomes were comparable to associations reported in the literature for people with hypertension. Results were moderately attenuated but remained significant after further adjustment of several mediators, including physical activity, diet, parity, menopausal status, and comorbidities (e.g., diabetes, depression). Limitations, reasons for caution We did not have measures of the subphenotypes of endometriosis and therefore were not able to explore differences in cognitive health by endometriosis-specific characteristics. Dementia was mostly self-reported, and power was limited for this outcome. Wider implications of the findings In middle-aged women, we observed worse baseline global cognition, more subjective cognitive complaints, and higher risk of dementia among individuals with endometriosis. These results highlight the need for future research to investigate the biological link between endometriosis and cognitive decline and whether managing endometriosis symptoms mitigates cognitive risks. Trial registration number No