Serum autotaxin is associated with DHEAS and predicts longitudinal cognitive changes in older women: Analysis of the Arao cohort study

AimTo examine the determinants of serum autotaxin (ATX) levels in community-dwelling older adults, focusing specifically on endogenous adrenal steroids, and to investigate the cross-sectional and longitudinal associations between serum ATX levels, cognitive function, and depressive symptoms. MethodsData were obtained from community-dwelling older adults aged 65 years and older in Arao City, Japan (baseline: 1,488; follow-up: 730). Serum ATX and dehydroepiandrosterone sulfate (DHEAS) levels were measured, and cognitive function and depressive symptoms were assessed using the Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS). Multiple linear regression models were applied to examine any cross-sectional associations among serum ATX levels, adrenal steroids, and MMSE/GDS scores. Longitudinal analyses assessed whether baseline serum ATX levels predicted 6-year changes in MMSE and GDS scores, with additional sex-stratified analyses and propensity score matching conducted to address any potential follow-up bias. ResultsAfter adjusting for age and sex, DHEAS levels were inversely associated with ATX levels. Cross-sectional analyses identified no association between serum ATX levels and MMSE/GDS scores. However, longitudinal analyses demonstrated significant associations between baseline serum ATX levels and changes in MMSE scores, particularly among women, and remained significant after multivariate and propensity score-matched analyses. ConclusionThis study provides epidemiological evidence of an inverse association between DHEAS and ATX, indicating a potential link between adrenal endocrine function and ATX regulation. In older women, baseline serum ATX levels were associated with inter-individual variability in subsequent cognitive trajectories, indicating a potential role for ATX in age-related cognitive changes.