Sex-specific trajectories and variability of pain burden in relation to cognitive decline and depressive symptoms in older adults: a prospective cohort study from health and retirement study.

BACKGROUND: Chronic pain is highly prevalent in middle-aged and older adults and is frequently accompanied by depressive symptoms and cognitive decline. Its long-term impact on cognitive and psychological trajectories remains incompletely understood, and sex-specific associations are underexplored.

METHODS: Using data from the Health and Retirement Study, we constructed pain-score trajectories and assessed their variability among 20,146 participants, and evaluated their association with study outcomes in 6,960 participants. Longitudinal pain trajectories were identified using cubic polynomial latent class mixed models, while within-person variability in pain was quantified using Variability Independent of the Mean (VIM). Depressive symptoms was assessed via the 8-item Center for Epidemiologic Studies Depression scale, and cognitive function was measured across memory, executive function, and orientation domains using a Telephone Interview for Cognitive Status (TICS)-style battery. Individual domain scores were converted to standardized z-scores and aggregated into a global cognition score. Linear mixed-effects models evaluated associations of pain trajectories and VIM with longitudinal changes in cognitive and psychological outcomes, with sex-stratified analyses conducted to examine potential differences.

RESULTS: Three distinct pain trajectories were identified: Fluctuation, Low-level, and High-level, with notable sex differences in trajectory proportions. Participants in the high-level trajectories exhibited the poorest cognitive performance and greatest depressive symptom burden. Over follow-up, trajectory class alone was not consistently associated with global cognitive decline in the overall sample but predicted increases in depressive symptoms, particularly among men. Greater within-person pain variability (higher VIM) consistently predicted faster decline in global cognition and greater increases in depressive symptoms. Sex-stratified analyses revealed heterogeneity: in men, high-level trajectories and higher VIM were linked primarily to declines in executive and global cognition and worsening depressive symptoms; in women, high-level trajectories and greater VIM were associated with accelerated decline in global cognition, memory, and orientation, with weaker associations for depressive change.

CONCLUSIONS: Sustained high pain burden and temporal variability in pain are important predictors of cognitive deterioration and depressive symptoms in older adults, with distinct sex-specific patterns. Incorporating dynamic pain features into risk assessment and implementing sex-sensitive interventions may facilitate early identification of at-risk individuals and mitigate subsequent cognitive and mental health decline.