Accelerated Cognitive Decline in Pain-Insomnia-Depression Syndrome: Longitudinal Evidence and Protective Effects of Healthy Lifestyles

OBJECTIVES: To investigate the longitudinal association between Pain-Insomnia-Depression Syndrome (PIDS) and cognitive decline, assess the dose-response relationship associated with cumulative symptom load, and examine the potential protective role of healthy lifestyles. DESIGN: Population-based prospective cohort study. SETTING AND PARTICIPANTS: A total of 7565 participants aged 50 years and older from the English Longitudinal Study of Ageing, with a follow-up period of up to 9 years. METHODS: PIDS burden was defined in 2 complementary ways: the presence of PIDS (all 3 conditions present) and cumulative symptom load (ranging from 0 to 3 conditions). Cognitive domains, including episodic memory, executive function, and temporal orientation, were assessed using standardized z scores. Lifestyle factors (smoking, alcohol intake, physical activity, diet) were combined into a composite score and categorized as healthy (3-4 factors) or unhealthy (0-2 factors). Linear mixed-effects models were used to estimate baseline differences and rates of cognitive change. RESULTS: Participants with PIDS exhibited significantly lower baseline global cognitive function (β, -0.171; 95% CI, -0.245 to -0.098) and experienced a more rapid cognitive decline (β, -0.050 SD/year; 95% CI, -0.069 to -0.031). For cumulative symptom load, a clear dose-response pattern was observed in global cognition: 1 symptom predicted a decline of β, -0.019 SD/year; 95% CI, -0.030 to -0.008, 2 symptoms predicted β, -0.031 SD/year; 95% CI, -0.044 to -0.018, and 3 symptoms β, -0.064 SD/year; 95% CI, -0.084 to -0.044. Notably, adherence to healthy lifestyles attenuated these negative effects, with PIDS participants maintaining healthy lifestyles exhibiting a slower rate of cognitive decline (β, 0.055 SD/year; 95% CI, 0.015 to 0.095). CONCLUSION AND IMPLICATIONS: PIDS and higher cumulative symptom load are associated with accelerated cognitive decline in middle-aged and older adults. Healthy lifestyle adherence mitigates these effects, underscoring integrated strategies combining symptom management with lifestyle interventions to reduce dementia risk.