Abstract
Chronic pain is increasingly recognized as a potential risk factor for cognitive decline, yet findings from observational studies are inconsistent. We conducted a meta-analysis to evaluate the long-term association between chronic pain and cognitive impairment. PubMed, Embase, and the Cochrane Library were searched from inception to January 2025 for longitudinal cohort studies assessing this relationship. Twenty-eight eligible cohorts comprising 7,914,407 participants were included. Adjusted odds ratios (ORs) were pooled using random-effects models; subgroup, sensitivity, and meta-regression analyses were performed to explore heterogeneity. Chronic pain was associated with a higher risk of cognitive impairment (pooled adjusted OR = 1.30; 95% CI: 1.14-1.47), an effect driven by dementia (pooled OR = 1.43; 95% CI: 1.23-1.65) rather than by global cognitive performance scores (pooled OR = 0.99; 95% CI: 0.88-1.11). Associations were stronger in studies with follow-up ≥5 years (OR = 1.37), in older populations (OR = 1.30), and in cohorts focusing on headache-related pain (OR = 1.42). Meta-regression indicated that depression was a key moderator of the association. These findings suggest that chronic pain is linked specifically to an increased risk of dementia, particularly among older individuals and those with headache-related pain. Integrative clinical strategies addressing pain and co-occurring depression, along with mechanistic and interventional studies using standardized cognitive endpoints, are warranted.