The Potential Contribution of Chronic Pain and Common Chronic Pain Conditions to Subsequent Cognitive Decline, New Onset Cognitive Impairment, and Incident Dementia: A Systematic Review and Conceptual Model for Future Research

Background: Growing evidence suggests that chronic pain and certain chronic pain conditions may increase risk for cognitive decline and dementia. Objective: In this systematic review, we critically evaluate available evidence regarding the association of chronic pain and specific common chronic pain conditions to subsequent decline in cognitive function, new onset cognitive impairment (CI), and incident Alzheimer's disease and related dementias (ADRD); outline major gaps in the literature; and provide a preliminary conceptual model illustrating potential pathways linking pain to cognitive change. Methods: To identify qualifying studies, we searched seven scientific databases and scanned bibliographies of identified articles and relevant review papers. Sixteen studies met our inclusion criteria (2 matched case-control, 10 retrospective cohort, 2 prospective cohort), including 11 regarding the association of osteoarthritis (N=4), fibromyalgia (N=1), or headache/migraine (N=6) to incident ADRD (N=10) and/or its subtypes (N=6), and 5 investigating the relation of chronic pain symptoms to subsequent cognitive decline (N=2), CI (N=1), and/or ADRD (N=3). Results: Studies yielded consistent evidence for a positive association of osteoarthritis and migraines/headaches to incident ADRD; however, findings regarding dementia subtypes were mixed. Emerging evidence also suggests chronic pain symptoms may accelerate cognitive decline and increase risk for memory impairment and ADRD, although findings and measures varied considerably across studies. Conclusion: While existing studies support a link between chronic pain and ADRD risk, conclusions are limited by substantial study heterogeneity, limited investigation of certain pain conditions, and methodological and other concerns characterizing most investigations to date. Additional rigorous, long-term prospective studies are needed to elucidate the effects of chronic pain and specific chronic pain conditions on cognitive decline and conversion to ADRD, and to clarify the influence of potential confounding and mediating factors.