The Association of Osteoarthritis and Related Pain Burden to Incident Alzheimer’s Disease and Related Dementias: A Retrospective Cohort Study of U.S. Medicare Beneficiaries

Abstract

Background: Emerging evidence suggests osteoarthritis (OA) and related symptom burden may increase risk for Alzheimer's disease and related dementias (ADRD). However, longitudinal studies are sparse, and none have examined the potential mediating effects of mood or sleep disorders.Objective: To determine the association of OA and related pain to incident ADRD in U.S. elders. Methods:In this retrospective cohort study, we used baseline and two-year follow-up data from linked Medicare claims and Medicare Current Beneficiary Survey files (11 pooled cohorts, 2001-2013). The study sample comprised 16,934 community-dwelling adults ≥ 65 years, ADRD-free at baseline and enrolled in fee-for-service Medicare. Logistic regression was used to assess the association of OA and related pain (back, neck, joint, neuropathic) to incident ADRD, explore the mediating influence of mood and insomnia-related sleep disorders, and (sensitivity analyses) account for potential survival bias.Results: Overall, 25.5% of beneficiaries had OA at baseline (21.0% with OA and pain); 1149 elders (5.7%) were subsequently diagnosed with ADRD. Compared to beneficiaries without OA, those with OA were significantly more likely to receive a diagnosis of incident ADRD after adjustment for sociodemographics, lifestyle characteristics, comorbidities, and medications (adjusted odds ratio (AOR) = 1.23 (95% confidence interval (CI) 1.06, 1.42). Elders with OA and pain at baseline were significantly more likely to be diagnosed with incident ADRD than were those without OA or pain (AOR = 1.31, CI 1.08, 1.58). Sensitivity analyses yielded similar findings. Inclusion of depression/anxiety, but not sleep disorders, substantially attenuated these associations.

Prospective Evaluation of the Association Between Arthritis and Cognitive Functions in Middle-Aged and Elderly Chinese

“…Cohort studies that used dementia as the primary endpoint instead of cognitive impairment also addressed similar research questions. Two large cohort studies showed that osteoarthritis was associated with higher risk of dementia ( Huang et al, 2015 ; Innes and Sambamoorthi, 2020 ), which reinforces our finding solely for cognitive functions. A population-wide study with a 4-year follow-up in Chinese Taiwan showed participants with osteoarthritis ( n = 35,149) was 1.25 times as likely to develop dementia as participants without osteoarthritis ( n = 70,298) ( Huang et al, 2015 ), while another US study with a 2-year follow-up among 16,934 community-dwelling participants aged 65 years or older showed similarly higher risk of dementia for participants with osteoarthritis, particularly those with both osteoarthritis and pain ( Innes and Sambamoorthi, 2020 ).…”

“…Two large cohort studies showed that osteoarthritis was associated with higher risk of dementia ( Huang et al, 2015 ; Innes and Sambamoorthi, 2020 ), which reinforces our finding solely for cognitive functions. A population-wide study with a 4-year follow-up in Chinese Taiwan showed participants with osteoarthritis ( n = 35,149) was 1.25 times as likely to develop dementia as participants without osteoarthritis ( n = 70,298) ( Huang et al, 2015 ), while another US study with a 2-year follow-up among 16,934 community-dwelling participants aged 65 years or older showed similarly higher risk of dementia for participants with osteoarthritis, particularly those with both osteoarthritis and pain ( Innes and Sambamoorthi, 2020 ). In contrast to osteoarthritis, results for rheumatoid arthritis were less consistent: a nested case-control in Korea did not find evidence for the association of rheumatoid arthritis with dementia ( Min et al, 2020 ), while a population-wide cohort study in Chinese Taiwan showed a positive association for autoimmune rheumatic diseases ( Lin et al, 2018 ).…”

Persistent moderate to severe pain and long‐term cognitive decline

“…These studies typically used small sample sizes over a short time period or in a particular subpopulation, such as women (Luque-Reca et al, 2019), which may limit the generalizability of the results. Besides, prior researches only explored the relationship between baseline pain and incident cognitive impairments, rather than the trajectory of cognitive decline (Innes & Sambamoorthi, 2020;Moriarty et al, 2011), which consists of several evaluations of cognitive performance, is important for observing and assessing the advancement of cognitive deterioration and could, therefore, be more informative for early intervention.…”

Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease

“…Due to potential pharmacodynamic interaction between muscarinic antagonists and acetylcholinesterase inhibitors (AChEIs), AD patients with asthma/COPD might benefit more from memantine than AChEIs [ 53 , 56 ]. Osteoarthritis or other chronic non-cancer pain is associated with an elevated risk of AD-related dementia; this association is particularly pronounced in those with osteoarthritis and pain, and mood disorders may partially mediate this relationship [ 57 , 58 ]. Although studies have emphasized the importance of pain control for AD patients, pain management is still a dilemma because of the side-effects of opioids.…”