Non-Cancer Chronic Pain Conditions and Risk for Incident Alzheimer’s Disease and Related Dementias in Community-Dwelling Older Adults: A Population-Based Retrospective Cohort Study of United States Medicare Beneficiaries, 2001–2013

Abstract

Accumulating evidence suggests that certain chronic pain conditions may increase risk for incident Alzheimer’s disease and related dementias (ADRD). Rigorous longitudinal research remains relatively sparse, and the relation of overall chronic pain condition burden to ADRD risk remains little studied, as has the potential mediating role of sleep and mood disorders. In this retrospective cohort study, we investigated the association of common non-cancer chronic pain conditions (NCPC) at baseline to subsequent risk for incident ADRD, and assessed the potential mediating effects of mood and sleep disorders, using baseline and 2-year follow-up data using 11 pooled cohorts (2001–2013) drawn from the U.S. Medicare Current Beneficiaries Survey (MCBS). The study sample comprised 16,934 community-dwelling adults aged ≥65 and ADRD-free at baseline. NCPC included: headache, osteoarthritis, joint pain, back or neck pain, and neuropathic pain, ascertained using claims data; incident ADRD (N = 1149) was identified using claims and survey data. NCPC at baseline remained associated with incident ADRD after adjustment for sociodemographics, lifestyle characteristics, medical history, medications, and other factors (adjusted odds ratio (AOR) for any vs. no NCPC = 1.21, 95% confidence interval (CI) = 1.04–1.40; p = 0.003); the strength and magnitude of this association rose significantly with increasing number of diagnosed NCPCs (AOR for 4+ vs. 0 conditions = 1.91, CI = 1.31–2.80, p-trend < 0.00001). Inclusion of sleep disorders and/or depression/anxiety modestly reduced these risk estimates. Sensitivity analyses yielded similar findings. NCPC was significantly and positively associated with incident ADRD; this association may be partially mediated by mood and sleep disorders. Additional prospective studies with longer-term follow-up are warranted to confirm and extend our findings.

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.…”

Increased Odds of Incident Alzheimer’s Disease and Related Dementias in Presence of Common Non-Cancer Chronic Pain Conditions in Appalachian Older Adults

“…Consistent with our findings, this study documented a strong, positive, dose–response association of perceived memory loss to osteoarthritis and associated joint pain, an association that appeared mediated in part by sleep and mood impairment. Likewise, published research regarding the collective and incremental relation of common NCPCs to incident ADRD remains sparse, to date limited to our recent study in a large sample of US elders enrolled in fee-for-service Medicare (Khalid et al, 2020). In this prior investigation, we found risk of ADRD to rise significantly with increasing number of pain conditions at baseline after adjusting for sociodemographic, lifestyle and comorbid conditions, and medication use (Khalid et al, 2020), with risk estimates similar overall to those observed in the current study of WV elders.…”

“…A growing body of evidence from experimental (Moriarty et al, 2011; Cao et al, 2019) and cross-sectional (Van Der Leeuw et al, 2015; Ikram et al, 2019) studies suggests significant neurocognitive impairment, including deterioration in attention, memory, and executive function with chronic pain and certain NCPCs, as well as adverse neurostructural and neurofunctional changes paralleling those implicated in ADRD pathogenesis (Ng et al, 2018; Cao et al, 2019). Longitudinal studies from North America (Whitlock et al, 2017; van der Leeuw et al, 2018; Ezzati et al, 2019; Khalid et al, 2020), Europe (Veronese et al, 2018), and East Asia (Yang et al, 2016; Tzeng et al, 2018; Yamada et al, 2019) also suggest significant associations of chronic pain and certain NCPCs to subsequent deterioration in memory (Whitlock et al, 2017; van der Leeuw et al, 2018), accelerated cognitive decline (Whitlock et al, 2017), new onset cognitive impairment (Whitlock et al, 2017; van der Leeuw et al, 2018), and incident ADRD (Ezzati et al, 2019; Innes & Sambamoorthi, 2020; Khalid et al, 2020).…”

“…Population-based evidence primarily focused on nationally representative populations (Whitlock et al, 2017; Khalid et al, 2020) with a small number of US-based studies conducted at county level (van der Leeuw et al, 2018; Ezzati et al, 2019); however, the longitudinal association of chronic pain to subsequent adverse cognitive outcomes remains underexplored in rural, underserved populations, who exhibit historically high prevalence of both chronic pain (Johannes et al, 2010; Goldberg & McGee, 2011; Jackson et al, 2014; Dahlhamer et al, 2018; Guglielmo et al, 2019) and ADRD risk factors (Shaw et al, 2004; Serrano et al, 2007; Schwartz et al, 2009; Centers of Disease Control (CDC) West Virginia - State Nutrition, Physical Activity, and Obesity Profile, 2012; Abner et al, 2016; Akushevich et al, 2018; Mamudu et al, 2017; Mattos et al, 2017).…”

Dor crônica e condições de vida dos idosos: um panorama da maior cidade da América do Sul

“…3,5 Em paralelo, a dor crônica é um grave problema porque tem uma alta prevalência, e gera uma incapacidade física e emocional nos indivíduos. 83 Nesta perspectiva, as evidências sugerem que a dor crônica pode aumentar o risco de declínio cognitivo e demência, 92,93 assim como consiste em um fator de risco para a morte prematura. 86 O conhecimento sobre a epidemiologia da dor ainda é escasso, principalmente, no que diz respeito ao nível socioeconômico.…”