Multisite Chronic Pain Accelerates Cognitive Decline Particularly in Apolipoprotein E E4 Allele Carriers

Chronic pain is a risk factor for cognitive decline and dementia, but whether risk is related to specific versus multisite location is unclear. Multisite chronic pain is theorized to involve hyper-excitability in pain receptors and pain processing brain regions, possibly caused by neuroinflammation. These factors may increase vulnerability to cognitive decline, particularly in those at elevated risk for Alzheimer’s disease. We examined how multisite chronic pain relates to cognitive decline in older adults and the moderating role of APOE-ε4 allele status, the major genetic risk factor for Alzheimer’s disease. We examined 751 participants without dementia at baseline from the Religious Orders Study/Memory and Aging Project (Mean age=79.47, SD=6.93, Mean education=6.42, SD=3.63; 64% women) followed for up to 30 years with repeated cognitive testing measuring episodic memory, working memory, perceptual orientation, and processing speed (Mean years followed=7.32, SD=4.51). Multisite chronic pain was defined as joint pain in >2 body regions over the first two study waves. Multisite chronic pain (n=105) was related to accelerated decline in episodic memory (b=-.03, p=.016) and processing speed (b=-.06, p<.001), particularly in APOE-ε4-positive individuals (bs=-.05 and -.04, respectively, ps<.01). Only APOE-ε4-positive individuals showed significant decline in perceptual orientation (b=-.08, p=.015). No single site pain was significantly associated with cognitive decline. Findings suggest that multisite chronic pain exacerbates cognitive decline in those at risk for Alzheimer’s disease. Future research is needed to understand the underlying etiology and whether it involves neuroinflammation and neurodegeneration. Funding: National Institute on Aging K01AG081559.