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Papers: 6 Jan 2024 - 12 Jan 2024

2024 Jan 08

J Pain


Probable chronic pain, brain structure, and Alzheimer’s plasma biomarkers in older men.


Bell TR, Franz CE, Eyler LT, Fennema-Notestine C, Puckett OK, Dorros SM, Panizzon MS, Pearce RC, Hagler DJ, Lyons MJ, Beck A, Elman JA, Kremen WS


Chronic pain leads to tau accumulation and hippocampal atrophy in mice. In this study, we provide one of the first assessments in humans, examining the associations of probable chronic pain with hippocampal volume, integrity of the locus coeruleus (LC)-an upstream site of tau deposition-and Alzheimer’s Disease (AD)-related plasma biomarkers. Participants were mostly cognitively unimpaired men. Probable chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, 424 participants underwent structural MRI of hippocampal volume and LC-sensitive MRI providing an index of LC integrity (LC contrast-to-noise ratio [LC]). Analyses adjusted for confounders including major health conditions, depressive symptoms, and opioid use. Models showed that men with probable chronic pain had smaller hippocampal volume and lower rostral-middle-but not caudal-LC compared to men without probable chronic pain. Men with probable chronic pain also had higher levels of plasma total tau, beta-amyloid-42, and beta-amyloid-40 compared to men without probable chronic pain. These findings suggest that probable chronic pain is associated with tau accumulation and reduced structural brain integrity in regions affected early in the development of AD. PERSPECTIVE: Probable chronic pain was associated with plasma biomarkers and brain regions that are affected early in Alzheimer’s disease (AD). Reducing pain in midlife and elucidating biological mechanisms may help to reduce the risk of AD in older adults.