{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:40:23Z","timestamp":1790347223232,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Debate surrounds the role of chronic pain as a risk factor for cognitive decline and dementia. This study aimed at examining the association of chronic pain with biomarkers of neurodegeneration using data from the Alzheimer's Disease Neuroimaging Initiative.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants were classified using the ATN (amyloid, tau, neurodegeneration) classification. Chronic pain was defined as persistent or recurrent pain reported at baseline. For each ATN group, analysis of covariance models identified differences in cerebrospinal fluid (CSF) levels of amyloid \u03b2<jats:sub>1\u201342<\/jats:sub>, phosphorylated tau 181 (ptau<jats:sub>181<\/jats:sub>), total tau (t\u2010tau), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and cognitive function between chronic pain states. Differences in CSF levels of inflammatory markers between chronic pain states were further analyzed. Linear mixed effect models examined longitudinal changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The study included 995 individuals, with 605 (60.81%) reporting chronic pain at baseline. At baseline, individuals with suspected non\u2010Alzheimer pathophysiology and chronic pain showed increased CSF levels of t\u2010tau and sTREM2. Chronic pain was associated with increased tumor necrosis factor \u03b1 levels, irrespective of the ATN group. Longitudinally, an increase in ptau<jats:sub>181<\/jats:sub> CSF levels was observed in chronic pain patients with negative amyloid and neurodegeneration markers. Amyloid\u2010positive and neurodegeneration\u2010negative chronic pain patients showed higher memory function cross\u2010sectionally. No significant longitudinal decline in cognitive function was observed for any ATN group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our study suggests that chronic pain induces neuronal damage and microglial activation in particular subgroups of patients along the AD spectrum. Further studies are needed to confirm these findings. 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