Association of chronic pain with biomarkers of neurodegeneration, microglial activation and inflammation in the CSF and impaired cognitive function

<jats:sec><jats:title>Objectives</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 (ADNI).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Participants were classified using the ATN classification. Chronic pain was defined as persistent or recurrent pain reported at baseline. For each ATN group, ANCOVA models identified differences in CSF levels of Aβ<jats:sub>1‐42</jats:sub>, ptau181, t‐tau, sTREM2 and cognitive function between chronic pain states. Differences in CSF levels of inflammatory markers between chronic pain states were further analysed. 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‐Alzheimer's pathophysiology (SNAP) and chronic pain showed increased CSF levels of t‐tau and sTREM2. Chronic pain was associated with increased TNF‐α 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 positive and neurodegeneration negative chronic pain patients showed higher memory function cross‐sectionally. 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 those findings.</jats:p><jats:p>This article is protected by copyright. All rights reserved.</jats:p></jats:sec>