A systematic review of brain health in adults with chronic pain.

INTRODUCTION: Recent research has linked chronic pain with an increased risk of clinical dementia diagnosis. Yet structural and functional brain changes associated with chronic pain and their potential role in accelerating brain ageing have not been characterised comprehensively. Understanding these effects is crucial to developing targeted prevention and management strategies. METHODS: We conducted a systematic review of all English language articles in MEDLINE and Embase. Studies were eligible if they compared neuroimaging, clinical, biological, cognitive or mental health outcomes in adults with chronic pain to healthy controls. Following screening, data were extracted and the risk of bias was assessed. RESULTS: Of 5805 identified studies, 365 met the inclusion criteria. Most were cross-sectional studies with small sample sizes; conducted in middle-aged populations in China or the USA; had moderate to high risk of bias; and represented > 30 distinct pain phenotypes. Magnetic resonance imaging was the most common method for assessing brain health. Key findings in patients with chronic pain included: lower grey matter volumes and reduced fractional anisotropy; evidence of accelerated brain ageing including older brain age and higher white matter hyperintensities; mixed results in resting state functional connectivity; increased power densities and connectivity on electroencephalography; and higher levels of serum brain-derived neurotrophic factor. The most consistently affected brain regions across magnetic resonance imaging studies were the insula; anterior and posterior cingulate; thalamus; hippocampus; primary motor cortex; and cerebellum. DISCUSSION: Adults with chronic pain exhibit widespread alterations in brain health compared with healthy controls. Several observed features overlap with biomarkers of Alzheimer's disease and other forms of neurodegeneration. These findings highlight the need for larger, well-designed studies incorporating clearly defined pain phenotypes, multimodal imaging and causal inference methods to clarify the role of chronic pain in brain ageing and dementia risk.