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

## TL;DR

Chronic pain is linked to brain changes similar to those seen in Alzheimer's, suggesting a need for better research to understand its impact on brain health and dementia risk.

## Contribution

This systematic review comprehensively maps brain health alterations in chronic pain and highlights overlaps with neurodegenerative biomarkers.

## Key findings

- Chronic pain is associated with reduced grey matter and weaker white matter, resembling Alzheimer's disease patterns.
- MRI studies show chronic pain patients have signs of accelerated brain aging, including older brain age and higher white matter hyperintensities.
- Changes in brain activity and chemical levels, such as increased brain-derived neurotrophic factor, were observed in chronic pain patients.

## Abstract

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.

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.

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.

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.

We reviewed all studies written in English on adults with long‐term (chronic) pain and brain health. We searched two large databases up to 1 November 2024. Studies had to compare people with chronic pain to people without pain. We collected their results and checked each study for quality. Some research has shown that people with chronic pain have a higher chance of a dementia diagnosis in later life. We do not fully know how chronic pain links to brain changes or to faster brain ageing. By bringing many studies together, we aimed to map the main brain changes linked to chronic pain to improve care and find targets for treatment. We found 365 suitable studies to compare. Most were small studies done at a single time point in middle‐aged adults, often from China or the United States, and many had moderate to high risk of being unfair (biased) because of the way the studies were done. Magnetic resonance imaging (MRI) brain scans were the most common way to measure brain health. On MRI scans, people with chronic pain often had patterns that were like the patterns seen in people with Alzheimer's disease: less grey brain tissue, weaker white brain tissue, and signs of older brain age in places such as the hippocampus (the memory centre of the brain). There were also changes in brain chemical levels and brain activity levels in people with chronic pain compared to those without chronic pain. The findings suggest wide brain changes in people with chronic pain. Larger, better‐designed studies are needed to understand these links more clearly.