In a study published in Nature Mental Health, scientists from China and the United States have discovered that people suffering from CMP may face an increased risk of brain aging.
Morphological and Genetic Decoding Shows Heterogeneous Patterns of Brain Aging in Chronic Musculoskeletal Pain
CMP, a prevalent and heterogeneous condition characterized by persistent pain in various parts of the body, is one of the leading causes of disability worldwide and greatly affects the brain. In addition to experiencing pain, older adults with CMP also have accelerated cognitive decline and a higher risk of dementia, with a limited understanding of the biological mechanisms underlying the associations between CMP and dementia risk.
A multiscale study to separate pathological brain aging from normal brain aging can reveal the underlying mechanisms. Using large-scale cross-sectional and longitudinal cohorts (N = 9,344), we developed a brain age model based on MRI (N = 6,725) to assess the difference between brain age and chronological age, termed "predicted age difference" (PAD), in various common types of CMP (N = 2,427).
Our study reveals a significant increase in the PAD in cohorts with knee osteoarthritis (KOA) compared to healthy controls, and we validated this in an independent dataset (N = 192), suggesting a pattern of brain aging acceleration in KOA. This acceleration was driven by the hippocampus in both datasets and predicted memory decline and incidents of dementia during follow-up.
The SLC39A8 gene showed pleiotropy between brain aging accelerations and KOA and exhibited spatial transcriptional associations with regional contributions to brain aging accelerations. Genes showing strong spatial transcriptional associations with regional contributions were highly expressed in microglial cells and astrocytes, and were mainly enriched in synaptic structure and neurodevelopment.
These findings highlight a heterogeneous pattern of brain aging in CMP and reveal a hereditary morphological pattern linking brain aging acceleration to cognitive decline and an elevated risk of dementia in KOA.
CMP is a leading cause of disability, affecting more than 40% of the global population, and impacts patients´ cognitive function. Although the exact mechanism is not fully understood, which hinders prevention and treatment efforts, research indicates that inflammatory markers associated with brain aging are higher in CMP patients, suggesting a link between brain aging and CMP.
In light of this finding, researchers led by Prof. TU Yiheng from the Institute of Psychology at the Chinese Academy of Sciences, in collaboration with international experts, explored brain aging patterns and underlying mechanisms in different types of CMP. Their study highlights the association between chronic knee pain, particularly due to KOA, and accelerated brain aging.
Using structural MRI data from over 9,000 individuals, the researchers developed a brain age model to compare brain age with chronological age. They found that individuals with KOA, identified in both the UK Biobank and additional local community replication datasets, experienced faster brain aging than healthy individuals. Additionally, brain regions responsible for cognitive function, such as the hippocampus, were associated with this accelerated brain aging.
"Not only did we reveal the specificity of accelerated brain aging in patients with KOA, but more importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk," said Professor TU, corresponding author of the study.
Moreover, the researchers delved into the genetic landscape and identified the SLC39A8 gene as a shared link between KOA and accelerated brain aging. This gene, particularly expressed in microglial cells and astrocytes, underscores the potential role of inflammation and neurodevelopment in the observed phenomena.
This study not only provides compelling evidence of KOA´s neurocognitive impacts but also opens new avenues for early detection and intervention strategies targeting dementia risk factors.
The collaboration between multidisciplinary teams from China and the United States underscores the global effort to understand and address the intertwined challenges of aging, chronic pain, and cognitive decline.
