Morphological and genetic decoding show heterogenous patterns of brain aging in chronic musculoskele
Poster No:
2506
Submission Type:
Abstract Submission
Authors:
Lei Zhao1, Yiheng Tu1
Institutions:
1Institute of Psychology of the Chinese Academy of Sciences, Beijing, Beijing
First Author:
Co-Author:
Introduction:
Patients with chronic pain (CP) are at a higher risk of dementia, but the mechanism remains unclear. Dementia-risk-related biological impairments in the brain accumulate with age but vary in velocity across different conditions, suggesting the implication to decode the neurobiological mechanisms between CP and dementia via characterizing brain aging. Considering CP is a unifying symptom in a series of highly heterogeneous conditions, whether common CP types present a general or distinct brain aging patterns that are associated with patients' cognitive functions, dementia risks, and genetic predisposition, are still unknown.
Methods:
To decode accelerated brain aging in CP, we developed an MRI-based brain age model in healthy adults (N = 6,725) and applied it to examine the brain aging acceleration (quantified by the predicted age difference [PAD]) in five common types of CP (Dataset 1; N = 2734) including knee pain, back pain, headache, neck pain, and hip pain. The findings of brain aging acceleration were further validated in an independent dataset (Dataset 2; N = 192) that had baseline and 5-year follow-up sessions. The associations between brain aging acceleration and pain symptoms, cognitive function, and dementia risks were assessed cross-sectionally and longitudinally. We also employed genetically pleiotropic, imaging-transcriptomic and enrichment analyses to identify the molecular genetic basis of brain aging acceleration in CP.
·flow chart
Results:
Compared to healthy controls, a significantly increased PAD was only observed in chronic knee pain cohort (Cohen's d = 0.130). In the subgroups of chronic knee pain, a significant increase in PAD was found in the knee osteoarthritis (KOA) cohort (d = 0.437) but not in the subgroup without KOA. The increased PAD in KOA was replicated in Dataset 2 (d = 0.454) and was associated with memory decline (r = 0.348) and dementia risk (Spearman's rho = 0.278). The gene SLC39A8 showed pleiotropy between brain aging acceleration and KOA, as well as transcriptional associations with KOA neuroimaging phenotypes across both datasets. The genes exhibiting transcriptional associations with KOA neuroimaging phenotypes were highly expressed in microglial cells and astrocytes, and primarily enriched in synaptic structure and neurodevelopment.
·Main Results
Conclusions:
In summary, our study demonstrates the heterogeneity of brain aging in CP and unfolded a distinct heritable pattern that links KOA to dementia by providing an integrative biological profile that connects specific genes, molecular processes, and cell classes with morphological brain aging.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Lifespan Development:
Aging 2
Modeling and Analysis Methods:
Multivariate Approaches
Novel Imaging Acquisition Methods:
Anatomical MRI
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Keywords:
Aging
Cognition
MRI
Multivariate
Pain
1|2Indicates the priority used for review
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