People with dementia, mild cognitive impairment, alcohol addiction, and psychiatric conditions such as schizophrenia may show signs of accelerated brain aging, according to a study published in the open access journal PLOS Medicine. The research, led by Shile Qi of the Nanjing University of Aeronautics and Astronautics, China, found that different conditions appear to be associated with distinct patterns of aging across the brain.
Researchers can estimate whether a person’s brain appears older or younger than expected for their chronological age. One way to do this is with predictive age difference (PAD), which compares a person’s actual age with an age estimated from brain imaging. A positive PAD means the brain appears older than would typically be expected.
To investigate how different brain conditions might influence this measure, the researchers analyzed structural magnetic resonance imaging (MRI) data from 45,900 controls drawn from several brain imaging databases. They compared those scans with data from 2,698 people with a range of conditions and differences, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), alcohol or tobacco addiction, Alzheimer’s disease (AD), mild cognitive impairment (MCI), schizophrenia, bipolar disorder or major depressive disorder.
Alzheimer’s and MCI Show the Strongest Associations
Among the conditions examined, the neurodegenerative disorders AD and MCI showed the strongest associations with higher PAD values, suggesting the greatest degree of accelerated brain aging.
Addiction and psychiatric disorders were also associated with increased PAD. By contrast, the researchers found no overall differences in PAD between controls and people with ADHD or ASD.
Different Disorders Affect Different Brain Regions
The team also examined PAD across individual brain regions and looked at patterns of gene expression associated with the different conditions.
One area that stood out was the prefrontal cortex, which showed higher PAD across multiple brain disorders. Psychiatric disorders were associated with elevated PAD in the frontal and temporal lobes, while dementia was linked to higher PAD in the frontal and occipital cortex.
Addiction showed a different pattern. Higher PAD was observed in the default mode network, as well as in the salience network, putamen and thalamus.
The researchers also identified differences in gene transcription associated with particular conditions and divergences, suggesting that the patterns of brain aging may be linked to distinct underlying biological processes.
A Potential Source of Future Biomarkers
The findings do not show that these conditions directly cause accelerated brain aging. The study is correlational, and some conditions, particularly psychiatric disorders and addiction, frequently occur together, which can make their individual effects difficult to separate.
Even so, the researchers suggest that studying PAD more closely could eventually help identify biomarkers associated with common brain disorders and provide new clues about the biological pathways involved.
The authors add, “Different neurological disorders appear to leave different signatures on the brain aging clock, which may help researchers better understand the neural and biological pathways involved in these conditions.”
This work was supported by the Key Research and Development Plan of Jiangsu Province, China (BE2023668) to S.Q., and the National Natural Science Foundation of China (62376124) to S.Q. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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