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A study in PLOS Medicine analyzed brain MRI data from 45,900 controls and 2,698 people with various conditions. Alzheimer’s disease and mild cognitive impairment had the strongest associations with higher estimated brain age; addiction and some psychiatric disorders were also associated with higher estimates. The findings are correlational and do not show that the conditions cause faster brain aging.
A study published in PLOS Medicine reports that people with Alzheimer’s disease, mild cognitive impairment, addiction and some psychiatric disorders tend to have higher MRI-based estimates of brain age than expected for their chronological age. The analysis found the strongest associations for Alzheimer’s disease and mild cognitive impairment, but it does not establish that these conditions cause accelerated aging.
Led by Shile Qi of Nanjing University of Aeronautics and Astronautics in China, the researchers analyzed structural MRI scans from 45,900 controls drawn from several imaging databases and compared them with scans from 2,698 people with a range of conditions. Those included Alzheimer’s disease, mild cognitive impairment, schizophrenia, bipolar disorder, major depressive disorder, alcohol or tobacco addiction, ADHD and autism spectrum disorder.
The team used predictive age difference, or PAD, a measure comparing a person’s chronological age with an age estimated from brain imaging. A positive PAD indicates that the brain appears older than typical for that age. Alzheimer’s disease and mild cognitive impairment showed the strongest associations with higher PAD; addiction and psychiatric disorders were also associated with elevated values. The study found no overall PAD difference between controls and people with ADHD or autism.
The researchers also examined differences across brain regions. Higher PAD in the prefrontal cortex appeared across multiple disorders. Psychiatric conditions were associated with elevated estimates in frontal and temporal regions, while dementia was linked to higher PAD in frontal and occipital areas. Addiction showed a different distribution, including the default mode and salience networks, the putamen and the thalamus. The team reported gene-expression differences associated with some conditions, which may point to distinct biological processes, though the analysis does not establish a mechanism.
How Brain Age Patterns Could Help Research
The findings suggest that an MRI-based aging measure may capture different patterns across conditions, rather than one common signature for every disorder. That distinction could help researchers investigate whether brain-age estimates are useful for studying disease-related changes or identifying candidate biomarkers.
For patients and families, the results are not a diagnostic test or a prediction of an individual’s future. A higher PAD is a group-level association in this study; it does not show that a particular person’s brain is aging faster, nor does it establish what caused a difference. The research may guide further study, but it does not support changing treatment or making health decisions based on a brain-age estimate.
MRI brain scan for cognitive health
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How Researchers Estimate Brain Age
Brain-age studies use imaging data and statistical models to estimate age from features of the brain. Researchers compare that estimate with a person’s actual age to calculate predictive age difference. A positive difference means the model estimates an older brain; it is not the same as a clinical diagnosis of dementia or another disorder.
In this report, investigators drew control scans from several databases and compared them with data from people with multiple neurological, psychiatric and substance-use conditions. The range allowed the team to examine both overall PAD and regional patterns. The study was supported by research funding from Jiangsu Province and the National Natural Science Foundation of China; the report says funders had no role in study design, data collection and analysis, publication decisions or manuscript preparation.
“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.”
— The study authors
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Limits of the Brain Age Findings
The study is correlational, so it cannot show that a disorder directly causes a higher brain-age estimate. The report also notes that psychiatric conditions and addiction often occur together, making it difficult to separate their individual associations. The available summary does not specify whether all potential influences on brain structure were accounted for or how well the findings would apply to people outside the datasets analyzed.
It is also unclear whether PAD can reliably track changes within an individual over time or predict symptoms, disease progression or response to treatment. The reported gene-expression patterns suggest possible biological links, but they do not prove that a particular gene process produces the observed MRI differences. Further studies would be needed to test those possibilities and determine whether PAD has clinical use.
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Testing the Measure in Future Studies
The next step is independent research to test whether the reported patterns can be reproduced in other populations and datasets. Studies that follow participants over time could examine whether PAD changes alongside symptoms or disease progression, and whether regional patterns help distinguish overlapping conditions.
Researchers would also need to assess whether brain-age estimates add useful information beyond existing clinical assessments before proposing them as biomarkers for care. The current report identifies associations and research questions; it does not announce a clinical tool or a change to diagnostic practice.
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Key Questions
Which conditions had the strongest links to higher brain-age estimates?
Alzheimer’s disease and mild cognitive impairment showed the strongest associations with higher predictive age difference in the study. Addiction and some psychiatric disorders were also associated with higher estimates.
Did the study find higher brain age for ADHD or autism?
The researchers found no overall PAD difference between controls and people with ADHD or autism spectrum disorder. That result concerns this study’s overall measure and does not rule out other brain differences.
Does a higher brain-age estimate mean a disorder caused faster aging?
No. The study was observational and correlational. It found associations but cannot establish whether a condition causes a higher estimate or whether other factors contribute.
Can brain-age scans diagnose dementia or predict an individual’s future?
The report does not establish PAD as a diagnostic or prediction tool. The findings describe group-level patterns, and further research would be needed to determine whether the measure can support clinical decisions.
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