Nearly 49,000 brain scans reveal aging signatures linked to dementia, addiction and mental illness

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Illustration depicting a brain aging clock. Credit: Shile Qi and Chuang Liang (CC-BY 4.0, creativecommons.org/licenses/by/4.0/)

People with dementia, mild cognitive impairment, alcohol addiction or psychiatric disorders such as schizophrenia show increased brain aging, each in specific patterns within the brain, according to a study published in PLOS Medicine by Shile Qi from the Nanjing University of Aeronautics and Astronautics, China, and colleagues.

Some conditions can make the brain age faster. Scientists calculate how old the brain is relative to the body using the predictive age difference (PAD), the difference between chronological age and the age predicted by brain imaging, where a positive PAD indicates that aging is accentuated or increased.

To better understand how brain disorders and differences might affect brain aging, the authors of this study collected structural magnetic resonance imaging (MRI) data from 45,900 controls across several brain imaging banks and compared them with 2,698 patients with different brain 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.

Where the strongest effects appeared

The authors found that the neurodegenerative conditions AD and MCI had the largest association with higher PAD. Addiction and psychiatric disorders were also associated with increased PAD. In contrast, there were no differences in PAD between people with ADHD or ASD and controls.

The researchers also looked at PAD values in specific areas of the brain and examined which genes showed increased expression in people with different brain conditions. The prefrontal cortex showed higher PAD across brain disorders.

Distinct patterns across the brain

Higher PAD in the frontal and temporal lobes was associated with psychiatric disorders, while higher PAD in the frontal and occipital cortex was associated with dementia. Addiction was connected with higher PAD in the default mode network, salience network, putamen and thalamus.

There were also differences in gene transcription that were associated with specific conditions and differences. While the results are correlational, not causal, and while some conditions such as psychiatric disorders and addiction have high co-occurrence, the authors suggest that understanding more about PAD could help provide biomarkers for commonly occurring brain disorders.

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."

Publication details

Liang C, et al. Brain aging patterns among nine neurological disorders: A case-control study. PLOS Medicine (2026). DOI: 10.1371/journal.pmed.1004860

Journal information: PLoS Medicine

Key medical concepts

Alzheimer's DiseaseDementiaSchizophrenia

Clinical categories

NeurologyPsychiatryHealthy agingPsychology & Mental health Provided by Public Library of Science Who's behind this story?

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