How researchers measure brain aging

Researchers can estimate whether a person’s brain appears older or younger than expected based on their chronological age. One method uses predicted age difference (PAD), which compares a person’s actual age with the age estimated from brain imaging.

A positive PAD value means that a person’s brain appears older than would normally be expected for their chronological age. Higher PAD values may therefore indicate signs of accelerated brain aging.

Study analyzed brain scans from more than 48,000 people

To investigate how different brain conditions affect PAD, the researchers analyzed structural magnetic resonance imaging (MRI) data from 45,900 control participants drawn from several brain-imaging databases.

They compared these 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 and major depressive disorder.

Alzheimer’s disease and mild cognitive impairment show the strongest link

Among the conditions studied, the neurodegenerative disorders Alzheimer’s disease and mild cognitive impairment showed the strongest association with higher PAD values. This suggests that these conditions are linked to the most pronounced signs of accelerated brain aging.

Addiction and psychiatric disorders were also associated with increased PAD. However, the researchers found no overall difference in PAD between control participants and people with ADHD or autism spectrum disorder.

Different conditions affect different brain regions

The research team also examined PAD in individual brain regions and investigated patterns of gene expression associated with different conditions.

The prefrontal cortex stood out because it showed high PAD across multiple brain disorders. Psychiatric illness was associated with increased PAD in the frontal and temporal lobes, while dementia was associated with increased PAD in the frontal and occipital lobes.

Addiction showed a different pattern. Higher PAD was observed in the default mode network, the salience network, the putamen and the thalamus.

The researchers also identified differences in gene transcription associated with specific conditions or divergences. These findings suggest that distinct patterns of brain aging may be connected to different underlying biological processes.

Could brain-age patterns lead to new biomarkers?

The study does not show that these conditions directly cause accelerated brain aging. The research was correlational, and some conditions—particularly mental disorders and addictions—frequently occur together. This can make it difficult to separate the effects of each condition.

Nevertheless, the researchers suggest that closer study of predicted age difference could eventually help identify biomarkers associated with common brain diseases and provide new clues about the biological pathways involved.

The authors added, “Different neurological diseases appear to leave different imprints on the brain’s aging clock, and this could help researchers better understand the neural and biological pathways involved in these diseases.”

This study was supported by the Key Research and Development Program of Jiangsu Province of China (BE2023668) to SQ and the National Natural Science Foundation of China (62376124) to SQ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.