Your Brain Might Be Older Than You Think – And It Could Explain Memory Loss

Using machine learning and brain scans, researchers found that accelerated brain aging increases the impact of cognitive risk factors on memory and thinking, particularly in people with cerebrovascular disease.

The difference between a person’s predicted brain age and their actual age, known as the brain age gap, may affect how cognitive impairment risk factors, such as high blood pressure and diabetes, relate to thinking and memory skills, according to a study in Neurology, the medical journal of the American Academy of Neurology.

Recent advances in neuroimaging have enabled the use of machine learning tools trained on brain scans to identify variations in brain aging and estimate a brain’s biological age.

“As we get older, our brains change, with less brain volume and fewer blood vessels that support brain tissue, and diseases can worsen these changes, profoundly affecting brain health,” said study author Saima Hilal, MD, PhD, of the National University of Singapore. “Such signs of brain aging can be seen on brain scans, showing if a person’s brain looks older than their actual age. Our study found that having more risk factors for cognitive impairment is associated with poorer cognitive performance, with the brain age gap playing a key role in this connection. This effect was more noticeable in people with cerebrovascular disease.”

Study details and participant profiles

The study included 1,437 participants without dementia, with an average age of 66. Among them, 60% showed no signs of cognitive impairment.

Researchers collected participants’ medical histories through questionnaires, interviews, and a review of medications. Each person also underwent physical exams, lab tests, and brain scans.

To assess the risk of cognitive impairment, researchers assigned each participant a score based on several factors: age, ethnicity, education, past and current smoking habits, body mass index, symptoms of depression, high blood pressure, diabetes, high cholesterol, and history of stroke. Higher scores reflected a greater risk of cognitive impairment.

Measuring cognitive risk and thinking skills

To assess thinking and memory skills, also known as cognitive performance, participants completed tests that measured executive function, attention, language, memory, visuoconstruction—which involves the ability to copy a drawing or build a model—and visuomotor speed, which refers to how quickly a person can process visual information and respond with movement.

Researchers found higher cognitive impairment risk factor scores were consistently associated with poorer cognitive performance, especially for visuoconstruction and visuomotor speed.

Brain age prediction using machine learning

Using machine learning, researchers developed a brain age prediction model to review participants’ brain scans and determine the predicted biological brain age of each participant. Researchers then subtracted a person’s chronological brain age from their predicted brain age to calculate their brain age gap. A positive brain age gap implied accelerated brain aging.

Researchers also used brain scans to look for markers of cerebrovascular disease, such as microbleeds and infarcts, areas of dead tissue due to lack of blood supply. They compared people with high and low amounts of markers.

Researchers found in people with a high amount of these cerebrovascular disease markers, the brain age gap influenced how cognitive impairment risk factors affected thinking and memory skills, especially in areas like executive function and language.

They found the proportion of mediation, or how much the relationship between cognitive impairment risk factors and thinking memory skills was affected by the brain age gap, was 20% overall, 34% for executive function, and 27% for language.

“The brain age gap may be a helpful biomarker in determining a person’s risk of cognitive decline,” said Hilal. “Our findings suggest that accelerated brain aging may serve as an important factor linking cognitive impairment risk factors to thinking and memory skills in adults with cerebrovascular conditions.”

A limitation of the study was that it looked only at Southeast Asian people, so the results may not be the same for other populations. Researchers were also unable to examine the effects of exercise, diet, and genetic markers for Alzheimer’s disease on brain structure and cognition because data were not available for all participants.

Reference: “Role of Brain Age Gap as a Mediator in the Relationship Between Cognitive Impairment Risk Factors and Cognition” by Wei Ying Tan, Xiangyuan Huang, Jiannan Huang, Caroline Robert, Jiangbo Cui, Christopher P.L.H. Chen and Saima Hilal, 18 June 2025, Neurology.
DOI: 10.1212/WNL.0000000000213815

The study was supported by the National University of Singapore, the Singapore National Medical Research Council and the Singapore Ministry of Education.

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