Brain shrinkage biomarker may predict early-onset Alzheimer’s progression

In people diagnosed with early-onset Alzheimer's disease, a biomarker tool that detects shrinkage of the brain's gray matter may predict how quickly someone may progress from mild cognitive impairment (MCI) to dementia, according to a new study published August 26, 2026, in Neurology^®, an official journal of the American Academy of Neurology.

Early-onset Alzheimer's disease develops before age 65, while people are still working or raising families. It begins with mild cognitive impairment, thinking and memory problems that are greater than normal aging but not severe enough to be diagnosed as dementia. It often progresses quickly to dementia, but the timeline varies widely from person to person.

This is a study driven by one of the most frequent questions we get from patients in the clinic: 'When will I lose my independence? There are limited ways to predict the transition from MCI to dementia, so we developed a brain scan biomarker called the early-onset Alzheimer's disease signature, a map that can be applied to brain scans to measure shrinkage in regions of the brain involved in thinking such as memory, language and reasoning. Our study found that brain shrinkage measured by our biomarker can act as a timer for predicting when dementia will start and how quickly someone progressed from MCI to dementia."

Alexandra Touroutoglou, PhD, study author, Harvard Medical School, Boston, Massachusetts

The early-onset Alzheimer's disease signature biomarker includes a set of brain regions that show greater atrophy in people with the disease than in people without the disease.

The study included data from 130 people who lived independently with mild cognitive impairment and 97 healthy participants. They were all between ages 40 and 64. Participants had magnetic resonance imaging brain scans at the start of the study and at least one annual follow-up visit.

Researchers applied the brain scan biomarker to each participant's brain scan to measure shrinkage in eight key brain areas involved in thinking and memory, including the medial and lateral parietal cortex as well as the posterior lateral temporal cortex.

They calculated average thickness of each brain region and then combined those measurements into an overall score for brain shrinkage.

Participants were followed for an average of two years. Approximately 65% of people with early-onset Alzheimer's disease progressed from MCI to dementia.

Researchers found that greater gray matter shrinkage on brain scans as detected by the biomarker predicted faster progression to dementia. A person's risk of progression from MCI to dementia was 1.24 times higher for every one standard deviation greater magnitude of shrinkage.

The biomarker was better at predicting progression than looking only at people's symptoms at the beginning of the study.

"Better tools are needed to predict when someone with early-onset Alzheimer's disease may lose independence and progress from MCI to dementia," said Touroutoglou. "This brain scan biomarker we developed may help predict how quickly the disease will progress in each individual, giving physicians, people with early-onset Alzheimer's disease and their families better information about what to expect and allowing earlier clinical trial enrollment for treatments that may improve outcomes."

A limitation of the study was that the brain scan biomarker was developed and tested in one group, most of whom were non-Hispanic white people, so it is unclear how well it may work when applied to other populations.

The study was supported by the National Institutes of Health and the Alzheimer's Association.