Brain Shrinkage Could Act as a 'Timer' for Early-Onset Dementia

A brain scanning method that quantifies shrinkage in regions responsible for cognitive function may assist in forecasting how rapidly individuals with early-onset Alzheimer's disease advance from mild cognitive impairment to dementia, a research study proposes. Early-onset Alzheimer's disease manifests before the age of 65, frequently commencing with mild cognitive impairment (MCI), characterized by noticeable yet not severe memory and thinking issues.

Progression from MCI to dementia varies significantly among individuals. Researchers aimed to ascertain whether specific patterns of brain atrophy could predict the probable speed of this progression. They developed a brain scanning tool, termed the early-onset Alzheimer's disease signature, which identifies atrophy or shrinkage in particular areas of the brain's gray matter, focusing on eight regions related to cognition and memory, encompassing segments of the parietal cortex and temporal cortex.

Utilizing MRI scans, researchers assessed the thickness of these regions and amalgamated the findings into a single score signifying the extent of brain shrinkage. The study encompassed 130 individuals with mild cognitive impairment who were residing independently and 97 healthy controls, all aged between 40 and 64 years. Each participant underwent an MRI scan at the study's outset and engaged in at least one annual follow-up visit, with an average follow-up duration of two years.

During the study period, approximately 65 percent of those with early-onset Alzheimer's disease progressed from MCI to dementia. Researchers discovered that greater gray matter atrophy was correlated with faster progression. For each standard deviation increase in the level of atrophy, the risk of transitioning from MCI to dementia was 1.24 times greater.

The brain scan biomarker also proved more effective in predicting progression than merely evaluating a person's symptoms at the study's initiation. Lead researcher Alexandra Touroutoglou from Harvard Medical School stated that one of the most frequent inquiries patients pose is: "When will I lose my independence?" The researchers highlighted that current methods for predicting when someone with early-onset Alzheimer's disease will transition from MCI to dementia are limited.

Their findings indicate that the biomarker could function as a "timer" or "clock," enabling physicians to estimate when dementia might commence and how swiftly the disease could progress. Dr. Ronald Schwartz, senior director of Continuum Health Services at Masonicare, commented to Newsweek that such a tool could be "extraordinarily valuable."

He asserted: "One of the most challenging aspects of early-onset Alzheimer's disease is that we know the disease is progressive, but we cannot accurately inform an individual patient or family how swiftly that progression will occur. Early-onset disease also exhibits considerable clinical variability, making a one-size-fits-all prediction particularly challenging."

The study suggests that the tool could aid patients and families in understanding what to anticipate in the future and signal when individuals may benefit from participating in clinical trials for potential treatments. Schwartz emphasized that a more reliable forecasting tool could enable physicians to provide more meaningful expectations, support care planning, and assist families in making decisions regarding work, finances, and future support requirements.

However, he stressed that any prediction tool should be employed to enhance conversations rather than function as a "crystal ball." The biomarker essentially constitutes a map of brain regions that tend to shrink more in individuals with early-onset Alzheimer's disease than in those without it. Researchers can leverage this map on MRI scans, measure the degree of shrinkage, and utilize the outcome to estimate the likely speed of progression.

Nevertheless, the researchers noted that the biomarker was developed and validated within a single study group, and most participants were non-Hispanic White. Consequently, it remains uncertain whether it would be equally effective across diverse populations. Schwartz mentioned that additional questions would need to be addressed before a tool like this could be widely implemented in clinical practice.

Among these, he stated that researchers would need to demonstrate the tool's accuracy in predicting outcomes for individual patients across various ages, disease stages, and clinical presentations, and whether providing such predictions ultimately improves care and decision-making for patients and families. While the findings suggest that measuring gray matter shrinkage via MRI scans may help doctors, patients, and families better comprehend what to expect, the tool necessitates further testing on a broader scale.

Paranhos, T., et al. (2026). EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease. Neurology. DOI: 10.1212/WNL.0000000000218519. https://www.neurology.org/doi/10.1212/WNL.0000000000218519. Contact Newsweek editors regarding this story: Kara Dolman and Emma Lee-Sang.