Mass General Brigham Neuroscience Institute researchers have found that a pattern of brain atrophy visible on MRI could help predict how quickly people with early-onset Alzheimer’s disease progress from mild cognitive impairment to dementia. This could help patients, families, and clinicians know what to expect and plan future caregiving and living arrangements. Results are published in Neurology ®, an official journal of the American Academy of Neurology .
Early-onset Alzheimer’s disease is a rare type of Alzheimer’s disease that begins before age 65. Although early-onset Alzheimer’s progresses faster on average than later-onset Alzheimer’s, progression varies substantially from person to person, making prognosis difficult.
“Early-onset Alzheimer’s disease is a challenging diagnosis, worsened by the fact that patients, their caregivers and clinicians don’t know what to expect in the years after the diagnosis,” said co-senior author Alexandra Touroutoglou, PhD, an investigator with the Mass General Brigham Neuroscience Institute. “If we can use an MRI that is already part of the diagnostic process to better estimate how quickly someone’s disease may progress, we could help patients and families plan ahead and help clinicians make more personalized decisions about care.”
Researchers analyzed data from 130 people between the ages of 40 and 64 with mild cognitive impairment due to early-onset Alzheimer’s disease and 97 cognitively normal age-matched controls from the Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS), a United States multi-center consortium that is the largest study of early-onset Alzheimer’s disease globally.
During an average follow-up of approximately two years, 84 of the participants with early-onset Alzheimer’s disease, or about 65%, progressed from mild cognitive impairment to dementia, the term used to describe when loss of memory, language, problem solving or other thinking abilities interfere with daily life. Looking at MRI scans taken at the beginning of the study, researchers found that people who had greater shrinkage in parts of the brain responsible for memory and thinking were more likely to develop dementia sooner than those with less shrinkage. As brain atrophy increased, the risk of progressing to dementia rose.
“This study may pave the way to using quantitative measures of brain atrophy in vulnerable brain regions as a way of predicting the timing of functional decline. This is information we haven’t yet been able to give to patients,” said co-senior author Mark Eldaief, MD, a neurologist in the Memory Disorders and Frontotemporal Dementia Units with the Mass General Brigham Neuroscience Institute.
Adding the MRI measure improved the fit of a model that predicted dementia risk based on age, sex, and performance on a baseline cognitive test.
The researchers note that the model was developed and tested in people who predominantly had memory-related mild cognitive impairment, meaning the findings may not apply as well to people whose early-onset Alzheimer’s disease primarily affects behavior, vision and spatial skills, or language. Additional studies are needed to validate the MRI measure in diverse populations and determine whether it predicts meaningful outcomes such as institutionalization or mortality. Future studies could also combine MRI with tau and amyloid measures to help clinicians identify patients who are likely to need closer monitoring and earlier care planning.
Authorship: In addition to Touroutoglou, Mass General Brigham authors include Thiago Paranhos, Yuta Katsumi, Michael Brickhouse, Ani Eloyan, Ryan Eckbo, Alexander Zaitsev, Anna Du, and co-senior authors Bradford C. Dickerson and Mark C. Eldaief. Additional authors include Renaud La Joie, Maryanne Thangarajah, Alexander Taurone, Prashanthi Vemuri, Clifford R. Jack Jr., Dustin B. Hammers, Paul Aisen, Laurel Beckett, Robert Koeppe, Walter A. Kukull, Arthur Toga, Alireza Atri, David Glenn Clark, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Ian M. Grant, Lawrence S. Honig, Erik Johnson, David T. Jones, Joseph C. Masdeu, Mario F. Mendez, Erik S. Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, Stephen Salloway, Sharon J. Sha, Raymond Scott Turner, Thomas S. Wingo, David A. Wolk, Kyle B. Womack, Maria C. Carrillo, Gil Dan Rabinovici and Liana G. Apostolova.
Disclosures: None.
Funding: This study was supported by the National Institute on Aging (R56 AG057195, U01AG6057195, U24AG021886) and the Alzheimer’s Association (LEADS GENETICS-19-639372, LDRFP-21-818464, LDRFP-21-824473, LDRFP-21-828356).
Paper cited: Paranhos T et al. “EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease: An MRI-Based Prognostic Biomarker” Neurology DOI: 10.1212/WNL.0000000000218519
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EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease: An MRI-Based Prognostic Biomarker
26-Aug-2026