Abstract
INTRODUCTION
Early-onset and late-onset Alzheimer’s disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head-to-head comparison of cortical atrophy in EOAD and LOAD, using two large and well-characterized cohorts (LEADS and ADNI).
METHODS
We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early-stage AD), along with cognitively unimpaired participants.
RESULTS
After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD.
DISCUSSION
Our findings point to the clinical utility of MRI-based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment.
Highlights
Early-onset Alzheimer’s disease (EOAD) and late-onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns.
EOAD patients showed prominent atrophy in widespread neocortical regions.
LOAD patients showed prominent atrophy in the anterior medial temporal lobe.
Regional atrophy was correlated with the severity of global cognitive impairment.
Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.
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Alexandra Touroutoglou,
Michael Brickhouse,
Ani Eloyan,
Ryan Eckbo,
Alexander Zaitsev,
Renaud La Joie,
Julien Lagarde,
Daniel Schonhaut,
Maryanne Thangarajah,
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Mario F. Mendez,
Erik Musiek,
Chiadi U. Onyike,
Meghan Riddle,
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Stephen Salloway,
Sharon Sha,
R. Scott Turner,
Thomas S. Wingo,
David A. Wolk,
Kyle Womack,
Maria C. Carrillo,
Gil D. Rabinovici,
Liana G. Apostolova,
Bradford C. Dickerson,
the LEADS Consortium for the Alzheimer’s Disease Neuroimaging Initiative | February 19, 2025