We compared white matter hyperintensities (WMHs) in early-onset Alzheimer’s disease (EOAD) with cognitively normal (CN) and early-onset amyloid-negative cognitively impaired (EOnonAD) groups in the Longitudinal Early-Onset Alzheimer’s Disease Study.
We investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t-tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden.
EOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group.
EOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD.

This study represents a comprehensive characterization of WMHs in sporadic EOAD.
WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD.
Greater WMH volumes are associated with worse performance on global cognitive tests.
EOAD participants have higher WMH volumes compared with CN and early-onset amyloid-negative cognitively impaired (EOnonAD) groups across all brain regions.

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This post is Copyright: Ani Eloyan,
Maryanne Thangarajah,
Na An,
Bret J. Borowski,
Ashritha L. Reddy,
Paul Aisen,
Jeffrey L. Dage,
Tatiana Foroud,
Bernardino Ghetti,
Percy Griffin,
Dustin Hammers,
Leonardo Iaccarino,
Clifford R. Jack,
Kala Kirby,
Joel Kramer,
Robert Koeppe,
Walter A. Kukull,
Renaud La Joie,
Nidhi S Mundada,
Melissa E. Murray,
Kelly Nudelman,
Malia Rumbaugh,
David N. Soleimani‐Meigooni,
Arthur Toga,
Alexandra Touroutoglou,
Alireza Atri,
Gregory S. Day,
Ranjan Duara,
Neill R. Graff‐Radford,
Lawrence S. Honig,
David T. Jones,
Joseph Masdeu,
Mario F. Mendez,
Erik Musiek,
Chiadi U. Onyike,
Emily Rogalski,
Stephen Salloway,
Sharon Sha,
Raymond S. Turner,
Thomas S. Wingo,
David A. Wolk,
Kyle Womack,
Laurel Beckett,
Sujuan Gao,
Maria C. Carrillo,
Gil Rabinovici,
Liana G. Apostolova,
Brad Dickerson,
Prashanthi Vemuri,
and the LEADS Consortium | July 26, 2023

Wiley: Alzheimer’s & Dementia: Table of Contents