White matter hyperintensities are higher among early‐onset Alzheimer's disease participants than their cognitively normal and early‐onset nonAD peers: Longitudinal Early‐onset Alzheimer's Disease Study (LEADS)
Year: 2023
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: EOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD. HIGHLIGHTS: 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.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.13402
Authors: 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
Institutions: Brown University, Mayo Clinic, University of Southern California, Indiana University Indianapolis, Indiana University School of Medicine, Alzheimer's Association, University of California, San Francisco, University of Michigan, University of Washington, Mayo Clinic in Florida, Harvard University, Massachusetts General Hospital, Banner Sun Health Research Institute, Mount Sinai Medical Center, Columbia University Irving Medical Center, Houston Methodist, Weill Cornell Medicine, University of California, Los Angeles, Washington University in St. Louis, Johns Hopkins University, Johns Hopkins Medicine, Northwestern University, Stanford University, Georgetown University, Emory University, University of Pennsylvania, University of California, Davis, Indiana University – Purdue University Indianapolis
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1024368718, G1027676807, G1048051091, G1171648585, G1269895679, G1309605592, Indiana Alzheimer Disease Center, G1369195717, G1531775036, G1593128567, G1734698810, G1753564228, G1859882300, G2190936067, G2632195949, G3072607366, G3703765782, G371566797, G3727582191, G468709790, The Role of Copy Number Variants and Epigenetic Dysregulation in Early Onset Alzheimer’s Disease (EOAD), G504619356, G5056789898, LEADing Diverse Recruitment at Mayo Clinic Florida, G6246463580, G6250057130, G639043084, G6425121803, G6876577119, G7176475171, G76412088, LEADS Diversity Recruitment and Community Engagement in Rhode Island, G816726602, G8924848700, Alzheimer's Disease Research Center, Johns Hopkins Alzheimer's Disease Research Center, Arizona Alzheimer's Disease Research Center, Stanford Alzheimer's Disease Research Center, Alzheimer's Disease Research Centers, Penn Alzheimer's Disease Research Center (ADRC), National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), Massachusetts Alzheimer's Disease Research Center (MADRC), Goizueta Alzheimer's Disease Research Center
OpenAlex ID: W4385264776