Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI

Dustin B Hammers; Ani Eloyan; Maryanne Thangarajah; Alexander Taurone; Laurel Beckett; Sujuan Gao; Angelina J Polsinelli; Kala Kirby; Jeffrey L Dage; Kelly Nudelman; Paul Aisen; Rema Reman; Renaud La Joie; Julien Lagarde; Alireza Atri; David Clark; Gregory S Day; Ranjan Duara; Neill R Graff-Radford; Lawrence S Honig; David T Jones; Joseph C Masdeu; Mario F Mendez; Kyle Womack; Erik Musiek; Chiadi U Onyike; Meghan Riddle; Ian Grant; Emily Rogalski; Erik C B Johnson; Steven Salloway; Sharon J Sha; Raymond Scott Turner; Thomas S Wingo; David A Wolk; Maria C Carrillo; Bradford C Dickerson; Gil D Rabinovici; Liana G Apostolova; LEADS Consortium 1 for the Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/alz.14218

Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI

Alzheimers Dement. 2024 Dec 23. doi: 10.1002/alz.14218. Online ahead of print.

Authors

Dustin B Hammers¹, Ani Eloyan², Maryanne Thangarajah², Alexander Taurone², Laurel Beckett³, Sujuan Gao⁴, Angelina J Polsinelli¹, Kala Kirby¹, Jeffrey L Dage¹, Kelly Nudelman⁵, Paul Aisen⁶, Rema Reman⁶, Renaud La Joie⁷, Julien Lagarde⁷, Alireza Atri⁸, David Clark¹, Gregory S Day⁹, Ranjan Duara¹⁰, Neill R Graff-Radford⁹, Lawrence S Honig¹¹, David T Jones¹², Joseph C Masdeu¹³, Mario F Mendez¹⁴, Kyle Womack¹⁵, Erik Musiek¹⁵, Chiadi U Onyike¹⁶, Meghan Riddle¹⁷, Ian Grant¹⁸, Emily Rogalski¹⁹, Erik C B Johnson²⁰, Steven Salloway¹⁷, Sharon J Sha²¹, Raymond Scott Turner²², Thomas S Wingo²³, David A Wolk²⁴, Maria C Carrillo²⁵, Bradford C Dickerson²⁶, Gil D Rabinovici^{7

27}, Liana G Apostolova^{1

5

28}; LEADS Consortium 1 for the Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Department of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
² Department of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
³ Department of Public Health Sciences, University of California-Davis, Davis, California, USA.
⁴ Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁵ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
⁶ Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
⁷ Department of Neurology, University of California-San Francisco, San Francisco, California, USA.
⁸ Banner Sun Health Research Institute, Sun City, Arizona, USA.
⁹ Department of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
¹⁰ Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, Florida, USA.
¹¹ Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
¹² Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
¹³ Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, Texas, USA.
¹⁴ Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
¹⁵ Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
¹⁶ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
¹⁷ Department of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
¹⁸ Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
¹⁹ Healthy Aging & Alzheimer's Research Care Center, Department of Neurology, University of Chicago, Chicago, Illinois, USA.
²⁰ Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.
²¹ Department of Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA.
²² Department of Neurology, Georgetown University, Washington D.C., USA.
²³ Department of Neurology, UC Davis Alzheimer's Disease Research Center, University of California-Davis, Davis, California, USA.
²⁴ Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
²⁵ Medical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
²⁶ Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
²⁷ Department of Radiology & Biomedical Imaging, University of California-San Francisco, San Francisco, California, USA.
²⁸ Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis, Indiana, USA.

PMID: 39711228
DOI: 10.1002/alz.14218

Abstract

Introduction: Early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) share similar amyloid etiology, but evidence from smaller-scale studies suggests that they manifest differently clinically. Current analyses sought to contrast the cognitive profiles of EOAD and LOAD.

Methods: Z-score cognitive-domain composites for 311 amyloid-positive sporadic EOAD and 314 amyloid-positive LOAD participants were calculated from baseline data from age-appropriate control cohorts. Z-score composites were compared between AD groups for each domain.

Results: After controlling for cognitive status, EOAD displayed worse visuospatial, executive functioning, and processing speed/attention skills relative to LOAD, and LOAD displayed worse language, episodic immediate memory, and episodic delayed memory.

Discussion: Sporadic EOAD possesses distinct cognitive profiles relative to LOAD. Clinicians should be alert for non-amnestic impairments in younger patients to ensure proper identification and intervention using disease-modifying treatments.

Highlights: Both early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD) participants displayed widespread cognitive impairments relative to their same-aged peers. Cognitive impairments were more severe for EOAD than for LOAD participants in visuospatial and executive domains. Memory and language impairments were more severe for LOAD than for EOAD participants Results were comparable after removing clinical phenotypes of posterior cortical atrophy (PCA), primary progressive aphasia (lv-PPA), and frontal-variant AD.

Keywords: Alzheimer's disease; amnestic; early‐onset; late‐onset; non‐amnestic.

Abstract

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