Profiling baseline performance on the Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS) cohort near the midpoint of data collection

Author:

Hammers Dustin B.1,Eloyan Ani2,Taurone Alexander2,Thangarajah Maryanne2,Beckett Laurel3,Gao Sujuan4,Kirby Kala1,Aisen Paul5,Dage Jeffrey L.1,Foroud Tatiana6,Griffin Percy7,Grinberg Lea T.89,Jack Clifford R.10,Kramer Joel9,Koeppe Robert11,Kukull Walter A.12,Mundada Nidhi S9,La Joie Renaud9,Soleimani‐Meigooni David N.9,Iaccarino Leonardo9,Murray Melissa E.13,Nudelman Kelly6,Polsinelli Angelina J.1,Rumbaugh Malia6,Toga Arthur14,Touroutoglou Alexandra15,Vemuri Prashanthi10,Atri Alireza16,Day Gregory S.17,Duara Ranjan18,Graff‐Radford Neill R.17,Honig Lawrence S.19,Jones David T.1020,Masdeu Joseph21,Mendez Mario F.22,Womack Kyle23,Musiek Erik23,Onyike Chiadi U.24,Riddle Meghan25,Rogalski Emily26,Salloway Steven25,Sha Sharon J.27,Turner Raymond Scott28,Wingo Thomas S.29,Wolk David A.30,Carrillo Maria C.7,Dickerson Bradford C.15,Rabinovici Gil D.9,Apostolova Liana G.1631,

Affiliation:

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. Alzheimer's Therapeutic Research Institute University of Southern California San Diego California USA

6. Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana USA

7. Medical & Scientific Relations Division Alzheimer's Association Chicago Illinois USA

8. Department of Pathology University of California – San Francisco San Francisco California USA

9. Department of Neurology University of California – San Francisco San Francisco California USA

10. Department of Radiology Mayo Clinic Rochester Minnesota USA

11. Department of Radiology University of Michigan Ann Arbor Michigan USA

12. Department of Epidemiology University of Washington Seattle Washington USA

13. Department of Neuroscience Mayo Clinic Jacksonville Florida USA

14. Laboratory of Neuro Imaging USC Stevens Neuroimaging and Informatics Institute Keck School of Medicine of USC Los Angeles California USA

15. Department of Neurology Massachusetts General Hospital and Harvard Medical School Boston Massachusetts USA

16. Banner Sun Health Research Institute Sun City Arizona USA

17. Department of Neurology Mayo Clinic Jacksonville Florida USA

18. Wien Center for Alzheimer's Disease and Memory Disorders Mount Sinai Medical Center Miami Florida USA

19. Taub Institute and Department of Neurology Columbia University Irving Medical Center New York New York USA

20. Department of Neurology Mayo Clinic Rochester Minnesota USA

21. Nantz National Alzheimer Center Houston Methodist and Weill Cornell Medicine Houston Texas USA

22. Department of Neurology David Geffen School of Medicine at UCLA Los Angeles California USA

23. Department of Neurology Washington University in St. Louis St. Louis Missouri USA

24. Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine Baltimore Maryland USA

25. Department of Neurology, Alpert Medical School Brown University Providence Rhode Island USA

26. Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine Northwestern University Chicago Illinois USA

27. Department of Neurology & Neurological Sciences Stanford University Palo Alto California USA

28. Department of Neurology Georgetown University Washington D.C. USA

29. Department of Neurology and Human Genetics Emory University School of Medicine Atlanta Georgia USA

30. Department of Neurology Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania USA

31. Department of Radiology and Imaging Sciences, Center for Neuroimaging Indiana University School of Medicine Indianapolis Indianapolis Indiana USA

Abstract

AbstractObjectiveThe Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early‐onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data‐collection mid‐point.MethodsData from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid‐positive EOAD [n = 212], and amyloid‐negative early‐onset non‐Alzheimer's disease [EOnonAD; n = 70]).ResultsCognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures.ConclusionsWe present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant.HIGHLIGHTS Findings represent the most comprehensive baseline characterization of sporadic early‐onset Alzheimer's disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

Funder

Alzheimer's Association

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

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