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

Dustin B. Hammers, Ani Eloyan, Alexander Taurone, Maryanne Thangarajah, Laurel Beckett, Sujuan Gao, Kala Kirby, Paul Aisen, Jeffrey L. Dage, Tatiana Foroud, Percy Griffin, Lea T. Grinberg, Clifford R. Jack, Joel Kramer, Robert Koeppe, Walter A. Kukull, Nidhi S. Mundada, Renaud La Joie, David N. Soleimani-Meigooni, Leonardo IaccarinoMelissa E. Murray, Kelly Nudelman, Angelina J. Polsinelli, Malia Rumbaugh, Arthur Toga, Alexandra Touroutoglou, Prashanthi Vemuri, Alireza Atri, Gregory S. Day, Ranjan Duara, Neill R. Graff-Radford, Lawrence S. Honig, David T. Jones, Joseph Masdeu, Mario F. Mendez, Kyle Womack, Erik Musiek, Chiadi U. Onyike, Meghan Riddle, Emily Rogalski, 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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Objective: The 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. Methods: Data 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]). Results: Cognitive 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. Conclusions: We 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.

Original languageEnglish
Pages (from-to)S8-S18
JournalAlzheimer's and Dementia
Issue numberS9
StatePublished - Nov 2023


  • Alzheimer's disease
  • amnestic
  • atypical variant
  • early-onset
  • memory


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