Midpoint baseline results of the Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS)

Abstract

AbstractBackgroundFewer than 5% of patients with Alzheimer’s disease are diagnosed between 40‐64 years old, making “early‐onset Alzheimer’s disease” (EOAD) an uncommon phenomenon (Zu et al., 2015). To date, only basic knowledge on EOAD is known, no uniform criteria for EOAD have been implemented, and sample sizes in research have been small. The Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS) aims to provide a comprehensive understanding of EOAD symptomology, with the current project profiling baseline clinical, cognitive, and basic genetic characteristics of the cohort nearing the data‐collection mid‐point.MethodData from 371 participants undergoing the LEADS protocol were compared based on diagnostic group classification (cognitively normal [CN], amyloid‐positive EOAD, and amyloid‐negative Early‐Onset non‐Alzheimer’s disease [EOnonAD]). Because LEADS focuses on sporadic early‐onset dementia, impaired individuals with genetic mutations in Amyloid Precursor Protein (APP), Presenilin‐1 (PSEN1) or Presenilin‐2 (PSEN2), Microtubule Associated Protein Tau (MAPT), Chromosome 9 Open Reading Frame 72 (C9ORF72), or Granulin Precursor aka Progranulin (GRN) were excluded.ResultDemographic characteristics for each group are shown in Table 1. After adjusting for age, education, and sex, EOAD performed worse than CN for all domains (ps<.001, η2s = 0.05‐0.66), and worse than EOnonAD for all domains except language (ps<.001, η2s = 0.06‐0.29). As shown in Table 2, EOAD showed worse performance on Episodic Memory (z = ‐2.38), followed by Speed Attention (z = ‐1.93) and Executive domains (z = ‐1.43) relative to CN. An amnestic presentation was common among impaired participants, with several clinical phenotypes present. The EOAD group possessed a significantly greater proportion of apolipoprotein ε4 homozygous participants than the EOnonAD group (p = .01, Cohen’s w = 0.15), and a trend of greater proportions of ε4 heterozygous participants than both CN and EOnonAD (ps = .05‐.07, Cohen’s ws = 0.11; Table 3). Finally, LEADS participants generally consented at high rates to optional trial procedures like lumbar puncture (60%) and genetic disclosure (89%).ConclusionThis work represents the best baseline characterization of sporadic EOAD in the U.S. to date. Early‐onset dementia presents with widespread cognitive impairment, characterized by several known clinical phenotypes. Apolipoprotein ε4 allele carrier status appears to remain important in EOAD. Future investigation will explore many potential associations between EOAD and cognition, neuropsychiatric symptoms, genetics, and imaging.