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Phillips, Meredith L.; Stage, Jr., Eddie C.; Lane, Kathleen A.; Gao, Sujuan; Risacher, Shannon L.; Goukasian, Naira; Saykin, Andrew J.; Carrillo, Maria C.; Dickerson, Bradford C.; Rabinovici, Gil D.; Apostolova, Liana G.

Neurodegenerative Patterns of Cognitive Clusters of Early-Onset Alzheimer’s Disease Subjects: Evidence for Disease Heterogeneity

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  • Media type: E-Article
  • Title: Neurodegenerative Patterns of Cognitive Clusters of Early-Onset Alzheimer’s Disease Subjects: Evidence for Disease Heterogeneity
  • Contributor: Phillips, Meredith L.; Stage, Jr., Eddie C.; Lane, Kathleen A.; Gao, Sujuan; Risacher, Shannon L.; Goukasian, Naira; Saykin, Andrew J.; Carrillo, Maria C.; Dickerson, Bradford C.; Rabinovici, Gil D.; Apostolova, Liana G.
  • Published: S. Karger AG, 2019
  • Published in: Dementia and Geriatric Cognitive Disorders, 48 (2019) 3-4, Seite 131-142
  • Language: English
  • DOI: 10.1159/000504341
  • ISSN: 1421-9824; 1420-8008
  • Origination:
  • Footnote:
  • Description: <b><i>Background/Aims:</i></b> Alzheimer’s disease (AD) with onset before 65 (early-onset AD [EOAD]) occurs in approximately 6% of cases and can affect nonmemory domains. Here, we analyze patterns of impairment in amnestic EOAD individuals using data-driven statistical analyses. <b><i>Methods:</i></b> Cognitive data of 146 EOAD subjects were Z-normalized to 395 cognitively normal (CN) individuals. Domain-averaged Z-scores were adjusted for age, sex, and education followed by Wald cluster analysis of residuals. Magnetic resonance imaging and positron emission tomography comparisons of EOAD clusters to age-matched CN were done using Statistic Parametric Mapping 8. Cluster-level-family-wise error (<i>p</i> < 0.05) correction was applied. Mixed-effect models were used to compute longitudinal change across clusters. <b><i>Results:</i></b> Scree plot using the pseudo-T-squared suggested a 4-cluster solution. Cluster 1 (memory-predominant impairment) showed atrophy/hypometabolism in medial/lateral temporal, lateral parietal, and posterior cingulate regions. Cluster 2 (memory/visuospatial-predominant) showed atrophy/hypometabolism of medial temporal, temporoparietal, and frontal cortices. Cluster 3 (memory, language, and executive function) and Cluster 4 (globally impaired) manifested atrophy and hypometabolism throughout the brain. Longitudinally between-cluster differences in the visuospatial and language/executive domains were significant, suggesting phenotypic variation. <b><i>Conclusion:</i></b> We observed significant heterogeneity in cognitive presentation among amnestic EOAD subjects and patterns of atrophy/hypometabolism in each cluster in agreement with the observed cognitive phenotype.