Phillips, Meredith L.Stage, Eddie C., Jr.Lane, Kathleen A.Gao, SujuanRisacher, Shannon L.Goukasian, NairaSaykin, Andrew J.Carrillo, Maria C.Dickerson, Bradford C.Rabinovici, Gil D.Apostolova, Liana G.2022-05-052022-05-052019Phillips ML, Stage EC Jr, Lane KA, et al. Neurodegenerative Patterns of Cognitive Clusters of Early-Onset Alzheimer's Disease Subjects: Evidence for Disease Heterogeneity. Dement Geriatr Cogn Disord. 2019;48(3-4):131-142. doi:10.1159/000504341https://hdl.handle.net/1805/28848Background/aims: 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. Methods: 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 (p < 0.05) correction was applied. Mixed-effect models were used to compute longitudinal change across clusters. Results: 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. Conclusion: 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.en-USPublisher PolicyEarly onset Alzheimer’s diseaseCognitionHeterogeneityMagnetic Resonance ImagingPositron Emission TomographyArticle