{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:52:11Z","timestamp":1787017931044,"version":"build-2736575974"},"reference-count":43,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dement Geriatr Cogn Disord"],"published-print":{"date-parts":[[2019]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; Alzheimer\u2019s 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. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; 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 (&lt;i&gt;p&lt;\/i&gt; &amp;#x3c; 0.05) correction was applied. Mixed-effect models were used to compute longitudinal change across clusters. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; 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. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; 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.<\/jats:p>","DOI":"10.1159\/000504341","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T17:00:34Z","timestamp":1578070834000},"page":"131-142","source":"Crossref","is-referenced-by-count":16,"title":["Neurodegenerative Patterns of Cognitive Clusters of Early-Onset Alzheimer\u2019s Disease Subjects: Evidence for Disease 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