Abstract Details

Heterogeneity in cognitive presentations (primary progressive aphasia, posterior cortical atrophy) is now well recognized in dementing disorders. However, dementia presentations also include prominent neuropsychiatric symptoms that have not often been considered in cognitive subtypes.

We aimed to identify if there are shared clusters of clinical subtypes when including both cognitive and behavioral symptoms among neuropathology confirmed Alzheimers disease (AD) and Lewy body dementia (LBD) and mixed AD/LBD.

This is a retrospective cohort study conducted among 1,102 participants in the National Alzheimer Coordinating Center (NACC) database. These included autopsy-confirmed AD, n=558, LBD, n=101, and mixed AD-LBD, n=443 We explored baseline cognitive tests and behavioral symptoms in the Neuropsychiatry Index (NPI) at early dementia (Clinical Dementia Rating-Global=1) and identified robust clusters. Unsupervised hierarchical cluster analysis was conducted using the Gower distance. The Elbow method was employed to identify the optimal number of clusters. Differences in demographics and clinical symptoms among the clusters was investigated using the ANOVA or Pearson's chi-squared tests and post hoc pairwise comparisons with Bonferroni correction. Sensitivity analyses at higher dementia severity were conducted to further assess the robustness of the clusters.

Among all three neuropathology groups a three-clusters solution best fitted the data. Cluster1 had predominant cognitive changes, Cluster 2 had predominant behavioral changes, and Cluster 3 had a mixture of both behavioral and cognitive changes. Pooled analyses showed Cluster 1 consistently had a higher frequency of initial memory symptoms, older (>65 yrs) age of onset, and lower NPI. For LBD and mixed AD-LBD Cluster 1 also had a male predominance.

Subtypes of AD and LBD with prominent cognitive, behavioral or a combination of both changes could be robustly identified. These results are important in the recognition of patients with shared dementia phenotypes that warrants further analysis of the underlying biology and in targeting appropriate clinical care.