P3-384: The placebo data analysis in Alzheimer's disease and mild cognitive impairment (MCI) clinical trials project: Overview of progress in trial data collection, and key findings from the pooled MCI trial datasets

Which neuropsychiatric symptoms are most prominent varies by stage; their characterization is important for understanding disease progression and for assaying the impact of treatment. Methods: Baseline neuropsychiatric symptoms noted in 2566 subjects from three Canadian interventional studies and two SymptomGuide datasets (one clinic based, one online)were aggregated for analysis. Neuropsychiatric symptoms came from the Neuropsychiatric Inventory (NPI) or from like symptoms recorded in the SymptomGuide and included aggression, anxiety and worry, decreased interest/initiative, delusions and paranoia, hallucinations, irritability/frustration, low appetite, low mood, restlessness and sleep disturbances. Mini-Mental State Examination scores were used for staging in clinical settings. A previously validated artificial neural network method was used to stage online subjects. Symptom clusters were detected using connectivity graph analysis. In the latter, edges between each pair of nodes (representing symptoms) exist if their Fisher’s exact test for significant co-occurrence resulted in p-values less than 0.05. Open source visualization software (Gephi) was used to represent the patterns of relationships among the symptoms. Clusters were verified using principal components analysis and correspondence analysis. Results: Patients ranged from those with Mild Cognitive Impairment (MCI; n1⁄4351) to severe AD (n1⁄4522). Each of the three multivariate methods across five datasets demonstrated two clusters of neuropsychiatric symptoms. One cluster (seen in 70% people with MCI or mild dementia) was defined by significant co-occurrence of anxiety and worry, decreased interest/initiative, appetite, and lowmood. A second cluster (seen in 61% of people with moderate to severe dementia) was defined by significant co-occurrence of aggression, delusions and paranoia, hallucinations, restlessness, and irritability/frustration. Sleep disturbances were common to both clusters (13%). Conclusions: Three different analytical methods in five datasets highlighted two subgroups of neuropsychiatric symptoms. People with MCI/ mild dementia most commonly experienced symptoms of depression and mild executive dysfunction. Those in later stages of dementia experienced more severe behavioural symptoms. These symptoms groupings are consistent with the distinct affective and psychotic clusters described in prior studies.