UCSF

Co-morbid depressive symptoms commonly present in age-related neurodegenerative diseases. Depressive symptoms impact patient outcomes adversely. Currently, there exists no early warning system for alerting providers of patients at high risk of developing depressive symptoms. This project is a retrospective study that uses the archival Flourodeoxyglucose Positron Emission Tomography (FDG-PET) dataset from Alzheimer’s Disease Neuroimaging Initiative (ADNI) to create an informatics-based approach that is capable of placing patients in one of three risk-groups for developing co-morbid depressive symptoms. Specifically, we propose an unsupervised technique to model different profiles of depressive symptom development from longitudinal clinical assessments up to 5 years. We assessed blood and Cerebrospinal fluid (CSF) biomarkers as well as FDG-PET scans as candidate biomarkers predictive of risk for cumulative depressive symptom development.Our data-driven analysis utilizing Dynamic Time Warping (DTW) and Dynamic BarycenterAveraging (DBA) revealed 3 major risk groups. The 1st group presented with the lowest baseline depressive symptoms, as indicated by their Geriatric Depression Scale (GDS) scores, (GDS=0.53± 0.67) and stayed stable over the course of ADNI study. The 2nd group presented with slightly elevated depressive symptoms at baseline (GDS=2.04 ± 1.18). Finally, the 3rd group presented with significant depressive symptoms (GDS=3.42 ± 1.40) at baseline. Groups did not differ in prevalence of females or in years of education. Patients that have Cognitive Impairments (CI),indicated by both the clinical diagnosis and the patient’s Clinical Dementia Rating (CDR), are more likely to have higher GDS scores and are at higher risk of developing depressive symptoms(i.e., baseline CI prevalence of 39.7% in Group 1 compared to 63.6% and 82.1% in Groups 2 and3, respectively). Participants in the 2nd and 3rd were more likely to progress from Mild CognitiveImpairment (MCI) to Alzheimer’s Disease (AD) (29% and 33% respectively). Participants in the3rd group had the lowest baseline Cerebrospinal fluid (CSF) tau and CSF p-tau, with respect to the1st and 2nd groups, and the highest plasma Neurofilament Light (NFL).