Trajectories of dementia-related cognitive decline in a large mental health records derived patient cohort

Background: Modeling trajectories of decline can help describe the variability in progression of cognitive impairment in dementia. Better characterisation of these trajectories has significant implications for understanding disease progression, trial design and care planning. Methods: Patients with at least three Mini-mental State Examination (MMSE) scores recorded in the South London and Maudsley NHS Foundation Trust Electronic Health Records, UK were selected (N = 3441) to form a retrospective cohort. Trajectories of cognitive decline were identified through latent class growth analysis of longitudinal MMSE scores. Demographics, Health of Nation Outcome Scales and medications were compared across trajectories identified. Results: Four of the six trajectories showed increased rate of decline with lower baseline MMSE. Two trajectories had similar initial MMSE scores but different rates of decline. In the faster declining trajectory of the two, a higher incidence of both behavioral problems and sertraline prescription were present. Conclusions: We find suggestive evidence for association of behavioral problems and sertraline prescription with rate of decline. Further work is needed to determine whether trajectories replicate in other datasets

Predicting Chronic Heart Failure Using Diagnoses Graphs

Part 5: MAKE AALInternational audiencePredicting the onset of heart disease is of obvious importance as doctors try to improve the general health of their patients. If it were possible to identify high-risk patients before their heart failure diagnosis, doctors could use that information to implement preventative measures to keep a heart failure diagnosis from becoming a reality. Integration of Electronic Medical Records (EMRs) into clinical practice has enabled the use of computational techniques for personalized healthcare at scale. The larger goal of such modeling is to pivot from reactive medicine to preventative care and early detection of adverse conditions. In this paper, we present a trajectory-based disease progression model to detect chronic heart failure. We validate our work on a database of Medicare records of 1.1 million elderly US patients. Our supervised approach allows us to assign likelihood of chronic heart failure for an unseen patient’s disease history and identify key disease progression trajectories that intensify or diminish said likelihood. This information will be a tremendous help as patients and doctors try to understand what are the most dangerous diagnoses for those who are susceptible to heart failure. Using our model, we demonstrate some of the most common disease trajectories that eventually result in the development of heart failure

Genome-wide association study of Alzheimer's disease with psychotic symptoms

International audiencePsychotic symptoms occur in approximately 40% of subjects with Alzheimer's disease (AD) and are associated with more rapid cognitive decline and increased functional deficits. They show heritability up to 61% and have been proposed as a marker for a disease subtype suitable for gene mapping efforts. We undertook a combined analysis of three genome-wide association studies (GWAS) to identify loci that a) increase susceptibility to an AD and subsequent psychotic symptoms; or b) modify risk of psychotic symptoms in the presence of neurodegeneration caused by AD. 1299 AD cases with psychosis (AD+P), 735 AD cases without psychosis (AD-P) and 5659 controls were drawn from GERAD1, the NIA-LOAD family study and the University of Pittsburgh ADRC GWAS. Unobserved genotypes were imputed to provide data on > 1.8 million SNPs. Analyses in each dataset were completed comparing a) AD+P to AD-P cases, and b) AD+P cases with controls (GERAD1, ADRC only). Aside from the APOE locus, the strongest evidence for association was observed in an intergenic region on chromosome 4 (rs753129; 'AD+PvAD-P' P=2.85 x 10-7; 'AD+PvControls' P=1.11 x 10-4). SNPs upstream of SLC2A9 (rs6834555, P=3.0x10-7) and within VSNL1 (rs4038131, P=5.9x10-7) showed strongest evidence for association with AD+P when compared to controls. These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterised