Survival in Huntington’s disease and other young‐onset dementias

Abstract

Objectives To compare survival and risk factors associated with mortality in common young‐onset dementias (YOD) including Huntington's disease. Methods This retrospective cohort study included inpatients from an Australian specialist neuropsychiatry service, over 20 years. Dementia diagnoses were based on consensus criteria and Huntington's disease (HD) was confirmed genetically. Mortality and cause of death were determined using linkage to the Australian Institute of Health and Welfare National Death Index. Results There were 386 individuals with YOD included. The dementia types included frontotemporal dementia (FTD) (24.5%), HD (21.2%) and Alzheimer's disease (AD) (20.5%). 63% (n = 243) individuals had died. The longest median survival was for those who had HD, 18.8 years from symptom onset and with a reduced mortality risk compared to AD and FTD (hazard ratio 0.5). Overall, people with YOD had significantly increased mortality, of 5–8 times, compared to the general population. Females with a YOD had higher standardised mortality ratio compared to males (9.3 vs. 4.9) overall. The most frequent cause of death in those with HD was reported as HD, with other causes of death in the other YOD‐subtypes related to dementia and mental/behavioural disorders. Discussion This is the first Australian study to investigate survival and risk factors of mortality in people with YOD. YOD has a significant risk of death compared to the general population. Our findings provide useful clinical information for people affected by YOD as well as future planning and service provision.

Brain-Derived Neurotrophic Factor Dysregulation as an Essential Pathological Feature in Huntington’s Disease: Mechanisms and Potential Therapeutics

“…There is perhaps no greater purpose associated with BDNF than its repertoire of roles at the synapse, where BDNF signaling is firmly established as a critical factor shaping synaptic development, structure, and function [ 121 ]. Loss of synaptic integrity is well-established to underpin deleterious effects on cognitive, behavioral, and motor functions [ 122 ]. Consequently, the early observations of aberrant BDNF expression in HD individuals and models quickly led to multiple lines of investigation focusing on synaptic integrity and impairments in synaptic transmission in HD.…”