The burden of Huntington's disease: A prospective longitudinal study of patient/caregiver pairs.

BACKGROUND: Caregiver burden is widely recognized in Huntington's disease, but little is known about the factors determining its evolution over time in the absence of longitudinal studies. Our objective was to identify typical patterns of caregiver burden level and evolution using both patients' and caregivers' characteristics over a one-year period to identify potential levers for alleviation. METHODS: We conducted a prospective multicenter longitudinal study in caregiver/patient pairs in Huntington's disease (NCT02876445) between March 2011 and May 2015. Caregiver data were derived from two questionnaires at one-year interval on perceived burden (Zarit Burden Interview), social environment and support. Caregiver data were linked to clinical and demographic data from patients included in the Biomarker study (NCT01590589). Unsupervised clustering analysis was performed using self-organizing maps. RESULTS: 105 caregiver/patient pairs were included in the analysis. We identified four clusters. Of the two clusters of patients with advanced disease, cluster A was characterized by high levels of irritability and obsessive-compulsive behaviors, with high and increasing burden (N = 30; 29%), cluster B, the more apathetic group, with low and decreasing burden (N = 22; 21%). Clusters C (N = 27; 26%) and D (N = 26; 25%) were composed of patients in earlier stages, associated with a stable burden in group C but a notably increasing one in group D driven by patients' depression scores increase. CONCLUSIONS: Our results revealed the dynamics of caregiver burden over time in Huntington's disease, combining the stage of the disease, the severity of the patients' decline, psychiatric and behavioral disorders, and their evolution over time.

Insulin-Like Growth Factor-1 but Not Insulin Predicts Cognitive Decline in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is one of several neurodegenerative disorders that have been associated with metabolic alterations. Changes in Insulin Growth Factor 1 (IGF-1) and/or insulin input to the brain may underlie or contribute to the progress of neurodegenerative processes. Here, we investigated the association over time between changes in plasma levels of IGF-1 and insulin and the cognitive decline in HD patients. METHODS: We conducted a multicentric cohort study in 156 patients with genetically documented HD aged from 22 to 80 years. Among them, 146 patients were assessed at least twice with a follow-up of 3.5 ± 1.8 years. We assessed their cognitive decline using the Unified Huntington's Disease Rating Scale, and their IGF-1 and insulin plasmatic levels, at baseline and once a year during the follow-up. Associations were evaluated using a mixed-effect linear model. RESULTS: In the cross-sectional analysis at baseline, higher levels of IGF-1 and insulin were associated with lower cognitive scores and thus with a higher degree of cognitive impairment. In the longitudinal analysis, the decrease of all cognitive scores, except the Stroop interference, was associated with the IGF-1 level over time but not of insulin. CONCLUSIONS: IGF-1 levels, unlike insulin, predict the decline of cognitive function in HD.