BackgroundHuntington'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.MethodsWe 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.ResultsIn 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.ConclusionsIGF-1 levels, unlike insulin, predict the decline of cognitive function in HD.
Huntington's disease (HD) is a rare multifactorial neurodegenerative disease. Both its natural course and any placebo effect are poorly known. All are obstacles to design randomized controlled trials (RCTs). We conducted meta-analyses of RCTs and cohorts on all parameters of the Unified Huntington's Disease Rating Scale to determine the most appropriate outcomes and to minimize the number of patients required to design RCTs in HD. Twenty-four RCTs were included, involving 838 patients with a mean age of 50.0 ± 2.3 years and a mean total functional capacity (TFC) score of 9.8 ± 0.6. Nineteen cohorts were included involving 1939 patients with a mean age of 48.9 ± 2.3 years and a mean TFC of 10.1 ± 0.7. Significant deterioration was observed in RCTs for all scores except behavioral score. Effect sizes were comparable between RCTs and cohorts for each test except that there was a significant difference for TFC. The weighted mean deterioration per year on the TFC scale was -0.5 (0.2) in RCTs and -0.8 (0.2) in cohorts. The lowest number of patients required per group in a RCT was for TFC (19 per group), whereas 30 patients would be required per group for the total motor score (TMS). For cognition, the verbal fluency test required the smallest number of patients: 104 per group. In conclusion, TMS and TFC are the most appropriate outcomes to design RCTs on HD likewise the verbal fluency test for cognition. Our results suggest an effect of placebo administration on the total functional capacity.
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