Rate of functional decline in Huntington's disease

K. Marder et al., Rate of functional decline in Huntington's disease, NEUROLOGY, 54(2), 2000, pp. 452-458
Citations number
Categorie Soggetti
Neurology,"Neurosciences & Behavoir
Journal title
ISSN journal
0028-3878 → ACNP
Year of publication
452 - 458
SICI code
Objective: To determine the rate of functional decline in a large cohort of patients with Huntington's disease (HD) followed at 43 sites by the Huntin gton Study Group (HSG). Methods: The annual rate of functional decline was measured using the Total Functional Capacity Scale (TFC) and the Independen ce Scale (IS) in 960 patients with definite HD followed prospectively for a mean of 18.3 months. All patients were rated with the Unified Huntington's Disease Rating Scale (UHDRS), Sample size calculations for hypothetical cl inical trials were calculated. Results: A factor analysis of the UHDRS at b aseline yielded 15 factors accounting for 77% of the variance. The TFC scor e declined at a rate of 0.72 units/year (standard error [SE] 0.04) and the IS score declined at a rate of 4.52 units/year (SE 0.23). Lower TFC score a t baseline, indicating more severe impairment, was associated with less rap id annual decline in TFC score, perhaps reflecting the floor effect of the scale. The annual rate of decline for 575 patients with baseline TFC scores of 7 to 13 was 0.97 (SE 0.06), was 0.38 (SE 0.08) for 270 patients with ba seline TFC scores of 3 to 6, and was 0.06 (SE 0.1) for 101 patients with TF C scores of 0 to 2. In multivariate analysis (n = 960), longer disease dura tion and better cognitive status at baseline were associated with a less ra pid rate of decline in TFC score, whereas depressive symptomatology was the only factor associated with more rapid decline on the IS score. Age at ons et of HD, sex, weight, and education did not affect decline on either score . Conclusions: The comparable rates of decline on the TFC and the IS scores with other published studies suggest that these estimates of functional de cline are representative of HD patients who are evaluated at HSG research s ites. In longitudinal analysis, longer disease duration and better neuropsy chological performance at baseline were associated with a less rapid rate o f decline in TFC score, whereas depressive symptomatology at baseline was a ssociated with a more rapid decline in the IS score. These rates of functio nal decline and the covariates that modify them should be considered in est imating statistical power and designing future therapeutic trials involving HD patients with early or moderately severe disease.