Motor, cognitive, and functional declines contribute to a single progressive factor in early HD.

Scott A Schobel, Giuseppe Palermo, Peggy Auinger, Jeffrey D Long, Shiyang Ma, Omar S Khwaja, Dylan Trundell, Merit Cudkowicz, Steven Hersch, Cristina Sampaio, E Ray Dorsey, Blair R Leavitt, Karl D Kieburtz, Jeffrey J Sevigny, Douglas R Langbehn, Sarah J Tabrizi

Journal: Neurology 2017;89(24):2495-2502

PMID: 29142089

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Abstract

OBJECTIVE

To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials.

METHODS

We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up.

RESULTS

The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy.

CONCLUSIONS

Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures.

Address: From F. Hoffman-La Roche, Ltd (S.A.S., G.P., O.S.K., D.T., J.J.S.), Roche Innovation Center, Basel, Switzerland; University of Rochester (P.A., S.M., E.R.D., K.D.K.), NY; University of Iowa (J.D.L., D.R.L.), Iowa City; Massachusetts General Hospital and Harvard Medical School (M.C., S.H.), Boston; CHDI Management/Foundation (C.S.), Princeton, NJ; University of British Columbia, Vancouver, Canada (B.R.L.); and University College London (S.J.T.), UK. [email protected].; From F. Hoffman-La Roche, Ltd (S.A.S., G.P., O.S.K., D.T., J.J.S.), Roche Innovation Center, Basel, Switzerland; University of Rochester (P.A., S.M., E.R.D., K.D.K.), NY; University of Iowa (J.D.L., D.R.L.), Iowa City; Massachusetts General Hospital and Harvard Medical School (M.C., S.H.), Boston; CHDI Management/Foundation (C.S.), Princeton, NJ; University of British Columbia, Vancouver, Canada (B.R.L.); and University College London (S.J.T.), UK.

DOI: 10.1212/WNL.0000000000004743

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MeSH Terms: Adult, Apathy, Cognitive Dysfunction, Disease Progression, Emotions, Facial Recognition, Female, Humans, Huntington Disease, Longitudinal Studies, Male, Middle Aged, Motor Skills, Neuropsychological Tests, Prospective Studies, Randomized Controlled Trials as Topic, Reproducibility of Results, Signal-To-Noise Ratio, Social Perception, Stroop Test, Ubiquinone, Vitamins