Biomarkers of Huntington's Disease Progression ID'd

Longitudinal changes in brain matter, function differ in patients with premanifest and early HD

FRIDAY, Dec. 2 (HealthDay News) -- The effect sizes of detectable Huntington's disease (HD)-related changes over 24 months can identify potential outcome measures for assessing HD progression in therapeutic trials, according to a study published online Dec. 2 in The Lancet Neurology.

Sarah J. Tabrizi, M.D., Ph.D., from the University College London, and colleagues used a prospective observational biomarker study to identify potential outcome measures for therapeutic trials. Longitudinal data were collected at baseline, 12, and 24 months from 117 individuals without HD but carrying the mutant HTT gene (premanifest HD), 116 participants with early HD, and 116 controls. The adjusted, between-group differences in the rates of change of these measures and longitudinal effect sizes were estimated.

The investigators found that, compared with controls, the premanifest and early HD groups had significantly greater progressive gray-matter, white-matter, whole-brain, and regional atrophy recorded. For participants with early HD versus controls, the effect sizes for atrophy rates were largest in the caudate (2.04) and white matter (1.70). Participants with early HD had greater deterioration of functional, quantitative motor, and cognitive measures than controls, with the symbol digit modality test showing the largest effect size. Changes in structural imaging, and cognitive and quantitative motor scores were associated with worsening total motor score (TMS) and total functional capacity, in the early HD group. In the premanifest sample, only TMS, emotion recognition, and speed tapping changed significantly over 24 months, compared with controls. Compared to other premanifest participants, the rate of brain atrophy and motor task deterioration was higher among premanifest individuals with progression.

"We document assessments from many domains showing detectable disease-related change over 24 months," the authors write.

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