Objective: The objective of the Predict-HD study is to use genetic, neurobiological and refined clinical markers to understand the early progression of Huntington’s disease (HD), prior to the point of traditional diagnosis, in persons with a known gene mutation. Here we estimate the approximate onset and initial course of various measurable aspects of HD relative to the time of eventual diagnosis.
Methods: We studied 438 participants who were positive for the HD gene mutation, but did not yet meet the diagnostic criteria for HD and had no functional decline. Predictability of baseline cognitive, motor, psychiatric and imaging measures was modelled non-linearly using estimated time until diagnosis (based on CAG repeat length and current age) as the predictor.
Results: Estimated time to diagnosis was related to most clinical and neuroimaging markers. The patterns of association suggested the commencement of detectable changes one to two decades prior to the predicted time of clinical diagnosis. The patterns were highly robust and consistent, despite the varied types of markers and diverse measurement methodologies.
Conclusions: These findings from the Predict-HD study suggest the approximate time scale of measurable disease development, and suggest candidate disease markers for use in preventive HD trials.
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Appendices A and B are published online only at http://jnnp.bmj.com/content/vol79/issue8
The Predict-HD Investigators, Coordinators and Cognitive Raters of the Huntington Study Group are listed in appendix B online.
Funding: National Institute of Neurological Disorders and Stroke grant No 40068, the National Institutes of Mental Health grant No 01579, Roy J Carver Trust Medicine Research Initiative, Howard Hughes Medical Institute, and High Q Foundation grants to Jane S Paulsen, the Huntington’s Disease Society of America, the Huntington’s Society of Canada, the Hereditary Disease Foundation, and the High Q Foundation grants to the Huntington Study Group. National Institute of Neurological Disorders and Stroke grant No 16375 to CAR. The NIH HD Roster Contract to Indiana University.
Competing interests: None.
Ethics approval: Study activities were reviewed and approved by institutional review boards at all study and data processing sites.
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