Detection of Huntington's disease decades before diagnosis: the Predict-HD study

TLDR

The Predict‑HD study aims to use genetic, neurobiological, and refined clinical markers to characterize early Huntington’s disease progression before traditional diagnosis in mutation carriers. By modeling baseline cognitive, motor, psychiatric, and imaging measures non‑linearly against estimated time to diagnosis—derived from CAG repeat length and age—across 438 asymptomatic mutation carriers, the study estimates the onset and initial course of measurable HD aspects. The analysis revealed that detectable changes in clinical and neuroimaging markers begin one to two decades before predicted diagnosis, a robust pattern that identifies candidate markers for preventive trials.

Abstract

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.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.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.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.