The Predict-HD study aimed to identify early signs of Huntington's disease (HD) before clinical diagnosis using genetic, neurobiological, and clinical markers. The study involved 438 participants with the HD gene mutation but no symptoms. By analyzing the relationship between estimated time to diagnosis (based on CAG repeat length and age) and clinical and neuroimaging markers, the study found that detectable changes in HD began one to two decades before diagnosis. These findings suggest that HD progression can be tracked using various markers, including motor, cognitive, and striatal volume changes. The study also highlights the importance of early detection for preventive trials and risk stratification. The results indicate that cognitive, sensory, and motor impairments begin well before diagnosis, with striatal volume loss evident up to 9–11 years prior. Functional MRI studies showed reduced activation in the basal ganglia and cingulate cortex before volumetric loss, suggesting early functional abnormalities. Animal studies support these findings, showing receptor and electrophysiological changes before behavioral symptoms. The study's longitudinal data provide a robust framework for understanding HD progression and identifying potential biomarkers for early intervention. The findings emphasize the need for further research to validate these markers and improve predictive models for HD. The study also underscores the importance of early detection and intervention in managing HD, as well as the potential for using these markers in preventive trials. The study's results contribute to the understanding of HD progression and highlight the value of early detection in improving patient outcomes.The Predict-HD study aimed to identify early signs of Huntington's disease (HD) before clinical diagnosis using genetic, neurobiological, and clinical markers. The study involved 438 participants with the HD gene mutation but no symptoms. By analyzing the relationship between estimated time to diagnosis (based on CAG repeat length and age) and clinical and neuroimaging markers, the study found that detectable changes in HD began one to two decades before diagnosis. These findings suggest that HD progression can be tracked using various markers, including motor, cognitive, and striatal volume changes. The study also highlights the importance of early detection for preventive trials and risk stratification. The results indicate that cognitive, sensory, and motor impairments begin well before diagnosis, with striatal volume loss evident up to 9–11 years prior. Functional MRI studies showed reduced activation in the basal ganglia and cingulate cortex before volumetric loss, suggesting early functional abnormalities. Animal studies support these findings, showing receptor and electrophysiological changes before behavioral symptoms. The study's longitudinal data provide a robust framework for understanding HD progression and identifying potential biomarkers for early intervention. The findings emphasize the need for further research to validate these markers and improve predictive models for HD. The study also underscores the importance of early detection and intervention in managing HD, as well as the potential for using these markers in preventive trials. The study's results contribute to the understanding of HD progression and highlight the value of early detection in improving patient outcomes.