New Measure of Huntington’s Disease- Brain Age

Recent research in Huntington's disease (HD) has taken a significant step forward, providing new insights into the disease's progression and potential avenues for stratified treatment approaches. A collaborative effort by scientists from multiple institutions has yielded a comprehensive study that combines neuroimaging data and clinical information from 953 participants across three major HD cohorts: PREDICT-HD, TRACK-HD, and IMAGE-HD.

The primary goal of this study was to utilize brain age as a marker to better understand HD progression and identify distinct states of disease advancement. Brain age is a concept that refers to the biological age of the brain, which can be calculated using advanced neuroimaging techniques. This metric has shown potential as a means of characterizing disease progression and may facilitate the stratification of individuals for targeted clinical interventions.

The researchers began by calculating brain age for all participants and comparing it to their chronological age. Notably, they found significant differences between brain age and chronological age in HD participants compared to controls, and the disparity between the two ages increased with disease progression. This observation suggests that HD may be associated with an accelerated brain aging process.

To further investigate the states of progression in HD, the team employed a data-driven clustering method based on brain-predicted age difference (brain-PAD), which represents the difference between brain-predicted age and the participant's actual chronological age. By using brain-PAD, the researchers identified five heterogeneous states of HD progression across the disease spectrum. These distinct states allowed for a more granular understanding of the disease's varying impacts on the brain over time.

Importantly, brain-PAD was found to be associated with disease severity, as captured by the CAP (CAG and age product) score, which is a well-established measure of HD progression. Thus, brain-PAD holds promise as an additional prognostic tool to enhance the understanding of HD's trajectory.

The implications of this research are far-reaching. By providing insights into states of progression and enabling participant stratification, brain-PAD may play a crucial role in the selection of suitable individuals for future HD clinical trials. Moreover, the identification of distinct disease states can aid in the development of personalized treatment approaches for individuals at different stages of HD.

While these findings are highly promising, further research and validation will be necessary to solidify the role of brain-PAD in clinical settings. However, this study represents a crucial step forward in the quest to understand and combat Huntington's disease, offering new hope to the HD community and bringing researchers closer to the development of disease-modifying treatments.

This groundbreaking study marks a significant milestone in HD research and may pave the way for a brighter future for individuals and families affected by this challenging neurodegenerative disorder.

Journal reference:

• Preliminary scientific report. Abeyasinghe, P. et al. (2023) "Brain Age as a New Measure of Disease Stratification in Huntington's Disease". SSRN. doi: 10.2139/ssrn.4513720. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4513720