Sleep disruption in Huntington's

A landmark 12-year study has revealed that specific sleep disturbances could both signal and exacerbate the progression of Huntington’s disease (HD).

Dr Zanna Voysey and colleagues from the Barker Lab at the University of Cambridge tracked 28 HD gene carriers—initially symptom-free—and 21 matched controls, using inpatient polysomnography and home-based actigraphy at baseline, 10, and 12 years. By study’s end, over half the gene carriers had developed early signs of HD.

The team identified two key sleep abnormalities: sleep stage instability, which emerged early in the pre-symptomatic phase, and sleep maintenance insomnia—frequent waking after sleep onset—which appeared closer to clinical onset. Sleep maintenance insomnia was strongly linked to poorer attention, slower thinking speed, reduced executive function, and higher levels of neurofilament light, a biomarker of neurodegeneration. These associations persisted even after accounting for disease stage, medication use, and depression.

Notably, baseline sleep stage instability predicted which participants would develop symptoms within 12 years, offering a potential biomarker for disease proximity. The findings suggest that sleep monitoring could help identify at-risk individuals before major cognitive decline and that treating insomnia might slow disease progression.

While the study’s size was limited by the rarity of HD, its longitudinal design and objective measurements make it the most comprehensive analysis of sleep in the disease to date. Intervention trials targeting sleep—possibly with emerging therapies like orexin antagonists—could benefit HD patients and provide crucial insights into sleep’s role in neurodegeneration more broadly.