2020 ABN Zanna Voysey

Dr Zanna Voysey

2020 ABN Fellowship

The relevance of sleep abnormalities in Huntington’s Disease to disease onset, clinical expression and progression

Sleep abnormalities are common in many forms of dementia. Recently, we have begun to understand that these not only contribute significantly to the cognitive/affective symptoms of these conditions, but may even directly accelerate the disease process. There is also growing evidence that chronic sleep deprivation, so common in modern lifestyles, may put us at risk of dementia. Sleep neurobiology is therefore a key focus of contemporary research into dementia treatment and prevention.

Huntington’s disease (HD) is a particularly useful condition to study when looking at this issue. This is because as a monogenetic, fully penetrant dementia with a prolonged prodromal phase, it facilitates the study sleep problems before and throughout the disease course, and therefore to disentangle the bidirectional relationship between sleep and symptoms/progression of dementia. Moreover, transgenic HD murine models have suggested that improving sleep can improve cognitive outcomes, but as yet there has been no translation to patients.

In this Fellowship I will undertake several unique studies. Firstly, I will complete a fourteen year study that has been tracking sleep problems, as studied by polysomnography, quantitative EEG and actigraphy, against early symptoms in individuals carrying the mutated HD gene. I will then probe causation in the associations identified through two pilot sleep therapy intervention studies. Outcome measures will include both clinical features, polysomnographic changes and fluid biomarkers of HD activity.

This work is designed to deliver the first longitudinal study of sleep in HD, the first sleep intervention studies in HD patients, and the first clinical exploration of the impact of sleep therapies on neurodegenerative pathogenesis. This bears potential to identify new, even disease-modifying treatments for HD, while also revealing novel transferrable insights into the sleep/neurodegeneration interface that cannot currently be gained from studying more common dementias.


Sleep Dysfunction in Huntington's Disease: impacts of current medications and prospects for treatment. Invited review. Journal of Huntington’s Disease

Owen NE., Barker RA., Voysey ZJ

Invited review for Journal of Huntington’s Disease 2023;12(2):149-161


Thermosensitivity of translation underlies the mammalian nocturnal-diurnal switch

Beale AD., Rzechorzek NM., Mihut A., Aiwei Z., Smyllie NJ., Pilorz V., Richardson R., Bertlesen MF., James NR., Fazal SV., Voysey Z., Pelletier J., Crosby P., Peak-Chew SY., Lancaster MA., Hut RA., O’Neill JS

BioRxiv 2023.06.22.546020, https://doi.org/10.1101/2023.06.22.546020


A 10 year study of sleep in Huntington’s disease: abnormal sleep period activity is associated with cognitive decline

Voysey Z., Goodman, AO., Rogers L., Lazar AS., Barker RA

Journal of Sleep Research 2022; 31 (S1) e13739


Circadian/diurnal rhythm profiles of serum and salivary melatonin, cortisol and cortisone, determined by liquid chromatography tandem mass spectrometry (LC-MS/MS)

Webb, B., Dunn, R., Ball, N., Fraser, W., Lazar, AS., Michalak, A., Voysey, Z., Tang, JT

Endocrine Abstracts (2022) 86: 93


The sleep and circadian problems of Huntington's disease: when, why and their importance

Voysey Z., Fazal SV, Lazar AS, Barker RA

Journal of Neurology 2021 Jun; 268(6):2275-2283


The Treatment of Sleep Dysfunction in Neurodegenerative Disorders

Voysey ZJ., Barker RA, Lazar AS

Neurotherapeutics. 2021 Jan;18(1):202-216


Actigraphic analysis of sleep and circadian disturbance in premanifest Huntington’s disease: sleep period activity increases progressively and predicts motor outcome

Lopez T., Voysey Z., Goodman, AO., Rogers L., Lazar AS., Barker RA

Journal of Sleep Research 2020; 29:s1 e13181