Cognition in HD
The diagnosis of manifest HD currently relies solely on the motor features but in recent years increasing evidence has shown that the cognitive features begin before the motor features and then evolve differently over time in different ways in different patients. We are looking at the information collected during the clinic to both describe the way in which cognition changes over time and understand how, and potentially why, this is different in different people.
In addition we are investigating whether some of the drugs we use to treat the movement problems of HD also change the thinking abilities of the individual. This has involved developed new thinking tests such as:
Dopamine and Cognition in Huntington’s Disease
This study focuses on the role of dopamine in Huntington’s disease. Dopamine (DA) is a neurotransmitter which has a regulatory role in motor function. In the early stages of HD, DA neuro-transmission is increased, contributing to hyper kinetic movements that can be alleviated with antidopaminergic medication. Despite DA being critical for certain aspects of cognition, it is currently unclear whether abnormalities in dopaminergic signalling also underly the cognitive features of HD. Furthermore, how the antidopaminergic medication used to treat the motor aspects of HD impacts on cognitive impairments is unknown.
To investigate this further, we are currently conducting a double-blind randomised placebo-controlled cross-over study called DOPA-HD, which examines the effects of pharmacologically altering dopamine on cognition in HD gene carriers and aged-matched controls. For this study, each participant attends our clinic on four separate visits, during which there is a random administration of either a dopamine agonist, dopamine antagonist, both a dopamine agonist and dopamine antagonist, or a placebo pill. After a short delay, participants complete a battery of computer-based tasks which are known to be mediated by dopamine. In addition to exploring the effects of acute DA manipulation on cognitive performance in HD, we are also analysing data collected as part of the Enroll-HD study, to assess the effects of the long-term use of dopamine antagonists on cognitive decline in HD.
In addition to these clinical studies, we are also using an organotypic hippocampal slice culture model of HD and a human induced neuronal model, derived from fibroblasts from HD patients, to explore the relationship between mutant htt expression, dopamine and neuronal dysfunction in HD.
Taken together, this work will provide insight into the relationship between DA and cognition in HD and may provide information about how DA altering therapies could be used to treat the cognitive impairments in HD.
If you would like to participate in one of the studies, or to have some more information about this research please contact Kate Harris on 01223 331160 or firstname.lastname@example.org
This trial is funded by ARUK.
In this study we are looking at the nature and significance of abnormal sleep in Huntington’s disease.
It is increasingly recognised that in many neurological conditions, sleep becomes altered long before symptoms show themselves. HD is no exception: both animal and human data suggest that both the timing and ‘architecture’ of sleep becomes abnormal in the premanifest phase, and that these changes evolve as the condition does. Sleep problems significantly influence quality of life in people with HD, and almost certainly exacerbate some of the cognitive and psychiatric symptoms of the condition. What is less clear is whether the sleep problems may even directly cause and/or accelerate these problems on a biological level.
To help resolve this, we are undertaking a longitudinal study of sleep, using polysomnography and actigraphy, in people with HD to see how sleep changes evolve in individuals across time, and how this relates to their symptoms. This is the first study of its kind. We will then soon be undertaking intervention studies to improve sleep and see what effect this has on symptoms and quality of life.
These studies are being undertaken in collaboration with Dr Alpar Lazar at the University of East Anglia (UEA).
Apathy in HD
Apathy is thought to be one of the most common psychiatric features of HD. Understanding this characteristic of the disease would help us get a deeper insight into disease progression, finding better therapies and helping improve the quality of life of people with HD.
Symptoms of apathy are associated with cognitive, motor, and functional decline. It is understood as a multidimensional syndrome with different dimensions of impaired self-generated, voluntary, and purposeful actions. The current diagnostic criteria for apathy suggest there are different subtypes with executive, emotional, cognitive, behavioural, and social dimensions. We are looking at the presence of different profiles of apathy in HD and how it can affect quality of life, and the patient’s relationship with those around them.