These are signs that the system in the brain that is responsible for movement has been affected. Psychomotor functions become increasingly impaired, such that any action that requires muscle control is affected. Common consequences are physical instability, abnormal facial expression, and difficulties chewing, swallowing, and speaking. Sleep disturbances and weight loss are also associated symptoms. Eating difficulties commonly cause weight loss and may lead to malnutrition. Juvenile HD generally progresses at a faster rate with greater cognitive decline, and chorea is exhibited briefly, if at all; the Westphal variant of slowness of movement, rigidity, and tremors is more typical in juvenile HD, as are seizures.Cognitive abilities are progressively impaired and tend to generally decline into dementia. Especially affected are executive functions, which include planning, cognitive flexibility, abstract thinking, rule acquisition, initiation of appropriate actions, and inhibition of inappropriate actions. As the disease progresses, memory deficits tend to appear. Reported impairments range from short-term memory deficits to long-term memory difficulties, including deficits in episodic (memory of ones life), procedural (memory of the body of how to perform an activity), and working memory.Reported neuropsychiatric signs are anxiety, depression, a reduced display of emotions, egocentrism, aggression, and compulsive behavior, the latter of which can cause or worsen addictions, including alcoholism, gambling, and hypersexuality. Difficulties in recognizing other peoples negative expressions have also been observed. The prevalence of these symptoms is highly variable between studies, with estimated rates for lifetime prevalence of psychiatric disorders between 33 and 76%.
The basal ganglia ordinarily inhibit a large number of circuits that generate specific movements. To initiate a particular movement, the cerebral cortex sends a signal to the basal ganglia that causes the inhibition to be released. Damage to the basal ganglia can cause the release or reinstatement of the inhibitions to be erratic and uncontrolled, which results in an awkward start to motion or motions to be unintentionally initiated, or a motion to be halted before, or beyond, its intended completion. The accumulating damage to this area causes the characteristic erratic movements associated with HD known as chorea, a dyskinesia. Because of the basal ganglias inability to inhibit movements, individuals affected by it inevitably experience a reduced ability to produce speech and swallow foods and liquids (dysphagia). Transcriptional dysregulation
CREB-binding protein (CBP), a transcriptional coregulator, is essential for cell function because as a coactivator at a significant number of promoters, it activates the transcription of genes for survival pathways. Furthermore, the amino acids that form CBP include a strip of 18 glutamines. Thus, the glutamines on CBP interact directly with the increased numbers of glutamine on the HTT chain and CBP gets pulled away from its typical location next to the nucleus. Specifically, CBP contains an acetyltransferase domain to which HTT binds through its polyglutamine-containing domain. Autopsied brains of those who had Huntingtons disease also have been found to have incredibly reduced amounts of CBP.