Huntington’s disease (HD) is an inherited disorder that causes the progressive breakdown of nerve cells in the brain, leading to decline in movement, thinking, and behavior. HD causes significant cognitive impairment that meets the criteria for dementia, though the nature of this impairment is distinct from more common types. The condition is a complex neurodegenerative process combining cognitive decline with motor and psychiatric symptoms.
Classifying Cognitive Decline in Huntington’s Disease
Dementia is an acquired decline in cognitive ability severe enough to interfere with daily life and independence. HD causes a progressive decline in mental abilities that fits this definition, leading to its classification as a form of dementia. However, the specific location of the primary brain damage in HD changes how the dementia is categorized.
HD is categorized as a subcortical dementia because it primarily affects structures beneath the cerebral cortex, specifically the basal ganglia and striatum. This contrasts with cortical dementias, like Alzheimer’s disease, where the outer layer of the brain (the cortex) is initially and most severely damaged.
The classification as a subcortical dementia explains the initial cognitive profile seen in HD. Symptoms often include a generalized slowing of thought processes, known as psychomotor slowing, and difficulties with complex mental tasks. While memory is affected, the initial and more pronounced deficits tend to be related to the underlying damage in the deeper brain structures.
The Nature of HD-Related Impairment
The cognitive impairment in Huntington’s disease follows a specific pattern that reflects the damage to the striatum and its connections to the frontal lobe. One of the most prominent early deficits involves impaired executive function. This term describes a set of mental skills that includes planning, organization, sequencing tasks, and shifting attention.
A hallmark of the HD cognitive profile is significant psychomotor slowing, or bradyphrenia. This refers to a measurable decrease in the speed of thinking and mental processing, which is independent of the physical slowing of movement. This generalized slowness impacts nearly all cognitive tasks, making multi-step processes or rapid decision-making difficult.
Memory loss in HD also presents differently than in other dementias. In the early stages, people with HD often retain the ability to form new memories and recall past events, suggesting that memory storage is relatively preserved. The primary memory difficulty is often with memory retrieval, meaning they struggle to access information that they know is stored in their brain. This contrasts with the initial and profound memory storage loss that is characteristic of Alzheimer’s disease.
Beyond Cognition The Motor and Behavioral Triad
While the cognitive decline is significant, Huntington’s disease is understood as a triad disorder, affecting motor, cognitive, and psychiatric function simultaneously. The presence of these other two components distinguishes HD from forms of dementia that are purely cognitive.
The most recognizable component of the triad is the progressive motor dysfunction. This often begins with chorea, which refers to involuntary, irregular, and unpredictable movements that can appear as fidgeting or dancing. As the disease advances, the hyperkinetic movements of chorea are typically replaced by voluntary movement impairments, such as rigidity, slow movement (bradykinesia), and problems with balance and coordination (ataxia).
The third component involves a wide range of psychiatric and behavioral disturbances that can appear years before the characteristic motor or cognitive symptoms. Common psychiatric manifestations include depression, anxiety, and extreme irritability. The behavioral spectrum also includes apathy, a loss of motivation and initiative, and obsessive-compulsive behaviors. In some cases, people may experience psychosis, which involves a loss of contact with reality, manifesting as hallucinations or delusions.
The Genetic Origin of Huntington’s Disease
Huntington’s disease is caused by a single, well-defined genetic mutation, making it a fully inherited condition. The mutation occurs in the HTT gene, which is located on chromosome 4. This gene provides instructions for making a protein called huntingtin, which is found throughout the body but is especially important in brain cells.
The mutation is a type of genetic abnormality known as a trinucleotide repeat expansion. Specifically, a sequence of three DNA building blocks—cytosine, adenine, and guanine (CAG)—is abnormally repeated multiple times within the HTT gene. In healthy individuals, the CAG segment is typically repeated 10 to 35 times.
An individual develops the disease when the number of CAG repeats reaches 36 or more. A higher number of repeats generally correlates with an earlier age of symptom onset and a more rapid disease progression. This genetic error leads to the production of an abnormally long, toxic form of the huntingtin protein that aggregates and damages neurons.
The inheritance pattern for HD is autosomal dominant, meaning a person only needs to inherit one copy of the mutated HTT gene from either parent to develop the disease. This gives a child of an affected parent a 50% chance of inheriting the condition. The genetic instability of the CAG repeat can lead to a phenomenon called anticipation, where the number of repeats increases in successive generations, often causing an earlier age of onset in children compared to their parents.