From the Guidelines
Huntington disease can present as dementia, particularly in the later stages of the disease, with impairments in executive function, attention, and memory, along with personality changes and psychiatric symptoms. This neurodegenerative genetic disorder is characterized by progressive motor, cognitive, and psychiatric symptoms, affecting ~3–5 out of 100,000 individuals, with a higher prevalence in some populations of western European origin 1. The symptoms result from the selective loss of neurons, most notably in the caudate nucleus and putamen. Diagnosis requires genetic testing for the CAG trinucleotide repeat expansion in the HTT gene, with 40 or more repeats confirming the diagnosis.
There is no cure for Huntington disease, but symptomatic treatment can help manage the dementia symptoms. Medications such as tetrabenazine or deutetrabenazine may help control chorea, while antipsychotics like risperidone or olanzapine can address psychiatric symptoms. Antidepressants such as SSRIs may help with depression and irritability. Key aspects of management include:
- Cognitive rehabilitation
- Supportive care
- Genetic counseling, which is crucial for patients and families due to the autosomal dominant inheritance pattern, with each child of an affected parent having a 50% chance of inheriting the mutation. The disease typically progresses over 10-30 years, with dementia often becoming more prominent in the middle to late stages, as noted in the american college of medical genetics and genomics standards and guidelines for clinical genetics laboratories, 2014 edition: technical standards and guidelines for huntington disease 1.
From the Research
Huntington Disease Presenting as Dementia
- Huntington disease (HD) is a rare neurodegenerative disorder characterized by unwanted choreatic movements, behavioral and psychiatric disturbances, and dementia 2.
- The disease is caused by an autosomal dominant inherited mutation, specifically an elongated CAG repeat on the short arm of chromosome 4p16.3 in the Huntingtine gene 2, 3, 4.
- Cognitive decline is a common feature of HD, with patients experiencing psychiatric symptoms, cognitive impairment, and a gradual decline in psychomotor processes 2, 3.
Clinical Features and Diagnosis
- The mean age at onset of symptoms is 30-50 years, but symptoms can start before the age of 20 years, known as Juvenile Huntington's disease (JHD) 2.
- Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination 2.
- Differential diagnoses include other causes of chorea, such as general internal disorders or iatrogenic disorders, as well as phenocopies (clinically diagnosed cases of HD without the genetic mutation) 2.
Treatment and Management
- There is no cure for HD, and management is focused on treating symptoms to improve quality of life 2, 5, 6.
- Chorea is treated with dopamine receptor blocking or depleting agents, while medication and non-medical care may be required for depression and aggressive behavior 2, 5.
- Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat irritability and obsessive-compulsive behaviors associated with HD 5, 6.
- Non-pharmacological and surgical treatment strategies have not been systematically explored, but may provide additional benefits to patients with HD 5.