Huntington Disease Dementia Workup

Updated: Sep 11, 2018
  • Author: Idan Sharon, MD; Chief Editor: David Bienenfeld, MD  more...
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Laboratory Studies

DNA repeat expansion

This study forms the basis of a diagnostic blood test for the HD gene. Direct gene testing via polymerase chain reaction can identify the HD gene and carrier states.

In addition to being a sensitive indicator of the inheritance of HD, CAG expansion is also highly specific because it is not observed in other neuropsychiatric disorders with which HD frequently is confused.

Dopamine homovanillic acid

In 1986, Stahl et al measured the dopamine metabolite homovanillic acid (HVA) in cerebrospinal fluid (CSF) before and after probenecid administration in healthy controls and in patients with HD. [9] Baseline CSF-HVA concentrations correlated positively with age in healthy control subjects. Baseline CSF-HVA concentrations were reduced in patients with HD, and the degree of this reduction correlated with the severity of dementia and with the duration of the disease.

In 1995, a study conducted in Spain also showed that the mean levels of HVA in the CSF of patients with HD were reduced significantly compared with those from healthy controls, patients with dystonia, individuals with other neurologic diseases, and even patients with untreated PD. [10] The clinical relevance and practicality of these findings need further research. Data suggest reduced dopamine neurotransmission in persons with HD, and this may account for the bradykinesia observed in these patients.


Imaging Studies

Computed tomography or magnetic resonance imaging

In fully developed cases, these studies show cerebral atrophy, especially of the caudate and putamen, to a degree that is almost specific to the disease.

In patients with mild-to-moderate HD, subcortical atrophy observed on an MRI is significantly correlated with specific cognitive deficits and demonstrates that cortical atrophy has an important association with the cognitive deficits in patients with HD.

Radiographically, caudate atrophy leads to the typical dilation of the frontal horns of the lateral ventricles; however, the sensitivity of a CT scan is insufficient to justify its role in the investigation of patients with suspected HD, unless genetic test findings and other diagnoses need to be excluded.

Single-photon emission computed tomography scanning

Studies using single-photon emission computed tomography scans show a decrease in glucose metabolism and cerebral blood flow in the caudate nucleus greater than that of the putamen.

Additionally, position emission tomography scanning shows decreased D1 and D2 dopamine receptor binding sites in patients with HD. This study may provide a means to track early signs of decline in individuals with the HD gene mutation prior to clinical onset.


Other Tests

Wechsler Memory Scale-Revised

Verbal and visual delayed recall on the logical memory and visual reproduction subtests of the Wechsler Memory Scale-Revised test are the 2 most sensitive neuropsychological tasks for indexing cognitive dysfunction in patients with HD.

Contrary to the poor performance of patients with AD on both recall and recognition measures, the pattern of results suggests that patients with HD have only mild-to-moderate memory impairment that results from a retrieval deficit due to frontal-striatal dysfunction.

Wisconsin Card Sorting Test

Performance on the Wisconsin Card Sorting Test has shown to be able to discriminate approximately 82% of patients with HD from healthy controls. In keeping with the clinical and neuropathological features of HD, this pattern is consistent with the widespread cognitive alterations expected from frontal-subcortical circuit dysfunction.

Trail-Making Test parts A and B versus Stroop tests

Results from tests of attention (eg, Trail-Making Test parts A and B) show moderate impairment in patients with HD. Performance on the Stroop test is more sensitive than the Trail-Making Test to attention and/or concentration deficit in patients with HD.

In summary, patients with HD are most deficient on tests of delayed recall, followed by performance on measures of memory acquisition, cognitive flexibility and abstraction, manual dexterity, attention and/or concentration, performance skills, and verbal skills.


Histologic Findings

The disease predominantly strikes the striatum. Gliosis and neuronal loss occur, especially of medium-sized spiny neurons in the caudate and putamen. Relative sparing of large, cholinergic, aspiny neurons occurs.