Huntington Disease Dementia Differential Diagnoses

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

Diagnostic Considerations

The differential diagnosis of HD depends on the presenting symptoms and family history. The dementia of patients with HD, although characteristic, is not unique. Many conditions must be considered when diagnosing Huntington dementia, as follows:

Genetic disorders

Genetic disorders to consider in the differential of an adult patient who has cognitive impairment with chorea include dentatorubropallidoluysian and neuroacanthocytosis. Dentatorubropallidoluysian is rare in the United States; however, it may be considered in patients of Japanese descent. Patients with neuroacanthocytosis also may present with dementia and chorea, yet the acanthocyte hallmark pathology helps differentiate this disease.

Other genetic conditions that may be considered include Wilson disease, hereditary ataxias, benign hereditary ataxia, and mitochondrial disorders.

Gilles de la Tourette syndrome

Gilles de la Tourette syndrome is most often transmitted in an autosomal dominant pattern, but such patients have an earlier onset, show motor ticks rather than chorea, and lack the behavioral and mental changes.

Chorea

Senile chorea is a rare disorder beginning in persons older than 60 years. The abnormal movements are usually less prominent than in patients with HD, and no comparable degree of dementia develops.

A reversible adult chorea can also develop in association with lupus erythematosus or thyrotoxicosis. Reversible adult chorea has an abrupt onset and gradually disappears within weeks or months. Also, disorders that may mimic HD (eg, schizophrenia, benign familial chorea, inherited ataxias, neural acanthocytosis, familial Alzheimer disease [AD]) do not show the CAG expansion in the HD gene.

Other conditions associated with dementia

When classifying degenerative dementias, 2 major profiles may be considered. The subcortical type primarily affects attention, judgment, and behavior. This dementia pattern resembles such pathologies as HD, Parkinson disease (PD), supranuclear palsy, and dementia of the frontal lobe. Cortical dementias (eg, AD) involve the gray matter cortex and manifest with early-onset memory losses and language disturbances. Patients with subcortical dementias (eg, HD, PD, subcortical vascular dementias) have more motor symptoms than those with temporoparietal or frontal dementias. Unfortunately, clinical characteristics of cortical and subcortical dementias show a subtle overlap, which complicates a distinct diagnosis.

Patients with AD and HD can be differentiated on the basis of specific neurocognitive deficits that are independent of severity. Using the Mattis Dementia Rating Scale, at all levels of severity, patients with HD are found to be more impaired on initiation and perseveration but less impaired on memory. At moderate and severe levels of dementia, patients with HD are more impaired in constructional praxis than patients with AD. These differences relate to the cortical involvement of AD versus the subcortical involvement of HD.

As Peavy et al discussed in a study published in 2008, the criteria for diagnosing HD dementia has centered on the memory deficit characteristics of AD. [8] The authors of the study sought to propose criteria for the diagnosis of HD that focused more on functional impairment than on memory loss. The implementation of such criteria would allow for diagnosis in earlier stages, as functional deficits usually present well in advance of memory loss in the patient with HD. Peavy et al suggest that criteria for diagnosis of HD dementia include evidence of impaired speed of processing, as well as any of the following: executive function, visuospatial ability, or attention or memory deficits. Such features will follow a deteriorating course.

Patients with HD perform better than patients with AD on the immediate and delayed trials of logical memory and on the delayed trial of visual reproduction, but only at the mild stage. Patients with HD have better retention of a word list than patients with AD relative to age- and education-matched control groups. While patients with AD do poorly on the Mini-Mental State Examination, patients with HD may do as well as controls. In particular, patients with AD are impaired in learning or encoding and retention. Patients with HD show better retention and fewer tendencies toward cued intrusions. While patients with AD show deficient word storage, they tend to show particular difficulty with word retrieval in the face of relatively better word storage.

When patients with HD and patients with PD are compared, patients with HD are more impaired than patients with PD in immediate free recall and they do not exhibit the expected learning curve across trials. Patients with HD tend to exhibit a strong recency effect (ie, recalling more items from the end of the stimulus list than from the middle or beginning). Patients with PD make slightly fewer so-called errors of perseveration (ie, repetition), which is significantly fewer than the patients with HD. Patients with HD demonstrate significantly more improvement on recognition testing.

Pick disease

Pick disease affects the frontal and temporal lobes and also features more frontal or cortical signs. Clinically, it resembles HD; however, the age of onset is usually later in life and with a different underlying pathology. Early manifestations show personality and behavior changes with progressive involvement of memory and intellectual facets.

Differential Diagnoses