Huntington Disease With Parkinsonism Phenotype Linked to More Neuropsychiatric Disturbances


Findings from a large scale analysis show higher rates of cognitive impairment and neuropsychiatric disturbances in patients with parkinsonism-dominant motor-manifest individuals.

Parunyou Julayanont, MD

Parunyou Julayanont, MD

A sub-analysis of patients in the Enroll-HD database who have early motor-manifest Huntington disease (HD) demonstrated a greater correlation between those with parkinsonism-dominant phenotypes and severe neuropsychiatric disturbances and cognitive impairments than those with chorea-dominant or mixed-motor phenotypes.

“This is one of the first studies to examine the association between motor phenotypes and neuropsychiatric disturbance/cognitive performance in Huntington disease,” study author Parunyou Julayanont, MD, the Corinne Payne Wright Regent Endowed Chair in Alzheimer disease and assistant professor of neurology at Texas Tech University Health Sciences Center, told NeurologyLive. “Classifying early HD motor phenotypes may help physicians identify those individuals who may have higher risk of neuropsychiatric symptoms and cognitive deficits and focus on interventions and potential treatments.”

The study included 3505 patients with HD who had £5 years of motor symptoms and classified them into 3 subgroups: chorea-dominant (C-HD; n = 1125), parkinsonism-dominant (P-HD; n = 867), and mixed-motor (M-HD; n = 1513) phenotypes based on the predefined parkinsonism/chorea index.

Using the Problem Behaviors Assessment, investigators evaluated neuropsychiatric disturbances, including depression, apathy, irritability/aggression, obsessive-compulsive behaviors and psychosis. Assessments of executive function, processing speed, and language were completed through neuropsychological tests such as the Stroop Interference test, Trail Making Test Part A and B, word fluency, Symbol Digit Modality test and animal fluency test. Scores on the Mini-Mental State Examination served as a standard for measurement of general cognitive abilities.

Investigators found that patients with P-HD phenotypes had a greater odds of severe neuropsychiatric disturbances and significantly worse cognitive impairment (P <.001) than patients with HD who had chorea-dominant or mixed-motor phenotypes, independent of age of motor onset, motor duration and severity, CAG repeat expansion, and medication use. Overall, patients with the P-HD phenotype had significantly higher scores on 4 out of the 5 neuropsychiatric clusters, including depression (P <.001), apathy (P <.001), obsessive-compulsive behaviors (P=.003), and psychosis (P=.008). Notably, there was no significant difference observed between the groups for irritability/aggression, and apathy and depression scores were significantly lower in the C-HD group compared to the M-HD group.

Notably, patients with P-HD phenotypes had a shorter duration of motor symptoms than those in the M-HD phenotype group (P=.03). In addition, those in the P-HD group had a larger CAG expansion than the other 2 phenotype groups (P <.001).

Investigators pointed out several limitations, noting that since the study only included patients with early motor symptoms, investigators should be cautious when applying the results to a more advanced stage of the disease. In addition, 90% of the patients included in the assessment were white, which limits the generalization of the results to other nonwhite populations.

“Our study indicates that early motor HD phenotypes can be identified and may predict neuropsychiatric disturbance/cognitive performance in Huntington disease. Further studies are necessary to confirm these findings in a longitudinal fashion, but the findings do suggest that physicians should be aware of early motor phenotypes and how they might predict psychiatric and cognitive problems,” Julayanont said.


Julayanont P, Heilman KM, McFarland NR. Early-motor phenotype relates to neuropsychiatric and cognitive disorders in Huntington’s disease. Mov Disord.. Published online January 10, 2020. doi:10.1002/mds.27980.

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