Early Motor Phenotype Influences Neuropsychiatric and Cognitive Disorders in Huntington’s Disease

Congratulations Drs. Parunyou Jalayanont, Kenneth Heilman and Nikolaus McFarland on the publication of “Early Motor Phenotype Influences Neuropsychiatric and Cognitive Disorders in Huntington’s Disease,” in the April issue of Neurology.


Objective: To determine if people with early motor-manifest Huntington’s disease (HD) there are relationships between their motor phenotype and the presence of specific neuropsychiatric and neuropsychological disorders.

Background: Although classified as a movement disorder, both cognitive impairments and neuropsychiatric disturbances are major features of HD and frequently become manifest prior to the onset of motor symptoms. To date there are no studies that have explored whether HD motor phenotypes differentially influence cognitive performance and neuropsychiatric symptoms in the early stage of this disease.

Design/Methods: From the ENROLLHD study, 3,505 individuals with HD who had ≤ 5 years of motor symptoms, were classified based on the predefined Parkinsonism/chorea index into chorea-dominant (C-HD; n=1,125), Parkinsonism-dominant (P-HD; n=867) and mixed-motor phenotype (M-HD; n=1,513) groups. An analysis was performed on the results of the short Problem Behaviors Assessment. This test assesses patients for neuropsychiatric disorders such as depression, irritability/aggression, apathy, obsessive-compulsive/ perseverative behaviors, and psychosis as well as cognitive disorders by using neuropsychological tests such as the Stroop Interference test, Trail Making Test Part A and B, letter fluency, Symbol Digit Modality test and animal fluency test.

Results: In these early motor-manifest HD individuals, motor phenotype was associated with neuropsychiatric and cognitive changes. Independent of the age of motor onset, motor duration and severity of motor symptoms, the P-HD group had overall more severe neuropsychiatric disorders and poorer performance on all cognitive tests than those patients in the M-HD and C-HD groups (all p <0.001). The patients in the C-HD group had less apathy and depression than those in the M-HD group (p <0.001).

Conclusions: In the early stage of motor-manifest HD, Parkinsonism-dominant patients appear to have more severe neuropsychiatric disturbances and more cognitive impairments than those HD patients with chorea-dominant and mixed-motor phenotypes. Future studies should explore the brain mechanisms of these disorders and the possible treatments.