Psychiatric, cognitive symptoms common among Huntington’s disease gene carriers
Carriers of the Huntington’s disease gene frequently experienced “functionally debilitating” psychiatric and cognitive symptoms, according to results from a registry of more than 6,300 patients published in Neurology.
“Prospective studies of [Huntington’s disease] gene carriers many years from predicted clinical onset have shown only subtle motor, cognitive and psychiatric deficits when compared with age and sex-matched controls,” Branduff McAllister, PhD, of the division of psychological medicine and clinical neurosciences at Cardiff University in the U.K., and colleagues wrote. “This implies there is a window for therapeutic intervention to preserve normal brain functions. Understanding in detail the timing and impact of different symptoms in [Huntington’s disease] gene carriers will help improve targeted therapies.”
The investigators sought to evaluate the prevalence, timing and functional effects of psychiatric, cognitive and motor aberrations among 6,316 Huntington’s disease gene carriers by analyzing retrospective clinical data included in the European REGISTRY study, which gathered data from 161 sites in 17 countries. Participants completed the Clinical Characteristics Questionnaire, through which they provided motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior and psychosis data. The researchers analyzed associations between symptoms and functional outcomes using multiple logistic regression.
Findings demonstrated that, as age at presentation increased, the likelihood for Huntington’s disease’s first manifestation to be motor increased, and the likelihood for it to be psychiatric decreased. The first manifestation did not appear linked to pathogenic cytosine-adenine-guanine (CAG) repeat length. Huntington’s disease gene carriers frequently exhibited psychiatric and cognitive symptoms, and the researchers reported an association between longer CAG repeats and earlier onsets. A total of 42.4% of patients with Huntington’s disease reported one or more psychiatric or cognitive symptoms before motor symptoms, most commonly depression. McAllister and colleagues observed a significant decrease in total functional capacity scores linked to each non-motor symptom.
“The presence of psychiatric and cognitive symptoms in [Huntington’s disease] gene carriers is associated with significantly reduced functional capacity, emphasizing the importance of early recognition and management of these symptoms,” the researchers wrote. “Although recent models of [Huntington’s disease] staging and progression do not directly include psychiatric and cognitive symptoms, work is underway to include them in ongoing observational studies and clinical trials to improve the accuracy of clinical outcome measures.”