ABSTRACT
As one of the clinical triad in Huntington's disease (HD), cognitive impairment has not been widely accepted as a disease stage indicator in HD literature. This work aims to study cognitive impairment thoroughly for prodromal HD individuals with the data from a 12-year observational study to determine whether Mild Cognitive Impairment (MCI) in HD gene-mutation carriers is a defensible indicator of early disease. Prodromal HD gene-mutation carriers evaluated annually at one of 32 worldwide sites from September 2002 to April 2014 were evaluated for MCI in six cognitive domains. Linear mixed-effects models were used to determine age-, education-, and retest-adjusted cut-off values in cognitive assessment for MCI, and then the concurrent and predictive validity of MCI was assessed. Accelerated failure time (AFT) models were used to determine the timing of MCI (single-, two-, and multiple-domain), and dementia, which was defined as MCI plus functional loss. Seven hundred and sixty-eight prodromal HD participants had completed all six cognitive tasks, had MRI, and underwent longitudinal assessments. Over half (i.e., 54%) of the participants had MCI at study entry, and half of these had single-domain MCI. Compared to participants with intact cognitive performances, prodromal HD with MCI had higher genetic burden, worsened motor impairment, greater brain atrophy, and a higher likelihood of estimated HD onset. Prospective longitudinal study of those without MCI at baseline showed that 48% had MCI in subsequent visits and data visualization suggested that single-domain MCI, two-domain MCI, and dementia represent appropriate cognitive impairment staging for HD gene-mutation carriers. Findings suggest that MCI represents an early landmark of HD and may be a sensitive enrichment variable or endpoint for prodromal clinical trials of disease modifying therapeutics.
ABSTRACT
Huntington disease (HD) is a neurodegenerative condition characterized by cognitive impairments, motor abnormalities, and psychiatric disturbance. An increased risk for suicide has been documented. The majority of HD research has focused on cognitive and motor features of HD; the implications of psychiatric manifestations have received less consideration. Recent studies have sought to identify the stages of HD in which patients are at increased risk to experience suicidal ideation, though no study has examined possible risk factors for suicidality. The current study examines the presence of psychiatric comorbidity and its involvement in suicidal ideation. Suicidal ideation was examined in 1941 HD patients enrolled in the Huntington Study Group. Of those, 19% (N=369) endorsed current suicidal ideation. Logistic regression analyses indicated that depression/anxiety and aggression/irritability are significant predictors of suicidal ideation. In a subsample with the greatest suicidal ideation, alcohol and drug abuse were also predictive. It is recommended that all individuals with HD (specifically those with features of depression, aggression, substance abuse) have routine suicide assessment; further research is needed to understand the high rate of suicide in HD.
Subject(s)
Huntington Disease/epidemiology , Huntington Disease/psychology , Suicidal Ideation , Adult , Anxiety/epidemiology , Anxiety/psychology , Comorbidity , Depression/epidemiology , Depression/psychology , Disability Evaluation , Female , Humans , Logistic Models , Male , Middle Aged , Odds Ratio , Predictive Value of Tests , Severity of Illness IndexABSTRACT
Although current reports document a high rate of obsessive and compulsive symptoms (O/Cs) in Huntington's disease (HD), there have been no studies published that have made an attempt to identify comorbidities of O/Cs in HD. We examined O/Cs in 1642 individuals with a diagnosis of HD. Of those endorsing significant O/Cs (27.2%), nearly one-quarter reported obtaining treatment for obsessive compulsive disorder. Individuals with HD and O/Cs were older, had poorer functioning, and a longer duration of illness than those without O/Cs. Individuals with HD and O/Cs endorsed significantly higher psychiatric comorbidities of depression, suicidal ideation, aggression, delusions, and hallucinations. Participants with the most severe O/Cs and worse performance on the Stroop task, a measure of executive function. Clinicians should be aware that patients with HD and O/Cs might have a somewhat different clinical picture from those without, and may require a specialized treatment plan.