Depressive symptom severity is related to poorer cognitive performance in prodromal Huntington disease

OBJECTIVE: Depression is associated with more severe cognitive deficits in many neurological disorders, though the investigation of this relationship in Huntington disease (HD) has been limited. This study examined the relationship between depressive symptom severity and measures of executive functioning, learning/memory, and attention in prodromal HD. METHOD: Participants (814 prodromal HD, 230 gene-negative) completed a neuropsychological test battery and the Beck Depression Inventory-II (BDI-II). Based on the BDI-II, there were 637 participants with minimal depression, 89 with mild depression, 61 with moderate depression, and 27 with severe depression in the prodromal HD group. RESULTS: ANCOVA (controlling for age, sex, and education) revealed that performance on SDMT, Trails B, Hopkins Verbal Learning Test--Revised (HVLT-R) Immediate Recall, and Stroop interference was significantly different between the BDI-II severity groups, with the moderate and severe groups performing worse than the minimal and mild groups. There were no significant differences between the BDI-II severity groups for Trails A or HVLT-R Delayed Recall. Linear regression revealed that both gene status and depression severity were significant predictors of performance on all cognitive tests examined, with contributions of BDI-II and gene status comparable for Trails A, SDMT, and Stroop interference. Gene status had a higher contribution for HVLT-R Immediate and Delayed Recall and Trails B. CONCLUSIONS: Our results suggest that depressive symptom severity is related to poorer cognitive performance in individuals with prodromal HD. Though there are currently no approved therapies for cognitive impairment in HD, our findings suggest that depression may be a treatable contributor to cognitive impairment in this population

Data quality assurance and control in cognitive research: Lessons learned from the PREDICT-HD study

We discuss the strategies employed in data quality control and quality assurance for the cognitive core of Neurobiological Predictors of Huntington\u27s Disease (PREDICT-HD), a long-term observational study of over 1,000 participants with prodromal Huntington disease. In particular, we provide details regarding the training and continual evaluation of cognitive examiners, methods for error corrections, and strategies to minimize errors in the data. We present five important lessons learned to help other researchers avoid certain assumptions that could potentially lead to inaccuracies in their cognitive data

Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden.

The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (F ICV(3,877)=11.25; p<.0001; F PacedTiming(3,877)=22.89; p<.0001). When prodromal HD participants closest to HD diagnosis were compared to controls, Cohen's d effect sizes were larger in magnitude for the within-task variability measure, paced timing (-1.01), and the SDMT (-0.79) and paced tapping coefficient of variation (CV) (-0.79) compared to the measures of across-task variability [CV (0.55); intra-individual standard deviation (0.26)]. Across-task variability may be a sensitive marker of cognitive decline in individuals with prodromal HD approaching disease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample

Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden

The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (F(ICV(3,877)) = 11.25; p < .0001; F(PacedTiming(3,877)) = 22.89; p < .0001). When prodromal HD participants closest to HD diagnosis were compared to controls, Cohen’s d effect sizes were larger in magnitude for the within-task variability measure, paced timing (− 1.01), and the SDMT (− 0.79) and paced tapping coefficient of variation (CV) (− 0.79) compared to the measures of across-task variability [CV (0.55); intra-individual standard deviation (0.26)]. Across-task variability may be a sensitive marker of cognitive decline in individuals with prodromal HD approaching disease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample

Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden.

The current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (F ICV(3,877)=11.25; p&lt;.0001; F PacedTiming(3,877)=22.89; p&lt;.0001). When prodromal HD participants closest to HD diagnosis were compared to controls, Cohen's d effect sizes were larger in magnitude for the within-task variability measure, paced timing (-1.01), and the SDMT (-0.79) and paced tapping coefficient of variation (CV) (-0.79) compared to the measures of across-task variability [CV (0.55); intra-individual standard deviation (0.26)]. Across-task variability may be a sensitive marker of cognitive decline in individuals with prodromal HD approaching disease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample

The impact of oculomotor functioning on neuropsychological performance in Huntington disease

Huntington disease (HD) is a neurodegenerative condition with prominent motor (including oculomotor), cognitive, and psychiatric effects. While neuropsychological deficits are present in HD, motor impairments may impact performance on neuropsychological measures, especially those requiring a speeded response, as has been demonstrated in multiple sclerosis and schizophrenia. The current study is the first to explore associations between oculomotor functions and neuropsychological performance in HD. Participants with impaired oculomotor functioning performed worse than those with normal oculomotor functioning on cognitive tasks requiring oculomotor involvement, particularly on psychomotor speed tasks, controlling for covariates. Consideration of oculomotor dysfunction on neuropsychological performance is critical, particularly for populations with motor deficits

Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.

BackgroundNeuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD).ObjectiveDemonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures.MethodsMeasures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis ("pre-HD"). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD.ResultsCaudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures.ConclusionsResults of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology