Delirium is associated with a host of negative outcomes, including increased risk of mortality, longer hospital stay, and poor long-term cognitive function. The pathophysiology of delirium is not well understood. Cancer patients undergoing a bone marrow transplant (BMT) are at high risk for developing delirium and Proton Magnetic Resonance Spectroscopy (1H-MRS) could lead to better understanding of the delirium process.
Fourteen BMT patients and 10 controls completed 1H-MRS, positioned above the corpus callosum, shortly after delirium onset or at study end if no delirium occurred.
In the BMT-delirium group, statistically significantly elevated tCho/tCr was found in contrast to the BMT-no delirium group (p<0.05). The BMT–delirium group also showed statistically significantly lesser NAA/tCho compared to both controls (p=0.01) and the BMT–no delirium group (p=0.04).
Elevated choline and reduced NAA indicate inflammatory processes and white matter damage as well as neuronal metabolic impairment. Further research is needed to separate the choline peaks, as well as more detailed collection of medication regimens to determine whether a higher choline concentration is a function of the delirium process or cancer treatment effects.
delirium; spectroscopy; choline; cancer; magnetic resonance imaging; cognition
Huntington disease (HD) is a neurodegenerative disease associated with cognitive, motor, and psychiatric deterioration over time. Although there is currently no cure for HD, there has been a surge of clinical trials available to patients with HD over the past 5 years. However, cognitive measures have generally been lacking from these trials. A brief, repeatable neuropsychological battery is needed to assess cognitive endpoints. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may be useful for assessing change in interventional studies or for clinical monitoring. A total of 38 patients with HD were assessed using the RBANS, other cognitive tests, and the standardized HD battery (Unified Huntington's Disease Rating Scale, UHDRS) at two clinic visits approximately 16 months apart. The RBANS Attention Index, as well as individual subtest scores on Coding, Digit Span, List Recognition, Figure Copy, and Figure Recall all declined significantly over this interval. Performance on the UHDRS cognitive tests (Symbol Digit Modalities; Stroop Color, and Stroop Word) also declined, as did functional capacity. Results suggest that cognitive changes were detected both on established cognitive tasks used in HD research and on the RBANS in patients with measurable functional decline. The RBANS provided additional information about other cognitive domains affected (e.g., memory) and may be a useful measure for tracking longitudinal change.
Huntington Disease; Neuropsychological assessment; Memory; Dementia; Executive functions
Huntington’s disease (HD) is a progressive, neuropsychiatric disorder, and limited reports indicate that risperidone might improve motor and psychiatric functioning for these patients.
In an open label, retrospective study to evaluate the effectiveness of risperidone on motor, psychiatric, and cognitive functioning in HD, 17 patients taking risperidone and 12 patients not taking any antipsychotic medication were compared across a year.
Patients taking risperidone demonstrated significantly improved psychiatric functioning and motor stabilization, whereas patients not taking risperidone were stable psychiatrically and worsened motorically.
Although controlled clinical trials are clearly needed, these preliminary results support the use of risperidone in patients with HD in treating their psychiatric and possibly motor symptoms.
Huntington’s disease; Risperidone; Treatment; Psychiatric symptoms; Motor; Cognition
Cognitive symptoms are associated with functional disability in Huntington disease; yet, few controlled trials have examined cognitive treatments that could improve patient independence and quality of life. Atomoxetine is a norepinephrine reuptake inhibitor approved for treatment of attention-deficit/hyperactivity disorder.
Twenty participants with mild Huntington disease who complained of inattention were randomized to receive atomoxetine (80 mg/d) or placebo in a 10-week double-blind crossover study. Primary outcome measures were self-reported attention and attention and executive neuropsychological composite scores. Secondary outcomes were psychiatric and motor symptom scores.
The rate of reported adverse effects while on atomoxetine was 56% (vs 35% on placebo), which most commonly included dry mouth (39%), loss of appetite (22%), insomnia (22%), and dizziness (17%). There were no serious adverse events related to atomoxetine. There were statistically significant, although mild, increases in heart rate and diastolic blood pressure on atomoxetine, consistent with other studies and not requiring medical referral. There were no significant improvements while on atomoxetine compared with placebo on primary outcomes. However, there was evidence of significant placebo effects on self-reported attention and psychiatric functions. There were no group differences on the Unified Huntington's Disease Rating total motor score.
Atomoxetine demonstrated no advantages over placebo for primary or secondary outcomes. Although atomoxetine was not effective at improving attention at this dose, its safety and tolerability were similar to other studies.
Huntington disease; randomized controlled trial; neuropsychological assessment; clinical trials
Practice effects have been widely reported in healthy older adults, but these improvements due to repeat exposure to test materials have been more equivocal in individuals with mild cognitive impairment (MCI).
The current study examined short-term practice effects in MCI by repeating a brief battery of cognitive tests across one week in 59 older adults with amnestic MCI and 62 intact older adults.
Participants with amnestic MCI showed significantly greater improvements on two delayed recall measures (p < 0.01) compared to intact peers. All other practice effects were comparable between these two groups. Practice effects significantly improved scores in the MCI group so that 49% of them were reclassified as “intact” after one week, whereas the other 51% remained “stable” as MCI. Secondary analyses indicated the MCI-Intact group demonstrated larger practice effects on two memory measures than their peers (p < 0.01).
These results continue to inform us about the nature of memory deficits in MCI, and could have implications for the diagnosis and possible treatment of this amnestic condition.
mild cognitive impairment; practice effects; repeat testing
Antidepressant usage in prodromal Huntington Disease (HD) remains uncharacterized, despite its relevance in designing experiments, studying outcomes of HD, and evaluating the efficacy of therapeutic interventions. We searched baseline medication logs of 787 prodromal HD and 215 healthy comparison (HC) participants for antidepressant use. Descriptive and mixed-effects logistic regression modeling characterized usage across participants. At baseline, approximately one in five prodromal HD participants took antidepressants. Of those, the vast majority took serotonergic antidepressants (selective serotonin reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI)). Significantly more prodromal HD participants used serotonergic antidepressants than their HC counterparts. Because of the prevalence of these medications, further analyses focused on this group alone. Mixed-effects logistic regression modeling revealed significant relationships of both closer proximity to diagnosis and female sex with greater likelihood to be prescribed a serotonergic antidepressant. More prodromal HD participants took antidepressants in general and specifically the subclass of serotonergic antidepressants than their at-risk counterparts, particularly when they were closer to predicted time of conversion to manifest HD. These propensities must be considered in studies of prodromal HD participants.
Psychiatric; Antidepressant; Neuroprotection; Clinical trials; SSRI
Obsessive and compulsive symptoms (OCS) are more prevalent in patients with diagnosed Huntington’s disease (HD) than in the general population. Although psychiatric symptoms have been reported in individuals with the HD gene expansion prior to clinical diagnosis (pre-HD), little is known about OCS in this phase of disease.
The goal of this study was to assess OCS in 300 pre-HD individuals and 108 non–gene-expanded controls from the Neurobiological Predictors of Huntington’s Disease (PREDICTHD)study (enrolled between November 2002 and April 2007) using a multidimensional, self-report measure of OCS, the Schedule of Compulsions, Obsessions, and Pathologic Impulses (SCOPI). Additionally, pre-HD individuals were classified into 3 prognostic groups on the basis of age and CAG repeat length as “near-to-onset” (< 9 estimated years to onset), “mid-to-onset” (9–15 years to onset), and “far-to-onset” (> 15 years to onset). We compared the 3 pre-HD groups to the controls on SCOPI total score and 5 subscales (checking, cleanliness, compulsive rituals, hoarding, and pathologic impulses), controlling for age and gender.
All models showed a significant (p < .05) group effect except for hoarding, with an inverted-U pattern of increasing symptoms: controls < far-to-onset < mid-to-onset, with the near-to-onset group being similar to controls. Although the mid-to-onset group showed the most pathology, mean scores were below those of patients with diagnosed obsessive-compulsive disorder. SCOPI items that separated pre-HD individuals from controls were focused on perceived cognitive errors and obsessive worrying.
Subclinical OCS were present in pre-HD participants compared to controls. The OCS phenotype in pre-HD may present with obsessive worrying and checking related to cognitive errors and may be a useful target for clinical screening as it could contribute to functional status.
We examined the gold standard for Huntington disease (HD) functional assessment, the Unified Huntington's Disease Rating Scale (UHDRS), in a group of at-risk participants not yet diagnosed but who later phenoconverted to manifest HD. We also sought to determine which skill domains first weaken and the clinical correlates of declines. Using the UHDRS Total Functional Capacity (TFC) and Functional Assessment Scale (FAS), we examined participants from Huntington Study Group clinics who were not diagnosed at their baseline visit but were diagnosed at a later visit (N = 265). Occupational decline was the most common with 65.1% (TFC) and 55.6% (FAS) reporting some loss of ability to engage in their typical work. Inability to manage finances independently (TFC 49.2%, FAS 35.1%) and drive safely (FAS 33.5%) were also found. Functional decline was significantly predicted by motor, cognitive, and depressive symptoms. The UHDRS captured early functional losses in individuals with HD prior to formal diagnosis, however, fruitful areas for expanded assessment of early functional changes are performance at work, ability to manage finances, and driving. These are also important areas for clinical monitoring and treatment planning as up to 65% experienced loss in at least one area prior to diagnosis.
Neuropsychological assessment; Depression; Daily functioning; Occupation; ADLs (activities of daily living)
This study examines perceived stress and its relationship to depressive symptoms, life changes and functional capacity in a large sample of individuals who are positive for the Huntington disease (HD) gene expansion but not yet diagnosed. Participants were classified by estimated proximity to HD diagnosis (far, mid, near) and compared with a non gene-expanded comparison group. Persons in the mid group had the highest stress scores. A significant interaction between age and time since HD genetic testing was also found. Secondary analyses using data from a different data collection point and including a diagnosed group showed the highest stress scores in the diagnosed group. Possible explanations and implications are discussed.
Huntington disease; perceived stress; depression
Practice effects on cognitive tests have been shown to further characterize patients with amnestic Mild Cognitive Impairment (aMCI), and may provide predictive information about cognitive change across time. We tested the hypothesis that a loss of practice effects would portend a worse prognosis in aMCI.
Longitudinal, observational design following participants across one year.
Three groups of older adults: 1. cognitively intact (n=57), 2. aMCI with large practice effects across one week (MCI+PE, n=25), and 3. aMCI with minimal practice effects across one week (MCI−PE, n=26).
After controlling for age and baseline cognitive differences, the MCI−PE group performed significantly worse than the other groups after one year on measures of immediate memory, delayed memory, language, and overall cognition.
Although these results need to be replicated in larger samples, the loss of short-term practice effects portends a worse prognosis in patients with aMCI.
Mild Cognitive Impairment; practice effects; dementia
Although delirium is a common medical comorbidity with altered cognition as its defining feature, few publications have addressed the neuropsychological prodrome, profile, and recovery of patients tested during delirium. We characterize neuropsychological performance in 54 hemapoietic stem cell/bone marrow transplantation (BMT) patients shortly before, during, and after delirium and in BMT patients without delirium and 10 healthy adults. Patients were assessed prospectively before and after transplantation using a brief battery. BMT patients with delirium performed more poorly than comparisons and those without delirium on cross-sectional and trend analyses. Deficits were in expected areas of attention and memory, but also in psychomotor speed and learning. The patients with delirium did not return to normative “average” on any test during observation. Most tests showed a mild decline in the visit before delirium, a sharp decline with delirium onset, and variable performance in the following days. This study adds to the few investigations of neuropsychological performance surrounding delirium and provides targets for monitoring and early detection; Trails A and B, RBANS Coding, and List Recall may be useful for delirium assessment.
Bone marrow transplantation; Cognition; Cancer; Attention; Delirium
The estimation of premorbid abilities is an essential part of a neuropsychological evaluation, especially in neurodegenerative conditions. Although word pronunciation tests are one standard method for estimating the premorbid level, research suggests that these tests may not be valid in neurodegenerative diseases. Therefore, the current study sought to examine two estimates of premorbid intellect, the Wide Range Achievement Test (WRAT) Reading subtest and the Barona formula, in 93 patients with mild to moderate Huntington's disease (HD) to determine their utility and to investigate how these measures relate to signs and symptoms of disease progression. In 89% of participants, WRAT estimates were below the Barona estimates. WRAT estimates were related to worsening memory and motor functioning, whereas the Barona estimates had weaker relationships. Neither estimate was related to depression or functional capacity. Irregular word reading tests appear to decline with HD progression, whereas estimation methods based on demographic factors may be more robust but overestimate premorbid functioning.
Huntington's disease; movement disorders; basal ganglia; assessment; dementia
PREDICT-HD is a large-scale international study of people with the Huntington Disease CAG-repeat expansion who are not yet diagnosed with HD. The objective of this study was to determine at what stage in the HD prodrome cognitive differences from CAG-normal controls can be reliably detected.
For each of 738 HD CAG-expanded participants, we computed estimated years to clinical diagnosis and probability of diagnosis in five years, based on age and CAG repeat expansion number (Langbehn, Brinkman, Falush, Paulsen, & Hayden, 2004). We then stratified the sample into groups: “NEAR,” estimated to be ≤ 9 years, “MID,” between 9 and 15 years, and “FAR,” ≥ 15 years. The control sample included 168 CAG-normal participants. Nineteen cognitive tasks were used to assess attention, working memory, psychomotor functions, episodic memory, language, recognition of facial emotion, sensory-perceptual functions, and executive functions.
Compared to the controls, the NEAR group showed significantly poorer performance on nearly all, and the MID group on about half of the cognitive tests (p = 0.05, Cohen’s d Near as large as −1.17, Mid as large as −0.61). One test even revealed significantly poorer performance in the FAR group (Cohen’s d = −0.26). Individual tasks accounted for 0.2% to 9.7% of the variance in estimated proximity to diagnosis. Overall, the cognitive battery accounted for 34% of the variance; in comparison, the UHDRS Motor Score accounted for 11.7%.
Neurocognitive tests are robust clinical indicators of the disease process prior to reaching criteria for motor diagnosis of HD.
cognitive assessment; presymptomatic; neuropsychology; psychomotor; prediagnosis
Huntington’s disease is an autosomal dominant brain disease. Although conceptualized as a neurodegenerative disease of the striatum, a growing number of studies challenge this classic concept of Huntington’s disease aetiology. Intracranial volume is the tissue and fluid within the calvarium and is a representation of the maximal brain growth obtained during development. The current study reports intracranial volume obtained from an magnetic resonance imaging brain scan in a sample of subjects (n = 707) who have undergone presymptomatic gene testing. Participants who are gene-expanded but not yet manifesting the disease (prodromal Huntington’s disease) are compared with subjects who are non-gene expanded. The prodromal males had significantly smaller intracranial volume measures with a mean volume that was 4% lower compared with controls. Although the prodromal females had smaller intracranial volume measures compared with their controls, this was not significant. The current findings suggest that mutant huntingtin can cause abnormal development, which may contribute to the pathogenesis of Huntington’s disease.
brain; brain imaging; brain volumes
The Effort Index (EI) of the RBANS was developed to assist clinicians in discriminating patients who demonstrate good effort from those with poor effort. However, there are concerns that older adults might be unfairly penalized by this index, which uses uncorrected raw scores. Using five independent samples of geriatric patients with a broad range of cognitive functioning (e.g., cognitively intact, nursing home residents, probable Alzheimer’s disease), base rates of failure on the EI were calculated. In cognitively intact and mildly impaired samples, few older individuals were classified as demonstrating poor effort (e.g., 3% in cognitively intact). However, in the more severely impaired geriatric patients, over one third had EI scores that fell above suggested cut-off scores (e.g., 37% in nursing home residents, 33% in probable Alzheimer’s disease). In the cognitively intact sample, older and less educated patients were more likely to have scores suggestive of poor effort. Education effects were observed in 3 of the 4 clinical samples. Overall cognitive functioning was significantly correlated with EI scores, with poorer cognition being associated with greater suspicion of low effort. The current results suggest that age, education, and level of cognitive functioning should be taken into consideration when interpreting EI results and that significant caution is warranted when examining EI scores in elders suspected of having dementia.
symptom validity testing; RBANS; geriatric assessment
Although current reports document a high rate of obsessive and compulsive symptoms (O/Cs) in Huntington 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 1,642 individuals with a diagnosis of HD. Of those endorsing significant O/Cs (27.2%), nearly one-quarter reported obtaining treatment for OCD. 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 had greater bradykinesia 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.
Huntington disease; obsessive compulsive symptoms; comorbidity; cognition; motor signs; psychopathology
Estimates of premorbid intellect are often used in neuropsychological assessment to make inferences about cognitive decline. To optimize the method of controlling for premorbid intellect in assessments of prodromal neurodegenerative disease, we examined performance on the American National Adult Reading Test (ANART; administered during Years 1 and 3) and the two-subtest version of the Wechsler Abbreviated Scale of Intelligence (WASI; administered in Years 2 and 4) in an ongoing prospective longitudinal study of 371 participants with prodromal Huntington disease and 51 participants with normal CAG repeats. Although both measures performed similarly, the ANART demonstrated slightly lower variability in performance over a two-year period and had slightly higher test-retest reliability than the WASI.
premorbid IQ; intelligence; neuropsychological assessment; assessment; Huntington disease; prodromal neurodegenerative disease
We examined the Trail Making Test (TMT) in a sample of 767 participants with prodromal Huntington disease (prodromal HD) and 217 healthy comparisons to determine the contributions of motor, psychiatric, and cognitive changes to TMT scores. Eight traditional and derived TMT scores were also evaluated for their ability to differentiate prodromal participants closer to estimated age of diagnosis from those farther away and prodromal individuals from healthy comparisons. Results indicate that motor signs only mildly affected part A, and psychiatric symptoms did not affect either part. Tests of perceptual processing, visual scanning, and attention were primarily associated with part A, and executive functioning (response inhibition, set-shifting), processing speed, and working memory were associated with part B. Additionally, TMT scores differentiated between healthy comparisons and prodromal HD individuals as far as 9–15 years before estimated diagnosis. In participants manifesting prodromal motor signs and psychiatric symptoms, the TMT primarily measures cognition and is able to discriminate between groups based on health status and estimated time to diagnosis.
Huntington disease; cognition; motor; psychiatric; neurodegenerative
The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has demonstrated adequate sensitivity in detecting cognitive impairment in a number of neuropsychiatric conditions, including Alzheimer's disease. However, its ability to detect milder cognitive deficits in the elderly has not been examined. The current study examined the clinical utility of the RBANS by comparing two groups: Patients with Mild Cognitive Impairment (MCI; n = 72) and cognitively intact peers (n = 71). Significant differences were observed on the RBANS Total score, 3 of the 5 Indexes, and 6 of the 12 subtests, with individuals with MCI performing worse than the comparison participants. Specificity was very good, but sensitivity ranged from poor to moderate. Areas under the receiver operating characteristic curves for the RBANS Immediate and Delayed Memory Indexes and the Total Scale score were adequate. Although significant differences were observed between groups and the areas under the curves were adequate, the lower sensitivity values of the RBANS suggests that caution should be used when diagnosing conditions such as MCI.
Mild Cognitive Impairment; Diagnostic accuracy; Repeatable Battery for the Assessment of Neuropsychological Status
Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after one year, two sets of SRBs were developed: 1. those predicting performance on the same test, and 2. those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, one year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same- and different-tests, as well as beginning to examine domain-based SRBs.
Predicting cognition; standardized based regression
This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC).
At baseline, participants in two groups (747 pr-HD: 188 NC) listened to tones presented at 550ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and various other demographic factors.
Pr-HD participants showed significantly less timing precision than NC. Cross-sectional comparison of pr-HD and NC participants showed a significant performance difference on two administration conditions of the task (dominant hand: p<.0001; alternating thumbs: p<.0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t=−11.14,df=920, p<.0001; alternating thumbs: t=−11.32, df=918, p<.0001), even considering demographic and experience variables. Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and that decline rate increases with estimated proximity to diagnosis in both conditions (dominant hand: t=−2.85,df=417, p=.0045; alternating thumbs: t=−3.56, df= 445, p=.0004). Effect sizes based on adjusted mean annual change ranged from −0.34 to 0.25 in the longitudinal model.
The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically-mediated improvement or maintenance of function.
Basal Ganglia; tapping; clinical trials; cognition; isochronous serial interval production
Huntington’s disease (HD) has been linked with fronto-subcortical neuropathology and behaviors consistent with this dysfunction. Little is known about these “frontal” behaviors in the earliest phase of the illness. Comparisons between participants in the Predict-HD study (745 “expansion-positive” and 163 “expansion-negative” controls) on the Frontal System Behavioral Scale looked for evidence of frontal behaviors, including apathy, disinhibition, and executive dysfunction. We were also able to compare participant and companion reporting of these frontal behaviors, as a possible indication of awareness of behaviors. Expansion-positive individuals reported significantly more of these frontal behaviors than expansion-negative peers. Self- and companion-reported frontal behaviors were related to other HD markers. Expansion-positive participants closest to HD diagnosis showed greater discrepancies with companions on ratings of frontal behaviors. Even though most are more than 10 years from HD diagnosis, mild frontal behaviors were present in this prediagnosed sample, which might make these behaviors useful as markers for HD onset. Participants/companions discrepancies, especially closest to HD diagnosis, might suggest early lack of awareness in these individuals.
Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington’s Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects.
Diffusion tensor imaging; fractional anisotropy; Huntington’s disease; preclinical; presymptomatic
The PREDICT-HD study seeks to identify clinical and biological markers of Huntington’s disease in premanifest individuals who have undergone predictive genetic testing.
We compared baseline motor data between gene-expansion carriers (cases) and non gene-expansion carriers (controls) using T-tests and Chi-Square. Cases were categorized as near, mid or far from diagnosis using a CAG-based formula. Striatal volumes were calculated using volumetric MRI measurements. Multiple linear regression associated total motor score, motor domains and individual motor items with estimated diagnosis and striatal volumes.
Elevated total motor scores at baseline were associated with higher genetic probability of disease diagnosis in the near future (partial R2 0.14, p<0.0001) and smaller striatal volumes (partial R2 0.15, p<0.0001). Nearly all motor domain scores showed greater abnormality with increasing proximity to diagnosis, although bradykinesia and chorea were most highly associated with diagnostic immediacy. Among individual motor items, worse scores on finger tapping, tandem gait, Luria, saccade initiation, and chorea show unique association with diagnosis probability.
Even in this premanifest population subtle motor abnormalities were associated with a higher probability of disease diagnosis and smaller striatal volumes. Longitudinal assessment will help inform whether motor items will be useful measures in preventive clinical trials.
Huntington’s disease; at-risk; UHDRS
Huntington's disease (HD) is associated with a variety of cognitive deficits, as well as motor and psychiatric disturbances. As clinical trials for HD evolve, briefer screening instruments will be needed to determine cognitive effects of interventions. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) may fill this gap. Seventy-five participants diagnosed with HD were evaluated with the RBANS, as well as several other scales typically used in HD. RBANS performances for these participants fell significantly below expectations for the Total Scale score, all five Indexes, and 11 of the 12 individual subtests. Cognitive scores on the RBANS were also significantly related to other markers of HD, including motor abnormalities, functional abilities, and other cognitive scores. Although additional research is needed, the current study supports the clinical applicability of the RBANS in patients with HD.