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1.  Managing juvenile Huntington’s disease 
Neurodegenerative disease management  2013;3(3):10.2217/nmt.13.18.
Huntington’s disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience.
PMCID: PMC3883192  PMID: 24416077
2.  Measuring Executive Dysfunction Longitudinally and in Relation to Genetic Burden, Brain Volumetrics, and Depression in Prodromal Huntington Disease 
Executive dysfunction (ED) is a characteristic of Huntington disease (HD), but its severity and progression is less understood in the prodromal phase, e.g., before gross motor abnormalities. We examined planning and problem-solving abilities using the Towers Task in HD mutation-positive individuals without motor symptoms (n = 781) and controls (n = 212). Participants with greater disease progression (determined using mutation size and current age) performed more slowly and with less accuracy on the Towers Task. Performance accuracy was negatively related to striatal volume while both accuracy and working memory were negatively related to frontal white matter volume. Disease progression at baseline was not associated with longitudinal performance over 4 years. Whereas the baseline findings indicate that ED becomes more prevalent with greater disease progression in prodromal HD and can be quantified using the Towers task, the absence of notable longitudinal findings indicates that the Towers Task exhibits limited sensitivity to cognitive decline in this population.
PMCID: PMC3569950  PMID: 23246934
Huntington's disease; Genetic disorders; Executive functions; Neuroimaging (structural); Norms/normative studies; Practice effects/reliable change; longitudinal change
3.  Perception, Experience, and Response to Genetic Discrimination in Huntington's Disease: The Australian Results of the International RESPOND-HD Study 
Aims: This study examines elements of genetic discrimination among an at-risk, clinically undiagnosed Huntington's disease (HD) population. Methods: Sixty at-risk individuals, either positive or negative for the HD genetic mutation, completed a survey regarding their experiences of genetic discrimination, adverse and unfair treatment, and knowledge about existing laws and policies surrounding genetic discrimination. Results: Sixty eight percent of participants reported feeling “Great benefit” from knowing their genetic test results. Reported benefits of knowledge included planning for the future, making decisions, and many individuals found meaning in active participation in the HD community and in advocating for themselves or families at risk for HD. Many individuals found personal meaning and a sense of community from knowledge of this information and from the ability to participate in research. Despite these positive feelings toward gene testing, results demonstrated that 33% of participants perceived experiences of genetic discrimination, which occurred repeatedly and caused great self-reported distress. Significantly, more gene-positive respondents reported experiencing incidents of genetic discrimination, compared to gene-negative respondents. At least 58 separate incidents of discrimination were reported, the number of incidents ranged from 1 to 10, with 45% of individuals (9/20 respondents) indicating more than one event. Of the most significant events of discrimination, 58% were related to insurance, 21% to employment, 16% to transactions of daily life, and 5% to relationships. Conclusion: Results contribute toward validation of empirical data regarding genetic discrimination.
PMCID: PMC3552166  PMID: 23289616
4.  Neuroanatomical correlates of cognitive functioning in prodromal Huntington disease 
Brain and Behavior  2013;4(1):29-40.
The brain mechanisms of cognitive impairment in prodromal Huntington disease (prHD) are not well understood. Although striatal atrophy correlates with some cognitive abilities, few studies of prHD have investigated whether cortical gray matter morphometry correlates in a regionally specific manner with functioning in different cognitive domains. This knowledge would inform the selection of cognitive measures for clinical trials that would be most sensitive to the target of a treatment intervention.
In this study, random forest analysis was used to identify neuroanatomical correlates of functioning in five cognitive domains including attention and information processing speed, working memory, verbal learning and memory, negative emotion recognition, and temporal processing. Participants included 325 prHD individuals with varying levels of disease progression and 119 gene-negative controls with a family history of HD. In intermediate analyses, we identified brain regions that showed significant differences between the prHD and the control groups in cortical thickness and striatal volume. Brain morphometry in these regions was then correlated with cognitive functioning in each of the domains in the prHD group using random forest methods. We hypothesized that different regional patterns of brain morphometry would be associated with performances in distinct cognitive domains.
The results showed that performances in different cognitive domains that are vulnerable to decline in prHD were correlated with regionally specific patterns of cortical and striatal morphometry. Putamen and/or caudate volumes were top-ranked correlates of performance across all cognitive domains, as was cortical thickness in regions related to the processing demands of each domain.
The results underscore the importance of identifying structural magnetic resonance imaging (sMRI) markers of functioning in different cognitive domains, as their relative sensitivity depends on the extent to which processing is called upon by different brain networks. The findings have implications for identifying neuroimaging and cognitive outcome measures for use in clinical trials.
PMCID: PMC3937704  PMID: 24653952
Cognition; magnetic resonance imaging; prodromal Huntington disease
5.  Factors associated with experiences of genetic discrimination among individuals at risk for Huntington disease 
The purpose of this study was to identify factors that are associated with experiencing genetic discrimination (GD) among individuals at risk for Huntington disease (HD). Multivariable logistic regression analysis was used to examine factors associated with experiencing GD in data from a cross-sectional, self-report survey of 293 individuals at risk for HD. The study sample comprised 167 genetically tested respondents, and 66 who were not tested (80% response rate). Overall, individuals who learn they are at risk for HD at a younger age (OR = 3.1; 95% CI: 1.5–6.2; P = 0.002), are mutation-positive (OR = 2.8; 95% CI: 1.4–6.0; P = 0.006), or are highly educated (OR = 2.7; 95% CI: 1.4–5.1; P = 0.002) are more likely to experience GD, particularly in insurance, family, and social settings. Further, younger age was associated with discrimination in insurance (OR = 0.97; 95% CI: 0.94–1.00; P = 0.038). This study provides evidence that some people who are at risk for HD were more likely to experience GD than others. Individuals who learned they are at risk for HD at a younger age and those who are mutation-positive were more likely to experience GD, particularly in insurance, family, and social settings. Younger individuals were more likely to experience discrimination in the insurance setting. Overall, highly educated individuals were also more likely to report discrimination. These results provide direction for clinical and family discussions, counseling practice, and policy aimed at mitigating experiences of GD.
PMCID: PMC3860279  PMID: 21184581
genetic discrimination; Huntington disease; genetic testing; socio-demographic factors
6.  Early Detection of Huntington Disease 
Future neurology  2010;5(1):10.2217/fnl.09.78.
Huntington disease (HD) is a devastating illness, although its autosomal dominant genetic transmission allows a unique opportunity to study apparently healthy individuals before manifest disease. Attempts to study early disease are not unique in neurology (e.g., Mild Cognitive Impairment, Vascular Cognitive Impairment), but studying otherwise-healthy appearing individuals who will go on with nearly 99% certainty to manifest the symptoms of brain disease does provide distinct but valuable information about the true natural history of the disease. The field has witnessed an explosion of research examining possible early indicators of HD during what is now referred to as the “prodrome” of HD. A NIH study in its ninth year (PREDICT-HD) has offered a glimpse into the transition from an apparently healthy state to an obviously diseased state, and can serve as a model for many other genetic diseases, both neurological and non-neurological.
PMCID: PMC3860286  PMID: 24348095
Huntington disease; diagnosis; detection; prevention; biomarkers; clinical endpoints; clinical trials
7.  MultiCenter Reliability of Diffusion Tensor Imaging 
Brain Connectivity  2012;2(6):345-355.
A number of studies are now collecting diffusion tensor imaging (DTI) data across sites. While the reliability of anatomical images has been established by a number of groups, the reliability of DTI data has not been studied as extensively. In this study, five healthy controls were recruited and imaged at eight imaging centers. Repeated measures were obtained across two imaging protocols allowing intra-subject and inter-site variability to be assessed. Regional measures within white matter were obtained for standard rotationally invariant measures: fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. Intra-subject coefficient of variation (CV) was typically <1% for all scalars and regions. Inter-site CV increased to ∼1%–3%. Inter-vendor variation was similar to inter-site variability. This variability includes differences in the actual implementation of the sequence.
PMCID: PMC3623569  PMID: 23075313
diffusion tensor; fractional anisotropy; magnetic resonance; mean diffusivity; reliability; white matter
8.  Fully Automated Analysis Using BRAINS: AutoWorkup 
NeuroImage  2010;54(1):10.1016/j.neuroimage.2010.06.047.
The BRAINS (Brain Research: Analysis of Images, Networks, and Systems) image analysis software has been in use, and in constant development, for over twenty years. The original neuroimage analysis pipeline using BRAINS was designed as a semi-automated procedure to measure volumes of the cerebral lobes and subcortical structures, requiring manual intervention at several stages in the process. Through use of advanced image processing algorithms the need for manual intervention at stages of image realignment, tissue sampling and mask editing have been eliminated. In addition, inhomogeneity correction, intensity normalization, and mask cleaning routines have been added to improve the accuracy and consistency of the results. The fully automated method, AutoWorkup, is shown in this study to be more reliable (ICC ≥ 0.96, Jaccard index ≥ 0.80 and Dice index ≥ 0.89 for all tissues in all regions) than the average of 18 manual raters. On a set of 1130 good quality scans the failure rate for correct realignment was 1.1%, and manual editing of the brain mask was required on 4% of the scans. In other tests, AutoWorkup is shown to produce measures that are reliable for data acquired across scanners, scanner vendors, and across sequences. Application of AutoWorkup for the analysis of data from the 32-site, multi-vendor PREDICT-HD study yield estimates of reliability to be greater than or equal to 0.90 for all tissues and regions.
PMCID: PMC3827877  PMID: 20600977
BRAINS; Automated image analysis; pipeline; volumetric analysis; morphometry; segmentation
9.  Cognitive domains that predict time to diagnosis in prodromal Huntington disease 
Journal of neurology, neurosurgery, and psychiatry  2012;83(6):10.1136/jnnp-2011-301732.
Prodromal Huntington disease (prHD) is associated with a myriad of cognitive changes, but the domains that best predict time to clinical diagnosis have not been studied. This is a notable gap because some domains may be more sensitive to cognitive decline, which would inform clinical trials.
The present study sought to characterize cognitive domains underlying a large test battery and for the first time, evaluate their ability to predict to time to diagnosis.
Participants included gene-negative and gene-positive prHD participants who were enrolled in the PREDICT-HD study. The CAG/Age Product (CAP) score was the measure of an individual’s genetic signature. A factor analysis of 18 tests was performed to identify sets of measures or latent factors that elucidated core constructs of tests. Factor scores were then fit to a survival model to evaluate their ability to predict time to diagnosis.
Six factors were identified: 1) speed/inhibition, 2) verbal working memory, 3) motor planning/speed, 4) attention-information integration, 5) sensory-perceptual processing, and 6) verbal learning/memory. Factor scores were sensitive to a worsening of cognitive functioning in prHD, typically more so than performances on individual tests comprising the factors. Only the motor planning/speed and sensory-perceptual processing factors predicted time to diagnosis, after controlling for CAP scores and motor symptoms.
The results suggest that motor planning/speed and sensory-perceptual processing are important markers of disease prognosis. The findings also have implications for using composite indices of cognition in preventive HD trials where they may be more sensitive than individual tests.
PMCID: PMC3812822  PMID: 22451099
prodromal Huntington Disease; time to diagnosis; cognition; survival analysis
10.  Functional imaging in Huntington’s disease 
Experimental neurology  2009;216(2):10.1016/j.expneurol.2008.12.015.
Huntington’s disease (HD) is a genetic brain disease characterized by loss of capacity in movement control, cognition, and emotional regulation over a period of about 30 years. Since it is well established that clinical impairments and brain atrophy can be detected decades prior to receiving a clinical diagnosis, functional neuroimaging efforts have gained momentum in HD research. In most brain disorders, there is accumulating evidence that the clinical manifestations of disease do not simply depend on the extent of tissue loss, but represent a complex balance among neuronal dysfunction, tissue repair, and circuitry reorganization. Based upon this premise, functional neuroimaging modalities may be more sensitive to the earliest changes in HD than are structural imaging approaches. For this review, PET and fMRI studies conducted in HD samples were summarized. Strengths and limitations of the utilization of functional imaging in HD are discussed and recommendations are offered to facilitate future research endeavors.
PMCID: PMC3810959  PMID: 19171138
Huntington’s disease; Functional imaging; PET; fMRI
11.  The emotional experiences of family carers in Huntington disease 
Journal of advanced nursing  2009;65(4):10.1111/j.1365-2648.2008.04946.x.
This paper is a report of a study conducted to examine the emotional experience of caregiving by family carers of people with Huntington disease and to describe strategies they used to deal with that experience.
Huntington disease, commonly diagnosed in young to middle adulthood, is an inherited single gene disorder involving loss of cognitive, motor and neuropsychiatric function. Many family members become caregivers as well as continuing as parents and wage earners. The emotional aspects of caregiving contribute to mental health risks for family members.
Focus groups were conducted with 42 adult carers of people with Huntington disease in four United States and two Canadian Huntington disease centers between 2001 and 2005. Data were analyzed through descriptive coding and thematic analysis.
All participants reported multiple aspects of emotional distress. Being a carer was described as experiencing disintegration of one’s life. Carers attempted to cope by seeking comfort from selected family members, anticipating the time when the care recipient had died and/or using prescription medications. Spousal carers were distressed by the loss of their relationship with their spouse and dealt with this by no longer regarding the person as an intimate partner. Carers were concerned about the disease risk for children in their families and hoped for a cure.
Emotional distress can compromise the well-being of family carers, who attempt to maintain multiple roles. Nurses should monitor carer mental health, identify sources of emotional distress and support effective strategies used by carers to mediate distress.
PMCID: PMC3807601  PMID: 19228233
caregiving; focus groups; Huntington disease; psychological impact; qualitative; research report
12.  Development of the Huntington Disease Family Concerns and Strategies Survey From Focus Group Data 
Journal of nursing measurement  2010;18(2):83-99.
Health concerns and management strategies among families of young and middle-age adults with Huntington’s disease (HD) are unknown. This study developed and tested psychometric properties of the Huntington Disease Family Concerns and Strategies Survey (HDFCSS). Focus group data from 91 adult family members were used to develop content. Content analysis yielded four domains that were transferred into Personal, Person With HD, Community Health Care Services, and Strategies scales. Focus group data, expert validation, and cognitive interviews demonstrated survey content validity. Cronbach’s alpha internal consistency coefficients for the scales were 0.83 or above. The measure can be used to generate reliable and valid data to identify adult family members’ health-related concerns and management strategies for themselves and persons with HD.
PMCID: PMC3807610  PMID: 20806651
family; Huntington’s disease; health management; focus group
13.  Huntington disease: families’ experiences of healthcare services 
Journal of advanced nursing  2010;66(3):10.1111/j.1365-2648.2009.05217.x.
This paper is a report of a study of the perceptions of family caregivers regarding the availability and adequacy of health and social care services for their family member with Huntington disease, and to compare findings from these reports in United Kingdom and United States of America samples.
Huntington disease is an inherited neurodegenerative condition. Family members often take responsibility for care of relatives with long-term conditions. Studies have demonstrated there are both positive and negative outcomes for carers.
During 2006 and 2007, respondents from the United Kingdom (n = 108) and the United States (n = 119) who were caring for a relative affected with Huntington disease completed the Community Health Care Services Scale to identify areas of concern and the extent to which specific issues bothered carers. Data were analysed using statistical tests including chi-square, t-tests and factor analysis. Results were compared between carers in the two cohorts.
Three main factors were derived: ‘community resources’, ‘individualized care’ and ‘knowledge of Huntington disease’. Carers had concerns about the knowledge of healthcare professionals providing care and thought that there were insufficient services to support them and the affected person. There were different challenges for carers when the affected person had a long-term neurodegenerative condition because these carers were also likely to have responsibilities for earning and caring for children.
Comprehensive facilities and resources are needed to support families affected by long-term complex conditions. Healthcare professionals need to be aware of the health needs of carers as well as those of the affected person.
PMCID: PMC3807640  PMID: 20423385
carers; families; healthcare services; Huntington disease; long-term condition; nursing
14.  Stability of Neuropsychological Performance in Anorexia Nervosa 
We investigated the stability of neuropsychological performance and eating disorder (EDO) symptoms before, immediately after, and 2 years after inpatient treatment. We also examined relationships between neuropsychological and EDO measures.
Sixteen women who were admitted for inpatient treatment of anorexia nervosa participated in three evaluations: (1) at admission to the hospital, (2) at discharge, and (3) at a follow-up exam approximately two years after discharge.
Body mass index increased significantly from each testing session to the next. Endorsement of eating disorder symptoms was significantly decreased at discharge and at follow-up compared to admission. In terms of cognitive performance, total scores on a brief neuropsychological battery (RBANS) were significantly greater at follow-up than at admission. We found no relationships between EDO symptoms and cognitive function at follow-up.
The current findings suggest that EDO symptoms and cognitive performance in anorexia nervosa patients can show improvement as long as two years after hospitalization, but there is no evidence that EDO symptoms are related to neuropsychological performance at that time.
PMCID: PMC3808087  PMID: 18297581
anorexia nervosa; neuropsychological functioning; body mass index
15.  Engagement with genetic discrimination: concerns and experiences in the context of Huntington disease 
It has been over 20 years since the inception of predictive testing for Huntington disease (HD), yet the social implications of knowing one's genetic risk for HD have not been fully explored. Genetic discrimination (GD) is a potential risk associated with predictive testing. Although anecdotal reports of GD have been documented, there is a paucity of research on the nature and experiences of GD in the context of HD. The purpose of this study was to describe the concerns and experiences of GD in the HD community. Semistructured interviews were conducted with 45 genetically tested and 10 untested individuals and analyzed using grounded theory methods. Our findings demonstrate that a majority of individuals were concerned about (37/55) and experienced GD (32/55) across a variety of contexts that extend beyond the traditionally examined contexts of insurance and employment to include family, social, government, and health-care domains. We describe a process of engagement with GD in which individuals formed meaningful interpretations of GD and personalized its risk and consequences in their lives. Our findings provide an insight into some of the specific processes and factors influencing engagement with GD. These results help identify areas where more education and support is needed and provide direction to genetic professionals supporting their clients as they confront issues of GD and genetic testing.
PMCID: PMC3806301  PMID: 17957229
genetic discrimination; Huntington disease; predictive testing; stigma
16.  Cognitive change in patients with Huntington disease on the Repeatable Battery for the Assessment of Neuropsychological Status 
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.
PMCID: PMC3806302  PMID: 19882420
Huntington Disease; Neuropsychological assessment; Memory; Dementia; Executive functions
17.  Development of the HD-Teen Inventory 
Clinical nursing research  2011;21(2):213-223.
Adolescents, who have a parent with Huntington Disease (HD), not only are at genetic risk for HD but also are witness to its onset and devastating clinical progression as their parent declines. To date, no mechanism has been developed to direct health care providers to the atypical adolescent experiences of these teens. The purpose of this report is to describe the process of developing the HD-Teen Inventory clinical assessment tool. Forty-eight teens and young adults from 19 U.S. states participated in the evaluation of the HD-Teen Inventory tool. Following item analysis, the number of items was reduced and item frequency and reaction scales were combined, based on the strong correlation (r = .94). The resultant tool contains 15 inventory and 2 open-ended response items. The HD-Teen Inventory emerged as a more compact and efficient tool for identifying the most salient concerns of at-risk teens in HD families in research and/or clinical practice.
PMCID: PMC3806303  PMID: 21632913
Huntington disease; adolescence; HD-Teen Inventory; field test
18.  Randomized Controlled Trial of Atomoxetine for Cognitive Dysfunction in Early Huntington Disease 
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.
PMCID: PMC3806326  PMID: 19745649
Huntington disease; randomized controlled trial; neuropsychological assessment; clinical trials
19.  Depressive Symptom Severity is Related to Poorer Cognitive Performance in Prodromal Huntington Disease 
Neuropsychology  2012;26(5):664-669.
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.
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.
ANCOVA (controlling for age, sex, and education) revealed that performance on SDMT, Trails B, 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.
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.
PMCID: PMC3806339  PMID: 22846033
Huntington disease; depression; cognitive impairment; neuropsychology
20.  Biomarkers to predict and track diseases 
Lancet neurology  2009;8(9):776-777.
PMCID: PMC3797569  PMID: 19646925
21.  Suicidal ideation in Huntington disease: The role of comorbidity 
Psychiatry research  2011;188(3):372-376.
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 1,941 HD patients enrolled in the Huntington Study Group. Of those, 19% (N = 369) reported suicidal ideation. Logistic regression analyses indicated that depression/anxiety and aggression/irritability are significant predictors of suicidal ideation (p < 0.01). In a subsample with the greatest suicidal ideation, alcohol and drug abuse were also predictive. Findings suggest that suicide in HD may be more distinct as compared to suicide in the general population. 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.
PMCID: PMC3790459  PMID: 21605914
neurodegenerative; genetic; suicide; psychiatry
22.  Short-term practice effects in amnestic mild cognitive impairment: implications for diagnosis and treatment 
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.
PMCID: PMC3789513  PMID: 18405398
mild cognitive impairment; practice effects; repeat testing
23.  Patient and Caregiver Quality of Life in Huntington’s Disease 
Little is known about subjective perceptions of quality of life (QOL) in Huntington’s disease (HD). The current study determined correlates of patient and caregiver QOL and assessed change over time. Participants were 22 patient-caregiver dyads, who rated QOL at baseline and six months later. Overall, patient functional and cognitive impairment were significantly correlated with patient and caregiver QOL. Neuropsychiatric symptoms had differential impact on patient and caregiver QOL. Furthermore, when patients recalled their QOL about a previous time, their recall may have been negatively biased. Treatment implications of results are discussed. Future work is needed because subjective QOL is an important outcome measure in therapeutic trials.
PMCID: PMC3789516  PMID: 18175350
Huntington’s disease; quality of life; caregiver; neuropsychiatric symptoms; self-report
24.  Development of the Huntington Disease Work Function Scale 
A work function measure specific for persons with prodromal Huntington disease (HD) was created to assist with workplace accommodations
A self-report HD Work Function measure (HDWF) was developed from focus group and expert validation.
Pilot studies with 238 people with prodromal HD, and 185 companions; and 89 people without prodromal HD, and 70 companions indicate HDWF has acceptable internal consistency (Cronbach’s alpha = 0.77), acceptable inter-rater reliability (r = 0.58), and acceptable convergent validity with selected items from EWPS (r = −0.56), SAS (r = −0.29), and ECog (r = −0.70). The HDWF can distinguish between people with prodromal HD and people with a HD family history who do not have prodromal HD (p < 0.0001).
The HDWF is a brief self assessment that may be used to monitor work function.
PMCID: PMC3466392  PMID: 22995807
25.  8OHdG as a marker for Huntington disease progression 
Neurobiology of disease  2012;46(3):625-634.
Leukocyte 8-hydroxydeoxyguanosine (8OHdG) is an indicator of oxidative stress, impaired metabolism, and mitochondrial dysfunction, features that have been implicated in Huntington disease (HD). Increased levels of 8OHdG have been reported in the caudate, parietal cortex, and peripherally in the serum and leukocytes, in patients diagnosed with HD. However, little is known about levels in prodromal patients and changes that might occur as the disease progresses. To address these issues, 8OHdG was tracked over time for a subset of participants enrolled in the PREDICT-HD study. Participants were stratified into four groups based on proximity to HD diagnosis at study entry: Controls (gene-negative individuals), Low (low probability of near future diagnosis), Medium, and High. Blood samples were analyzed using Liquid Chromatography Electrochemical Array, and for comparison purposes, a separate cross-sectional sample was analyzed using liquid chromatography coupled with multiple-reaction-monitoring mass spectrometry. Longitudinal data analysis showed that initial status (at study entry) and annual rate of change varied as a function of proximity group, adjusting for sex, education, age at study entry, and site effects. Overall levels were lowest for the Control group and highest for the High group, and the rate of increase varied in a similar manner. The finding that 8OHdG concentrations increased as a function of proximity to projected disease diagnosis and duration indicates support for the continued assessment of 8OHdG as a robust clinical HD biomarker.
PMCID: PMC3784019  PMID: 22414782
8OHdG; Huntington disease; Biomarker; Oxidative stress; Mitochondrial dysfunction; PREDICT-HD

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