Neuropsychol Manifestations of HD in Presymptomatics (Brandt 2002)

European Journal of Neurology, 2007

Huntington disease (HD) is a neurodegenerative disorder due to an excessive number of CAG repeats in the IT15 gene on chromosome 4. Studies of cognitive function in asymptomatic gene carriers have yielded contradictory results. This study compared cognitive performance in 44 subjects with the HD mutation (group of carriers) who had no clinical signs of HD and 39 at-risk individuals without HD mutation (group of non-carriers). Neuropsychological evaluation focused on global cognitive efficiency, psychomotor speed, attentional, executive and memory functions. Significant differences, with lower performances in the group of gene carriers, were detected for some measures of psychomotor speed, attention and executive functioning (all P < 0.01). More differences between groups were observed for memory measures, in particular on the California Verbal Memory Test. Complementing these observations, cognitive scores were correlated with age in the group of gene carriers, but not in the group of non-carriers. This suggests that the cognitive changes precede the appearance of the motor and psychiatric symptoms in HD and that tests proved to be sensitive to early HD deficiencies are better suited than global cognitive efficiency scales to observe them.

Acta Neurologica Scandinavica, 2009

Journal of Neuropsychiatry, 2008

The authors examined whether the baseline cognitive functioning of 21 clinically normal huntingtin mutation carriers who developed manifest Huntington's disease on follow-up differed from that of 49 mutation carriers who remain asymptomatic over the same period in a longitudinal study. One hundred thirty-four gene-negative offspring of Huntington's disease patients were studied as well.

This study examined whether neuropsychological changes emerge over time in asymptomatic adults who have the Huntington's disease mutation. We also evaluated whether scores on cognitive tests or psychological symptom scales varied as a function of G4G repeat length or proximity to disease onset. Twenty two healthy "mutation positive" and 37 "mutation negative" adults completed cognitive tests and psychological rating scales before disclosure of their genetic test results and on an annual basis thereafter. Repeated measures ANOVAs analysed differences between the two groups over three assessments.

Brain, 1998

The performance of 54 subjects genetically at risk for Huntington's disease was examined in double-blind fashion on a series of computerized tests from the Cambridge Neuropsychological Test Automated Battery. None of the subjects exhibited clinical movement disorder characteristic of Huntington's disease. Of the 54 subjects, 22 were Huntington's disease mutation carriers and 32 were non-carriers. On a comprehensive battery of neuropsychological tests previously shown to be sensitive to the early stages of clinical Huntington's disease, Huntington's disease mutation carriers exhibited highly specific cognitive deficits. In particular, Huntington's disease mutation carriers performed significantly less well

Journal of Clinical Neuroscience, 2009

d) Testing a demented patient; when to inform relatives. e) Affected patient in responsible position failing to inform employer. f) Permission to communicate with parents refused by at risk or mutation positive minors. g) Late life diagnosis; up to 4 generations at risk. h) Insurance denied including when mutation negative. i) Informing relatives of adopted patients of risk. j) Consequences of 2 expanded alleles/anticipation. B. Management; capacity to make appropriate decisions and give consent. a) Predictive testing; minors and intellectually disabled. b) Protecting HD patients' assets; gambling, misuse by others. c) Impulsivity including marriage,shoplifting, violent crime. d) Unsafe behaviours in insightless, demented patients. e) Driving. f) Refusing medical attention. g) Instituting enduring power of attorney and guardianship. h) Affected patient wanting IVF. i) Possible child abuse by affected parent; informing authorities. Conclusion: There are many challenges in managing HD. Situations encountered in HD management may apply to other later onset inherited disorders particularly those with behavioural changes and dementia.

Neuropsychology, 2011

Objective-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.

Cortex, 2017

Background: In Huntington's Disease (HD) cognitive decline can occur before unequivocal motor signs become apparent. As cognitive decline often starts early in the course of the disease and has a progressive nature over time, cognition can be regarded as a key target for symptomatic treatment. The specific progressive profile of cognitive decline over time is unknown. Objective: The aim of this study is to quantify the progression of cognitive decline across all HD stages, from pre-motormanifest to advanced HD, and to investigate if CAG length mediates cognitive decline. Methods: In the European REGISTRY study 2,669 HD expansion gene carriers underwent annual cognitive assessment. General linear mixed models were used to model the cognitive decline for each cognitive task across all disease stages. Additionally, a model was developed to evaluate the cognitive decline based on CAG length and age rather than disease stage. Results: There was significant cognitive decline on all administered tasks throughout pre-motormanifest (close to estimated disease onset) participants and the subsequent motormanifest participants from stage 1 to stage 4. Performance on the Stroop Word and Stroop Color tests additionally declined significantly across the two pre-motormanifest groups: far and close to estimated disease onset. The evaluation of cognition performance in relation to CAG length and age revealed a more rapid cognitive decline in participants with longer CAG length than participants with shorter CAG length over time. Cognitive decline in HD 2 Conclusion: Cognitive performance already shows decline in pre-motormanifest HD gene expansion carriers and gradually worsens to late stage HD. HD gene expansion carriers with certain CAG length have their own cognitive profile, i.e. longer CAG length is associated with more rapid decline. Highlights:  Cognitive decline is mediated by CAG length in Huntington's disease  Stroop Word and Color test are sensitive in tracking cognitive decline in HD  Cognitive decline starts early in the course of Huntington's disease

Journal of Clinical and Experimental Neuropsychology, 2009

Previous studies investigating subclinical signs of cognitive decline in presymptomatic carriers of Huntington's disease (HD) have shown conflicting results. The current study examines cognition in 105 at-risk individuals, using a broad neuropsychological test battery and adopting strict inclusion criteria for attaining a homogeneous sample. Results obtained by analyses of variance and effect size calculations indicate no clinical evidence of significant cognitive decline in asymptomatic HD carriers very far from onset of illness compared to noncarriers. Closeness to disease onset amongst gene carriers influenced cognition negatively whereas cytosine-adenineguanine (CAG) repeat size did not. The findings call for longitudinal follow-up studies using a combination of clinical instruments and experimental paradigms to pinpoint when subtle cognitive deficits occur and within which of the cognitive domains.