Huntington's Disease Gene Expansion Carriers Are Aware of Their Degree of Apathy.

Huntington's disease is characterized by motor and behavioral symptoms as well as cognitive decline. Apathy is a common behavioral symptom, and its severity is related to disease progression. It has been suggested that Huntington's disease gene expansion carriers (HDGECs) are unaware of the signs and symptoms of the disease, which may account for their own level of awareness of their apathy. Therefore, the authors investigated the level of agreement on the degree of apathy severity between HDGECs and their proxies by using a self-report questionnaire. A total of 109 REGISTRY participants (premotormanifest, N=31; early motormanifest, N=49; and late motormanifest, N=29) and their proxies completed the Apathy Evaluation Scale. The authors used the Wilcoxon signed-rank test to assess whether gene expansion carriers and their proxies agreed on apathy severity. Scores on the Apathy Evaluation Scale significantly increased from the early motormanifest stage to the late motormanifest stage. Premotormanifest carriers scored themselves significantly higher on the Apathy Evaluation Scale than their proxies, whereas no differences were found between all motormanifest carriers and their proxies. Apathy severity increases in the motormanifest stages of Huntington's disease. HDGECs can adequately assess their level of apathy on a self-report questionnaire. These results also suggest that slight changes in the degree of apathy among premotormanifest gene expansion carriers remain unnoticed by their proxies.

Apathy and atrophy of subcortical brain structures in Huntington's disease: A two-year follow-up study.

Background: Huntington's disease (HD) is characterized by motor and behavioral symptoms, and cognitive decline. HD gene carriers and their caregivers report the behavioral and cognitive symptoms as the most burdensome. Apathy is the most common behavioral symptom of HD and is related to clinical measures of disease progression, like functional capacity. However, it is unknown whether apathy is directly related to the neurodegenerative processes in HD. Objective: The aim is to investigate whether an association between atrophy of subcortical structures and apathy is present in HD, at baseline and after 2 years follow-up. Method: Volumes of 7 subcortical structures were measured using structural T1 MRI in 171 HD gene carriers of the TRACK-HD study and apathy was assessed with the Problem Behaviors Assessment-Short, at baseline and follow-up visit. At baseline, logistic regression was used to evaluate whether volumes of subcortical brain structures were associated with the presence of apathy. Linear regression was used to assess whether subcortical atrophy was associated with the degree of apathy at baseline and with an increase in severity of apathy over time. Results: At baseline, smaller volume of the thalamus showed a higher probability of the presence of apathy in HD gene carriers, but none of the subcortical structures was associated with the degree of apathy. Over time, no association between atrophy of any subcortical structures and change in degree of apathy was found. Conclusion: The presence of apathy is associated with atrophy of the thalamus in HD, suggesting that apathy has an underlying neural cause and might explain the high incidence of apathy in HD. However, no association was found between atrophy of these subcortical structures and increase in severity of apathy over a 2-year time period.

Cognitive decline in Huntington's disease expansion gene carriers.

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 2669 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. 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.

Participants at the Leiden Site of the REGISTRY Study: A Demographic Approach.

BACKGROUND: REGISTRY is the largest European observational study of Huntington's disease (HD). The Leiden University Medical Center (LUMC) in The Netherlands is the largest recruiting site. OBJECTIVE: The aim of this paper is to give an overview of the baseline characteristics of all Leiden participants from the start of the study in 2005 until the close of REGISTRY at the LUMC in September 2014. METHODS: The Leiden cohort is described in two different ways: CAG repeat length and presence of motor signs. RESULTS: Division into groups based on prolonged CAG length revealed that the cohort consists of 4 intermediate - (27-35 CAG), 22 reduced penetrance - (36-39 CAG), 465 full penetrance - (>39 CAG) and 60 control participants (<27 CAG). The second way of dividing the participants based on present or absent of motor signs, showed that 170 pre-motormanifest - and 317 motormanifest participants were enrolled. CONCLUSION: The Leiden REGISTRY cohort at baseline is mainly characterized by full penetrance gene expansion carriers who have been clinically diagnosed with HD but who remain relatively functionally independent. For the majority of these participants, disease onset was based on motor signs followed by psychiatric and cognitive signs.