On the association between apathy and deficits of social cognition and executive functions in Huntington's disease.

OBJECTIVE: To investigate if executive and social cognitive dysfunction was associated with apathy in a large cohort of Huntington's disease gene expansion carriers. METHOD: Eighty premanifest and motor-manifest Huntington's disease gene expansion carriers (Mini-Mental State Examination score ≥ 24 and Montreal Cognitive Assessment score ≥ 19) and thirty-two controls were examined with the Lille Apathy Rating Scale (LARS), a tailored and quantitative measure of apathy, and a comprehensive cognitive battery on executive functions and social cognition (emotion recognition, theory of mind and sarcasm detection), as well as general correlates like demographic variables, and neuropsychiatric and cognitive screening tests. RESULTS: The motor-manifest Huntington's disease gene expansion carriers had significantly different scores on most measures of social cognition and executive functions, compared to premanifest and control participants. Apathy was significantly correlated with most executive test scores, but the Emotion Hexagon was the only social cognitive test score significantly correlated with apathy. We found that the motor score and the depression score were the only significant predictors of the apathy score, when the social cognitive and executive tests with the strongest association with the global LARS score were entered into a multiple stepwise regression model. No cognitive test score could significantly predict apathy. The model explained 21 % of the total variance. CONCLUSION: Despite being significantly correlated with apathy neuropsychological variables did not have a significant impact on apathy when variables as depression and motor symptoms were taken into account. Apathy should be considered an independent symptom of Huntington's disease that requires specific examination.

An Exploratory Study Investigating Autonomy in Huntington's Disease Gene Expansion Carriers.

BACKGROUND: Autonomy describes a psychological state of self-regulation of motivation and action, which is a central characteristic of healthy functioning. In neurodegenerative diseases measures of self-perception have been found to be affected by the disease. However, it has never been investigated whether measures of self-perception, like autonomy, is affected in Huntington's disease. OBJECTIVE: We investigated whether autonomy is affected in Huntington's disease and if the degree of autonomy is associated with motor function, neuropsychiatric symptoms, cognitive impairments, and apathy. METHODS: We included 44 premanifest and motor-manifest Huntington's disease gene expansion carriers and 19 controls. Autonomy was examined using two self-report questionnaires, the Autonomy-Connectedness Scale-30 and the Index of Autonomous Functioning. All participants were examined according to motor function, cognitive impairments, and neuropsychiatric symptoms, including apathy. RESULTS: Statistically significant differences were found between motor-manifest Huntington's disease gene expansion carriers and premanifest Huntington's disease gene expansion carriers or controls on two measures of autonomy. Between 25-38% of motor-manifest Huntington's disease gene expansion carriers scored significantly below the normal level on subscales of autonomy as compared to controls. One autonomy subscale was associated with apathy (r = -0.65), but not with other symptoms of Huntington's disease. CONCLUSION: This study provides evidence for impaired autonomy in individuals with Huntington's disease and an association between autonomy and apathy. The results underline the importance of maintaining patient autonomy and involvement in care throughout the disease.

Decreased CSF oxytocin relates to measures of social cognitive impairment in Huntington's disease patients.

OBJECTIVE: Huntington's disease (HD) is an inherited neurodegenerative disease with motor, cognitive and psychiatric symptoms. Non-motor symptoms like depression and altered social cognition are proposed to be caused by dysfunction of the hypothalamus. We measured the hypothalamic neuropeptide oxytocin in plasma and cerebrospinal fluid (CSF) in a cohort of HD gene expansion carriers (HDGECs), compared the levels to healthy HD family controls and correlated oxytocin levels to disease progression and social cognition. METHODS: We recruited 113 HDGECs and 33 controls. Psychiatric and cognitive symptoms were evaluated, and social cognition was assessed with the Emotion Hexagon test, Reading the Mind in the Eyes and The Awareness of Social Inference Test. The levels of oxytocin in CSF and blood were analyzed by radioimmunoassay. RESULTS: We found the level of oxytocin in CSF to be significantly lower by 33.5% in HDGECs compared to controls (p = 0.016). When dividing the HDGECs into groups with or without cognitive impairment, we found the oxytocin level to be significantly lower by 30.3% in the HDGECs with cognitive symptoms (p = 0.046). We found a statistically significant correlation between the level of oxytocin and scores on social cognition (Reading the Mind in the Eyes p = 0.0019; Emotion Hexagon test: p = 0.0062; The Awareness of Social Inference Test: p = 0.002). CONCLUSIONS: This is the first study to measure oxytocin in the CSF of HDGECs. We find that HDGECs have a significantly lower level of oxytocin compared to controls, and that the level of oxytocin may represent an objective and comparable measure that could be used as a state biomarker for impairment of social cognition. We suggest treatment trials to evaluate a potential effect of oxytocin on social cognition in HD.

Impairments of social cognition significantly predict the progression of functional decline in Huntington's disease: A 6-year follow-up study.

This study sought to investigate if there was a significant difference between the Huntington's Disease gene expansion carriers who were impaired on the cognitive domains, social cognition and executive functions. Also, it was investigated which of the cognitive domains could predict the decrease in total functional capacity over a 6-year follow-up period. Premanifest and motor-manifest Huntington's Disease gene expansion carriers (N = 98), were examined with a neurological and neuropsychological examination at Time 1 (year 2012-2013). Regression-based normative data was used to classify impairments on the two cognitive domains. Follow-up participants (N = 80) had their functional capacity reexamined at Time 2 (year 2018-2020), to examine which cognitive domain could predict the decrease in functional capacity over the 6-year follow-up. More than 50% of the participants were impaired on the domain of social cognition. These participants were significantly different from the participants who were impaired on executive functions. The motor function and impairments on social cognition significantly predicted the decline in functional capacity. The Emotion Hexagon test was the only significant social cognitive task, that predicted the decline in functional capacity. Social cognition includes unique and separate functions in Huntington's Disease, unaffected by executive functions. This study emphasizes the importance of regular assessment of social cognition in Huntington's Disease and the clinical relevance of impaired social cognitive function.

Intellectual Curiosity and Action Initiation are Subtypes of Apathy Affected in Huntington Disease Gene Expansion Carriers.

BACKGROUND: Apathy is a prevalent behavioral syndrome of Huntington disease (HD) that can result in severe loss of function for the individual with HD and substantial caregiver distress. Research-based evidence of apathy is characterized by methodological differences, and there is a deficiency in the evidence concerning the subtypes of apathy. OBJECTIVE: To characterize apathy in premanifest and motor-manifest HD gene expansion carriers and controls using the Short Problem Behaviors Assessment for Huntington's Disease (PBA-s) and the Lille Apathy Rating Scale (LARS). METHOD: We included 82 HD gene expansion carriers (premanifest and motor manifest) and 32 controls (Mini-Mental State Examination score ≥24 and Montreal Cognitive Assessment score ≥19) in the study. We quantified apathy using the PBA-s and the LARS and performed correlation analyses between the global LARS score and motor function, cytosine-adenine-guanine repeat length, cytosine-adenine-guanine Age Product score, and neuropsychiatric and cognitive symptoms. RESULTS: The motor-manifest HD gene expansion carriers scored significantly higher than the controls on the global score and the Intellectual Curiosity and Action Initiation subscales of the LARS. Apathy was present in 28% of the HD gene expansion carriers (including 7 premanifest). The apathetic participants had a significantly higher motor score, significantly higher scores on the neuropsychiatric instruments, and significantly lower cognitive scores compared with the controls. CONCLUSION: Apathy is a frequent syndrome that is found in individuals with HD. Apathy has a specific expression, with symptoms such as reduced initiation, voluntary actions, and interests, that might be related to the underlying neuropathology. Apathy is related to disease progression, neuropsychiatric symptoms, and cognitive impairments.

Endophenotypical drift in Huntington's disease: a 5-year follow-up study.

BACKGROUND: Huntington's disease (HD) is clinically characterized by progressing motor, cognitive and psychiatric symptoms presenting as varying phenotypes within these three major symptom domains. The disease is caused by an expanded CAG repeat tract in the huntingtin gene and the pathomechanism leading to these endophenotypes is assumed to be neurodegenerative. In 2012/2013 we recruited 107 HD gene expansion carriers (HDGECs) and examined the frequency of the three cardinal symptoms and in 2017/2018 we followed up 74 HDGECs from the same cohort to describe the symptom trajectories and individual drift between the endophenotypes as well as potential predictors of progression and remission. RESULTS: We found higher age to reduce the probability of improving on psychiatric symptoms; increasing disease burden score ((CAG-35.5) * age) to increase the risk of developing cognitive impairment; increasing disease burden score and shorter education to increase the risk of motor onset while lower disease burden score and higher Mini Mental State Examination increased the probability of remaining asymptomatic. We found 23.5% (N = 8) to improve from their psychiatric symptoms. CONCLUSIONS: There is no clear pattern in the development of or drift between endophenotypes. In contrast to motor and cognitive symptoms we find that psychiatric symptoms may resolve and thereby not entirely be caused by neurodegeneration. The probability of improving from psychiatric symptoms is higher in younger age and advocates for a potential importance of early treatment.

The good, the bad, and the average: Characterizing the relationship between face and object processing across the face recognition spectrum.

Face recognition skills vary considerably both in the normal population and in various clinical groups, and understanding the cognitive mechanisms contributing to this variability is important. In the present study, we investigate whether a group of good face recognizers (high performers; HPs) perform qualitatively differently from a control group on tests of face, object and word recognition, and also compare them to a group of developmental prosopagnosics (DPs). Through a series of experiments, we (i) examine whether HPs are better than control subjects in face and object recognition, (ii) investigate if any dissociations among face, object, and word processing tasks can be demonstrated in the HPs, and (iii) compare the performance of the HPs to a group of poor face recognizers namely a group of DPs. Data from this DP group have previously been reported, but the analyses presented here are new. We find that HPs were significantly better than matched control subjects on tests of face and object recognition including a reading task, but they did not show significantly larger inversion effects on typical tests of face processing (the CFMT and the CFPT). There was no evidence of dissociations between face and object processing in the HPs when compared to controls, indicating superior performance across visual domains. In the DP group, however, we found significant dissociations between face and object recognition performance on a group level, indicating that face processing is disproportionally affected. On this basis, we propose that superior face processing in HPs rely on more general cognitive or perceptual processes shared with object processing. Hence, while face processing in DPs seems qualitatively different from the normal population, there is no such difference between average and high performing face recognizers. Thus, what underlies superior face processing in HPs might also underlie their superior performance with other stimulus classes and might be conceived as a general factor in the visual domain, a VG-factor, akin to the G factor in intelligence.