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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, in which cognitive dysfunction is common, but poorly understood. This study aims to characterize the prevalence and patterns of cognitive dysfunction in SLE.
SLE patients (n = 95) and demographically matched healthy controls (n = 48) underwent cross-sectional cognitive testing using the 1-hr conventional neuropsychological test battery recommended by the American College of Rheumatology for use in SLE. We used standard deviations (SD) from the healthy control group to define impairment. For each cognitive test we compared SLE and control groups using independent samples t-tests (or alternatives when needed). We performed cluster analysis using a machine learning algorithm to look for patterns of cognitive dysfunction.
The SLE group performed significantly worse than healthy controls on every cognitive test. The largest differences were in the domains of verbal fluency, working memory and attention, while fine motor and psychomotor speed were the least affected domains. As expected, the prevalence of cognitive dysfunction varied depending on the SD cut-off used, with 49% of participants being >1.5 SD below the healthy control mean in at least two cognitive domains. Heat mapping showed variability in the pattern of dysfunction between individual patients and cluster analysis confirmed the presence of two clusters of patients, which were those significantly impaired versus those having preserved cognition.
Cognitive dysfunction is common in SLE but markedly heterogeneous across both cognitive domains and across the SLE group. Cluster analysis supports the use of a binary definition of cognitive dysfunction in SLE.
Discrepancies exist in reports of social cognition deficits in individuals with premanifest Huntington’s disease (HD); however, the reason for this variability has not been investigated. The aims of this study were to (1) evaluate group- and individual-level social cognitive performance and (2) examine intra-individual variability (dispersion) across social cognitive domains in individuals with premanifest HD.
Theory of mind (ToM), social perception, empathy, and social connectedness were evaluated in 35 individuals with premanifest HD and 29 healthy controls. Cut-off values beneath the median and 1.5 × the interquartile range below the 25th percentile (P25 – 1.5 × IQR) of healthy controls for each variable were established for a profiling method. Dispersion between social cognitive domains was also calculated.
Compared to healthy controls, individuals with premanifest HD performed worse on all social cognitive domains except empathy. Application of the profiling method revealed a large proportion of people with premanifest HD fell below healthy control median values across ToM (>80%), social perception (>57%), empathy (>54%), and social behaviour (>40%), with a percentage of these individuals displaying more pronounced impairments in empathy (20%) and ToM (22%). Social cognition dispersion did not differ between groups. No significant correlations were found between social cognitive domains and mood, sleep, and neurocognitive outcomes.
Significant group-level social cognition deficits were observed in the premanifest HD cohort. However, our profiling method showed that only a small percentage of these individuals experienced marked difficulties in social cognition, indicating the importance of individual-level assessments, particularly regarding future personalised treatments.
Objectives: Previous research has demonstrated an association between emotion recognition and apathy in several neurological conditions involving fronto-striatal pathology, including Parkinson’s disease and brain injury. In line with these findings, we aimed to determine whether apathetic participants with early Huntington’s disease (HD) were more impaired on an emotion recognition task compared to non-apathetic participants and healthy controls. Methods: We included 43 participants from the TRACK-HD study who reported apathy on the Problem Behaviours Assessment – short version (PBA-S), 67 participants who reported no apathy, and 107 controls matched for age, sex, and level of education. During their baseline TRACK-HD visit, participants completed a battery of cognitive and psychological tests including an emotion recognition task, the Hospital Depression and Anxiety Scale (HADS) and were assessed on the PBA-S. Results: Compared to the non-apathetic group and the control group, the apathetic group were impaired on the recognition of happy facial expressions, after controlling for depression symptomology on the HADS and general disease progression (Unified Huntington’s Disease Rating Scale total motor score). This was despite no difference between the apathetic and non-apathetic group on overall cognitive functioning assessed by a cognitive composite score. Conclusions: Impairment of the recognition of happy expressions may be part of the clinical picture of apathy in HD. While shared reliance on frontostriatal pathways may broadly explain associations between emotion recognition and apathy found across several patient groups, further work is needed to determine what relationships exist between recognition of specific emotions, distinct subtypes of apathy and underlying neuropathology. (JINS, 2019, 25, 453–461)
Objectives: People with Huntington’s disease (HD) experience poor social quality of life, relationship breakdown, and social withdrawal, which are mediated to some extent by socially debilitating neuropsychiatric symptoms, such as apathy and disinhibition. Social cognitive symptoms, such as impaired emotion recognition, also occur in HD, however, the extent of their association with these socially debilitating neuropsychiatric symptoms is unknown. Our study examined the relationship between emotion recognition and symptom ratings of apathy and disinhibition in HD. Methods: Thirty-two people with premanifest or symptomatic-HD completed Part 1 of The Awareness of Social Inference Test (TASIT), which is a facial emotion recognition task. In addition, we obtained severity ratings for apathy and disinhibition on the Frontal Systems Behavior Scale (FrSBe) from a close family member. Our analyses used motor symptom severity as a proxy for disease progression. Results: Emotion recognition performance was significantly associated with family-ratings of apathy, above and beyond their shared association with disease severity. We found a similar pattern for disinhibition ratings, which fell short of statistical significance. As expected, worse emotion recognition performance was correlated with higher severity in FrSBe symptom ratings. Conclusions: Our findings suggest that emotion recognition abilities relate to key socially debilitating neuropsychiatric symptoms in HD. Our results help to understand the functional significance of emotion recognition impairments in HD, and may have implications for the development of remediation programs aimed at improving patients’ social quality of life. (JINS, 2018, 24, 417–423)
Objectives: Deficits in the recognition of negative emotions emerge before clinical diagnosis in Huntington’s disease (HD). To address emotion recognition deficits, which have been shown in schizophrenia to be improved by computerized training, we conducted a study of the feasibility and efficacy of computerized training of emotion recognition in HD. Methods: We randomly assigned 22 individuals with premanifest or early symptomatic HD to the training or control group. The training group used a self-guided online training program, MicroExpression Training Tool (METT), twice weekly for 4 weeks. All participants completed measures of emotion recognition at baseline and post-training time-points. Participants in the training group also completed training adherence measures. Results: Participants in the training group completed seven of the eight sessions on average. Results showed a significant group by time interaction, indicating that METT training was associated with improved accuracy in emotion recognition. Conclusions: Although sample size was small, our study demonstrates that emotion recognition remediation using the METT is feasible in terms of training adherence. The evidence also suggests METT may be effective in premanifest or early-symptomatic HD, opening up a potential new avenue for intervention. Further study with a larger sample size is needed to replicate these findings, and to characterize the durability and generalizability of these improvements, and their impact on functional outcomes in HD. (JINS, 2017, 23, 314–321)
The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant.
To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance.
Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months.
Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity.
Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials.
Objectives: Visuospatial processing deficits have been reported in Huntington’s disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. Methods: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. Results: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation (“same”) was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. Conclusions: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595–608)
Disturbances of visual perception frequently accompany neurodegenerative disorders but have been little studied in Huntington's disease (HD) gene carriers. We used psychophysical tests to assess visual perception among individuals in the prediagnostic and early stages of HD. The sample comprised four groups, which included 201 nongene carriers (NG), 32 prediagnostic gene carriers with minimal neurological abnormalities (PD1); 20 prediagnostic gene carriers with moderate neurological abnormalities (PD2), and 36 gene carriers with diagnosed HD. Contrast sensitivity for stationary and moving sinusoidal gratings, and tests of form and motion discrimination, were used to probe different visual pathways. Patients with HD showed impaired contrast sensitivity for moving gratings. For one of the three contrast sensitivity tests, the prediagnostic gene carriers with greater neurological abnormality (PD2) also had impaired performance as compared with NG. These findings suggest that early stage HD disrupts visual functions associated with the magnocellular pathway. However, these changes are only observed in individuals diagnosed with HD or who are in the more symptomatic stages of prediagnostic HD. (JINS, 2008, 14, 446–453.)
Asperger's disorder (ASP), like other autism spectrum disorders,
is associated with altered responsiveness to social stimuli. This study
investigated learning and responsiveness to nonsocial, but motivational,
stimuli in ASP. We examined choice behavior and galvanic skin conductance
responses (SCRs) during the Iowa Gambling Task (IGT; Bechara et al., 1994) in 15 adolescents and young adults with ASP and
14 comparison subjects. We examined aspects of learning, attention to wins
and losses, and response style with a formal cognitive model, the
Expectancy–Valence Learning model (Busemeyer & Stout, 2002). The ASP group did not differ from the
comparison group in proportions of selections from advantageous decks.
However, ASP participants showed a distinct pattern of selection
characterized by frequent shifts between the four IGT decks, whereas
comparison participants developed clear deck preferences. SCR results
showed some evidence of reduced responsiveness in the ASP group during the
IGT. Results from the cognitive model indicated that, in contrast to the
comparison group, the ASP group's selections were less consistent
with the motivational significance they assigned to decks. Findings are
discussed in the context of the neurobiological substrates associated with
IGT performance (JINS, 2006, 12, 668–676.)
We examined the possible role of autonomic activity in
Huntington's disease (HD) during a risky decision making task.
Skin conductance responses (SCRs) of 15 HD participants and 16 healthy
controls were measured while they performed a computerized version of
the Simulated Gambling Task (SGT). The results replicated our previous
finding of a performance decrement in HD, and showed that HD was
associated with an altered pattern of SCRs during the risky decision
task. Specifically, the healthy controls produced increased SCRs
following selections from the disadvantageous decks and following
losing selections. In contrast, the SCRs of the HD group did not
differentiate between wins and losses. These findings indicate a
reduced impact of loss on decision-making processes under risky
conditions in HD. (JINS, 2004, 10,
In the clinical setting, Huntington's disease
is associated with problems in judgment and decision making,
however, the extent of these problems and their association
with clinical characteristics have not been assessed. Recently,
a laboratory-based simulated gambling task has been used
to quantify similar decision-making deficits in ventromedial
frontal lobe damaged participants. We hypothesized that
participants with Huntington's disease (HD) would
show deficits on this gambling task. For this study, 14
HD participants were asked to make 100 selections from
four decks of cards with varied payoffs in order to maximize
winnings of play money. They were compared to 22 participants
with Parkinson's disease (PD) and 33 healthy controls.
After an initial period in which participants had to learn
contingencies of the decks, the HD group made fewer advantageous
selections than the PD and control groups. In HD, the number
of advantageous selections in the gambling task was correlated
with measures of memory and conceptualization but not disinhibition.
Thus, people with HD may have had difficulties learning
or remembering win/loss contingencies of the decks, or
they may have failed to consistently take these into account
in their card selections. These findings are consistent
with current models of frontal-subcortical brain circuits
and behavior. (JINS, 2001, 7, 92–101.)
Psychotic symptoms are common in Alzheimer's
disease (AD) and clinicoanatomical and neuropsychological
evidence indicate an association between these symptoms
and frontal lobe dysfunction. Neurobehaviors associated
with frontal dysfunction were assessed in Alzheimer's
disease (AD) patients with (n = 20) and without
psychotic symptoms (n = 21) matched for mean age,
education, gender, and dementia severity. The Frontal Lobe
Personality Scale (FLOPs) was completed by patient caregivers
to measure behaviors typically associated with frontal
dysfunction. Findings indicated that AD patients with psychotic
symptoms exhibited significantly greater neurobehavioral
dysfunction (FLOPs M = 130.69, SD = 24.70)
than AD patients without psychotic symptoms (FLOPs M =
111.10, SD = 25.83). Subscale analyses indicated that
psychotic AD patients were more disinhibited (M = 28.28,
SD = 7.54) than patients without psychotic symptoms
(M = 20.92, SD = 4.9). Findings are consistent
with and contribute to previous neuropsychological and
clinicoanatomical research suggesting increased frontal
dysfunction in AD with psychotic symptoms and lend additional
empirical support to subtyping AD based on the presence
of psychotic symptoms. Furthermore, findings provide preliminary
evidence indicating which specific type of neurobehavioral
abnormalities are related to the presence of distressing psychotic
symptoms. (JINS, 2000, 6, 815–820.)
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