Visuomotor integration deficits are common to familial and sporadic preclinical Alzheimer's disease.

We investigated whether subtle visuomotor deficits were detectable in familial and sporadic preclinical Alzheimer's disease. A circle-tracing task-with direct and indirect visual feedback, and dual-task subtraction-was completed by 31 individuals at 50% risk of familial Alzheimer's disease (19 presymptomatic mutation carriers; 12 non-carriers) and 390 cognitively normal older adults (members of the British 1946 Birth Cohort, all born during the same week; age range at assessment = 69-71 years), who also underwent ß-amyloid-PET/MRI to derive amyloid status (positive/negative), whole-brain volume and white matter hyperintensity volume. We compared preclinical Alzheimer's groups against controls cross-sectionally (mutation carriers versus non-carriers; amyloid-positive versus amyloid-negative) on speed and accuracy of circle-tracing and subtraction. Mutation carriers (mean 7 years before expected onset) and amyloid-positive older adults traced disproportionately less accurately than controls when visual feedback was indirect, and were slower at dual-task subtraction. In the older adults, the same pattern of associations was found when considering amyloid burden as a continuous variable (Standardized Uptake Value Ratio). The effect of amyloid was independent of white matter hyperintensity and brain volumes, which themselves were associated with different aspects of performance: greater white matter hyperintensity volume was also associated with disproportionately poorer tracing accuracy when visual feedback was indirect, whereas larger brain volume was associated with faster tracing and faster subtraction. Mutation carriers also showed evidence of poorer tracing accuracy when visual feedback was direct. This study provides the first evidence of visuomotor integration deficits common to familial and sporadic preclinical Alzheimer's disease, which may precede the onset of clinical symptoms by several years.

Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington's Disease.

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).

The potential of composite cognitive scores for tracking progression in Huntington's disease.

BACKGROUND: Composite scores derived from joint statistical modelling of individual risk factors are widely used to identify individuals who are at increased risk of developing disease or of faster disease progression. OBJECTIVE: We investigated the ability of composite measures developed using statistical models to differentiate progressive cognitive deterioration in Huntington's disease (HD) from natural decline in healthy controls. METHODS: Using longitudinal data from TRACK-HD, the optimal combinations of quantitative cognitive measures to differentiate premanifest and early stage HD individuals respectively from controls was determined using logistic regression. Composite scores were calculated from the parameters of each statistical model. Linear regression models were used to calculate effect sizes (ES) quantifying the difference in longitudinal change over 24 months between premanifest and early stage HD groups respectively and controls. ES for the composites were compared with ES for individual cognitive outcomes and other measures used in HD research. The 0.632 bootstrap was used to eliminate biases which result from developing and testing models in the same sample. RESULTS: In early HD, the composite score from the HD change prediction model produced an ES for difference in rate of 24-month change relative to controls of 1.14 (95% CI: 0.90 to 1.39), larger than the ES for any individual cognitive outcome and UHDRS Total Motor Score and Total Functional Capacity. In addition, this composite gave a statistically significant difference in rate of change in premanifest HD compared to controls over 24-months (ES: 0.24; 95% CI: 0.04 to 0.44), even though none of the individual cognitive outcomes produced statistically significant ES over this period. CONCLUSIONS: Composite scores developed using appropriate statistical modelling techniques have the potential to materially reduce required sample sizes for randomised controlled trials.

Investigating facial affect processing in psychosis: a study using the Comprehensive Affective Testing System.

Facial affect processing (FAP) deficits in schizophrenia (SZ) and bipolar disorder (BD) have been widely reported; although effect sizes vary across studies, and there are limited direct comparisons of the two groups. Further, there is debate as to the influence of both psychotic and mood symptoms on FAP. This study aimed to address these limitations by recruiting groups of psychosis patients with either a diagnosis of SZ or BD and comparing them to healthy controls (HC) on a well validated battery of four FAP subtests: affect discrimination, name affect, select affect and match affect. Overall, both groups performed more poorly than controls in terms of accuracy. In SZ, this was largely driven by impairments on three of the four subtests. The BD patients showed impaired performance specifically on the match affect subtest, a task that had a high cognitive load. FAP performance in the psychosis patients was correlated with severity of positive symptoms and mania. This study confirmed that FAP deficits are a consistent finding in SZ that occur independent of task specific methodology; whilst FAP deficits in BD are more subtle. Further work in this group is needed to replicate these results.

Investigating affective prosody in psychosis: a study using the Comprehensive Affective Testing System.

Affective prosody is substantially impaired in schizophrenia, yet little is known about affective prosody in bipolar disorder (BD). The aim of this study was to examine affective prosody performance in schizophrenia, schizoaffective disorder and BD on a newly released standardised assessment to further our understanding of BD performance. Fifty-four schizophrenia, 11 schizoaffective and 43 BD patients were compared with 112 healthy controls (HC) on four affective prosody subtests of the Comprehensive Affective Testing System (CATS). Schizophrenia patients showed a 10% reduction in accuracy on two subtests compared to HC. BD showed a trend for performance intermediary to schizophrenia and HC; and schizoaffective patients performed more like HC on these four affective prosody measures. Severity of current auditory hallucination, across all patients, was related to task performance on three of the measures. These data confirm that schizophrenia and BD have reduced affective prosody performance, with deficits in BD being less pronounced than schizophrenia. The schizoaffective results in this study should be interpreted with caution due to small sample size.

Evaluation of longitudinal 12 and 24 month cognitive outcomes in premanifest and early Huntington's disease.

BACKGROUND: Deterioration of cognitive functioning is a debilitating symptom in many neurodegenerative diseases, such as Huntington's disease (HD). To date, there are no effective treatments for the cognitive problems associated with HD. Cognitive assessment outcomes will have a central role in the efforts to develop treatments to delay onset or slow the progression of the disease. The TRACK-HD study was designed to build a rational basis for the selection of cognitive outcomes for HD clinical trials. METHODS: There were a total of 349 participants, including controls (n=116), premanifest HD (n=117) and early HD (n=116). A standardised cognitive assessment battery (including nine cognitive tests comprising 12 outcome measures) was administered at baseline, and at 12 and 24 months, and consisted of a combination of paper and pencil and computerised tasks selected to be sensitive to cortical-striatal damage or HD. Each cognitive outcome was analysed separately using a generalised least squares regression model. Results are expressed as effect sizes to permit comparisons between tasks. RESULTS: 10 of the 12 cognitive outcomes showed evidence of deterioration in the early HD group, relative to controls, over 24 months, with greatest sensitivity in Symbol Digit, Circle Tracing direct and indirect, and Stroop word reading. In contrast, there was very little evidence of deterioration in the premanifest HD group relative to controls. CONCLUSIONS: The findings describe tests that are sensitive to longitudinal cognitive change in HD and elucidate important considerations for selecting cognitive outcomes for clinical trials of compounds aimed at ameliorating cognitive decline in HD.

Visual Working Memory Impairment in Premanifest Gene-Carriers and Early Huntington's Disease.

Working memory deficits have been found in Huntington's disease (HD) and in a small group of premanifest (PreHD) gene-carriers. However, the nature and extent of these deficits are unknown. In a large cross-sectional study, we aimed to determine the degree of visuospatial working memory dysfunction across multiple stages of HD. Specifically, visuospatial working memory capacity and response times across various degrees of difficulty were examined, as well as the relationship between visuospatial working memory and motor dysfunction. We examined 62 PreHD-A gene-carriers (>10.8 years from estimated disease onset), 58 PreHD-B gene-carriers (<10.8 years from estimated disease onset), 77 stage-1 HD patients (HD1), 44 stage-2 HD patients (HD2), and 122 healthy controls. Participants viewed coloured squares (in sets of 3, 5 and 7) on a screen and were to decide whether on a subsequent screen the encircled square has changed colour. Accuracy and response times were recorded. Compared to controls, significant group differences in visuospatial working memory capacity (accuracy) were seen in PreHD-B, HD1 and HD2 groups across the difficulty levels. Significant group differences on response times were found for all groups (PreHD-A to HD2) compared to controls; the most difficult level producing the only group difference in speed between PreHD-A and controls. Accuracy and speed were positively correlated only in the HD groups. These findings suggest that visuospatial working memory impairments are detectable in both premanifest and manifest HD; the manifest HD showed evidence for a "worse-worse phenomenon" whereby reductions were present in both motor speed and accuracy.

Is semantic processing impaired in individuals with high schizotypy?

Semantic processing deficits are present in schizophrenia. However, this research has often been criticized for methodological artifacts and confounds, including long hospitalizations and medication of patient samples. Utilizing high schizotypes (psychosis-prone individuals) can overcome these confounds. Previously, similar deficits have been reported in high schizotypes and schizophrenia on semantic priming tasks. In contrast to schizophrenia research, no other types of semantic processing have been examining in high schizotypes. Semantic processing is multifaceted, thus, deficits on semantic priming can not answer whether high schizotypes have difficulty with explicit semantic processing, that is, on tasks that require the conscious recollection of semantic information. In the current study, 24 high and 30 low scorers on the O-LIFE schizotypy scale were administered a battery of semantic processing measures. The high schizotypy group did not show global semantic processing impairments (as has been shown in schizophrenia), only impairments on a task designed to examine subtle categorization processing. Such deficits can be equated to those found on semantic priming tasks, in that both require quick and accurate access to semantic networks.

Open courseware and shared knowledge in higher education.

Most college and university campuses in the United States and much of the developed world today maintain one, two, or several learning management systems (LMSs), which are courseware products that provide students and faculty with Web-based tools to manage course-related applications. Since the mid-1990s, two predominant models of Web courseware management systems have emerged: commercial and noncommercial. Some of the commercial products available today were created in academia as noncommercial but have since become commercially encumbered. Other products remain noncommercial but are struggling to survive in a world of fierce commercial competition. This article argues for an ethics of pedagogy in higher education that would be based on the guiding assumptions of the non-proprietary, peer-to-peer, open-source software movement.