The Effects of Previous Error and Success in Alzheimer's Disease and Mild Cognitive Impairment.

This work investigated in Alzheimer's disease dementia (AD), whether the probability of making an error on a task (or a correct response) was influenced by the outcome of the previous trials. We used the antisaccade task (AST) as a model task given the emerging consensus that it provides a promising sensitive and early biological test of cognitive impairment in AD. It can be employed equally well in healthy young and old adults, and in clinical populations. This study examined eye-movements in a sample of 202 participants (42 with dementia due to AD; 65 with mild cognitive impairment (MCI); 95 control participants). The findings revealed an overall increase in the frequency of AST errors in AD and MCI compared to the control group, as predicted. The errors on the current trial increased in proportion to the number of consecutive errors on the previous trials. Interestingly, the probability of errors was reduced on the trials that followed a previously corrected error, compared to the trials where the error remained uncorrected, revealing a level of adaptive control in participants with MCI or AD dementia. There was an earlier peak in the AST distribution of the saccadic reaction times for the inhibitory errors in comparison to the correct saccades. These findings revealed that the inhibitory errors of the past have a negative effect on the future performance of healthy adults as well as people with a neurodegenerative cognitive impairment.

Feasibility and Acceptability of Computerised Cognitive Training of Everyday Cognition in Parkinson's Disease.

OBJECTIVES: We piloted a computerised cognitive training battery in a group of participants with Parkinson's disease without dementia to investigate the relevance of the training to daily life and the feasibility and the acceptability of the tasks. Previous studies of CT have had limited success in the benefits of training, extending to improvements in everyday function. By taking a pragmatic approach and targeting training to the cognitive skills affected by Parkinson's disease (planning, attention, and recollection), whilst using tasks that emulated real-life scenarios, we sought to understand whether participants perceived the training to be effective and to identify the elements of the training that elicited beneficial effects. METHODS: Four participants completed a cognitive training session comprising three distinct tasks 5 days a week over two weeks. Participants completed baseline questionnaires examining health-related quality of life, everyday cognition, and apathy before the training period, after the last session, and two weeks after the last session. An interview was held after participants had completed the training. RESULTS: The findings indicated that participants felt the training was acceptable, enhanced their awareness, and encouraged them to monitor their thinking abilities. The group interview indicated that the training was feasible; participants felt the tasks had potential to improve everyday performance, but more supporting information should be provided to facilitate this transfer. Responses to the questionnaires reflected these findings, indicating improvement for some participants' cognition and quality of life. Objective measures supported the subjective reports; there were improvements in some but not all domains. Performance on the planning and recollection tasks improved over the training period, and the evidence for improvement on the attention task was mixed. CONCLUSION: This study has found that pragmatic computer-based training with real-life outcomes is both feasible and acceptable and should be evaluated more extensively using controlled methods.

Can you detect early dementia from an email? A proof of principle study of daily computer use to detect cognitive and functional decline.

OBJECTIVE: To determine whether multiple computer use behaviours can distinguish between cognitively healthy older adults and those in the early stages of cognitive decline, and to investigate whether these behaviours are associated with cognitive and functional ability. METHODS: Older adults with cognitive impairment (n = 20) and healthy controls (n = 24) completed assessments of cognitive and functional abilities and a series of semi-directed computer tasks. Computer use behaviours were captured passively using bespoke software. RESULTS: The profile of computer use behaviours was significantly different in cognitively impaired compared with cognitively healthy control participants including more frequent pauses, slower typing, and a higher proportion of mouse clicks. These behaviours were significantly associated with performance on cognitive and functional assessments, in particular, those related to memory. CONCLUSION: Unobtrusively capturing computer use behaviours offers the potential for early detection of neurodegeneration in non-clinical settings, which could enable timely interventions to ultimately improve long-term outcomes.

Cognitive Impairment in Chronic Obstructive Pulmonary Disease and Chronic Heart Failure: A Systematic Review and Meta-analysis of Observational Studies.

BACKGROUND: Cognitive impairment is common in people living with chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF); however, accurate estimates of prevalence are lacking. To date, there are no meta-analyses that have specifically investigated prevalence of mild cognitive impairment (MCI) in this particular population. Our aim was to undertake a systematic review and apply meta-analytic methods to estimate the prevalence of MCI and any cognitive impairment (ACI) in people with COPD and CHF. METHODS: We identified relevant studies for COPD and CHF by searching the published literature from inception to February 2016 using the MEDLINE and Web of Science databases. Studies were included if they documented the prevalence of MCI and/or cognitive impairment for COPD and CHF patients without dementia. RESULTS: Seventeen studies including people with CHF (n = 29,456) and 14 studies including people with COPD (n = 23,116) were included. The pooled mean age for COPD was 66.3 years and for CHF, 75.6 years. The pooled prevalence of MCI in the COPD was 25% (95% CI: 23%, 42%) and ACI, 32% (95% CI: 18%, 38%). Correspondingly, the pooled prevalence of MCI in those with CHF was 32% (95% CI: 22%, 43%) and ACI, 31% (95% CI: 23%, 40%). CONCLUSIONS: One in 4 people with COPD and 1 in 3 people with CHF had MCI, respectively. The overall prevalence of ACI for COPD was 32% and for CHF, 31%. Future work should consider ways of detecting, managing, or improving cognitive function and other cognition-related outcomes in this group of people.

Lithium in patients with amyotrophic lateral sclerosis (LiCALS): a phase 3 multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Lithium has neuroprotective effects in cell and animal models of amyotrophic lateral sclerosis (ALS), and a small pilot study in patients with ALS showed a significant effect of lithium on survival. We aimed to assess whether lithium improves survival in patients with ALS. METHODS: The lithium carbonate in amyotrophic lateral sclerosis (LiCALS) trial is a randomised, double-blind, placebo-controlled trial of oral lithium taken daily for 18 months in patients with ALS. Patients aged at least 18 years who had ALS according to the revised El Escorial criteria, had disease duration between 6 and 36 months, and were taking riluzole were recruited from ten centres in the UK. Patients were randomly assigned (1:1) to receive either lithium or matched placebo tablets. Randomisation was via an online system done at the level of the individual by block randomisation with randomly varying block sizes, stratified by study centre and site of disease onset (limb or bulbar). All patients and assessing study personnel were masked to treatment assignment. The primary endpoint was the rate of survival at 18 months and was analysed by intention to treat. This study is registered with Eudract, number 2008-006891-31. FINDINGS: Between May 26, 2009, and Nov 10, 2011, 243 patients were screened, 214 of whom were randomly assigned to receive lithium (107 patients) or placebo (107 patients). Two patients discontinued treatment and one died before the target therapeutic lithium concentration could be achieved. 63 (59%) of 107 patients in the placebo group and 54 (50%) of 107 patients in the lithium group were alive at 18 months. The survival functions did not differ significantly between groups (Mantel-Cox log-rank χ(2) on 1 df=1·64; p=0·20). After adjusting for study centre and site of onset using logistic regression, the relative odds of survival at 18 months (lithium vs placebo) was 0·71 (95% CI 0·40-1·24). 56 patients in the placebo group and 61 in the lithium group had at least one serious adverse event. INTERPRETATION: We found no evidence of benefit of lithium on survival in patients with ALS, but nor were there safety concerns, which had been identified in previous studies with less conventional designs. This finding emphasises the importance of pursuing adequately powered trials with clear endpoints when testing new treatments. FUNDING: The Motor Neurone Disease Association of Great Britain and Northern Ireland.

Automatic video monitoring system for assessment of Alzheimer's disease symptoms.

In order to fully capture the complexity of the behavioural, functioning and cognitive disturbances in Alzheimer Disease (AD) and related disorders information and communication techniques (ICT), could be of interest. This article presents using 3 clinical cases the feasibility results of an automatic video monitoring system aiming to assess subjects involved in a clinical scenario. METHOD AND POPULATION: The study was conducted in an observation room equipped with everyday objects for use in activities of daily living. The overall aim of the clinical scenario was to enable the participants to undertake a set of daily tasks that could realistically be achieved in the setting of the observation room. The scenario was divided in three steps covering basic to more complex activities: (1) Directed activities, (2) Semi-directed activities, (3) Undirected ("free") activities. The assessment of each participant of the study was done with an automatic video monitoring system composed of a vision component and an event recognition component. The feasibility study involved three participants: two AD patients and one elderly control participant. RESULTS: The first result of the study was to demonstrate the feasibility of this new assessment method from both the patient and the technical points of view. During the first step the control participant performed all these activities faster than the two AD participants. During the second step of the scenario AD participants were not able to follow the correct order of the tasks and even omitted some of them. Finally during the last step of the scenario devoted to free activities the control participant chose one of the proposed activities (reading) and undertook this activity for almost the entire duration. In contrast, the two AD participants had more difficulties choosing one of the suggested activities and were not able to undertake any one activity in a sustained manner. DISCUSSION: The automatic video monitoring system presented here analyzes human behaviours and looks for changes in activity through the detection of the presence of people and their movements in real time. Once the technique has been standardized, it could significantly enhance the assessment of AD patients in both clinical and clinical trial settings as well as providing further information regarding patient frailty that could enhance their safety and ease caregiver burden.

Neuropsychiatry of Huntington's disease and other basal ganglia disorders.

Degenerative diseases of the basal ganglia, such as Huntington's disease (HD), Parkinson's disease, and Wilson's disease, are characterized by motor, cognitive, and psychiatric manifestations. HD, in particular, can be considered a paradigmatic neuropsychiatric disorder that has all three components of the "Triadic Syndromes": dyskinesia, dementia, and depression. The authors examine the phenomenology, prevalence, and management of psychiatric disturbances occurring in diseases of the basal ganglia. They address psychiatric conditions such as depression, mania, psychosis, obsessive-compulsive disorders, aggression, irritability, apathy, sexual disorders, and delirium, discussing subtleties of diagnosis, and making reference to more unusual disorders of the basal ganglia, such as postencephalitic parkinsonism and Fahr's disease.

Treatment of the psychiatric manifestations of Huntington's disease: a review of the literature.

OBJECTIVE: To review the clinical management of the psychiatric aspects of Huntington's disease (HD), namely the mood disorders, psychotic disorders, anxiety symptoms, sleep disorders, disorders of sexuality, and the behavioural changes of apathy, irritability, and aggression. Emphasis is on pharmacologic and psychotherapeutic intervention strategies. In addition, the role of psychiatric intervention in presymptomatic testing is explored. METHOD: English language literature on the pharmacologic and psychotherapeutic management of the psychiatric manifestations of HD between 1976 and 1996 was critically reviewed. RESULTS: Few sound studies address the clinical management of the psychiatric aspects of HD; thus, only the broadest conclusions can be drawn. Pharmacologic strategies for the treatment of psychiatric aspects of HD were organized according to the therapeutic agent and class, and psychotherapeutic strategies were discussed. CONCLUSION: The clinical management of the psychiatric manifestations of HD requires much more complete and systematic study before any definite conclusions as to efficacy of various approaches can be drawn.