Re-evaluating patient communication and care in angiographically negative subarachnoid hemorrhage: Balancing realism and optimism.

Angiographically negative subarachnoid hemorrhage (anSAH) has traditionally been considered a benign condition, mainly because of favorable outcomes in the acute stage in comparison to the often negative acute outcomes of aneurysmal subarachnoid hemorrhage. However, a growing body of research in recent years shows that anSAH often leads to cognitive impairments, emotional distress, and difficulties in resuming work or other daily life activities. Therefore, in this position paper, we call for a change in neurological care and a shift in patient communication, emphasizing the importance of addressing patient needs and fostering realistic expectations rather than solely focusing on the benign nature of the condition.

A Systematic Review of Cognition in Cervical Dystonia.

Growing evidence points to a spectrum of non-motor symptoms, including cognitive difficulties that have a greater impact on functional outcomes and quality of life than motor symptoms in cervical dystonia (CD). Some cognitive impairments have been reported; however, findings are inconsistent, and described across mixed groups of dystonia. The current review aimed to examine the evidence for cognitive impairments in CD. MEDLINE, EMBASE, PsychINFO and Web of Science databases were searched. Studies were included if they met the following criteria (i) cross-sectional or longitudinal studies of adults with CD, (ii) where the results of standardised measures of cognitive or neuropsychological function in any form were assessed and reported, (iii) results compared to a control group or normative data, and (iv) were published in English. Results are presented in a narrative synthesis. Twenty studies were included. Subtle difficulties with general intellectual functioning, processing speed, verbal memory, visual memory, visuospatial function, executive function, and social cognition were identified while language, and attention and working memory appear to be relatively spared. Several methodological limitations were identified that should be considered when interpreting the evidence to describe a specific profile of cognitive impairment in CD. Clinical and research implications are discussed.

Functional network dynamics revealed by EEG microstates reflect cognitive decline in amyotrophic lateral sclerosis.

Recent electroencephalography (EEG) studies have shown that patterns of brain activity can be used to differentiate amyotrophic lateral sclerosis (ALS) and control groups. These differences can be interrogated by examining EEG microstates, which are distinct, reoccurring topographies of the scalp's electrical potentials. Quantifying the temporal properties of the four canonical microstates can elucidate how the dynamics of functional brain networks are altered in neurological conditions. Here we have analysed the properties of microstates to detect and quantify signal-based abnormality in ALS. High-density resting-state EEG data from 129 people with ALS and 78 HC were recorded longitudinally over a 24-month period. EEG topographies were extracted at instances of peak global field power to identify four microstate classes (labelled A-D) using K-means clustering. Each EEG topography was retrospectively associated with a microstate class based on global map dissimilarity. Changes in microstate properties over the course of the disease were assessed in people with ALS and compared with changes in clinical scores. The topographies of microstate classes remained consistent across participants and conditions. Differences were observed in coverage, occurrence, duration, and transition probabilities between ALS and control groups. The duration of microstate class B and coverage of microstate class C correlated with lower limb functional decline. The transition probabilities A to D, C to B and C to B also correlated with cognitive decline (total ECAS) in those with cognitive and behavioural impairments. Microstate characteristics also significantly changed over the course of the disease. Examining the temporal dependencies in the sequences of microstates revealed that the symmetry and stationarity of transition matrices were increased in people with late-stage ALS. These alterations in the properties of EEG microstates in ALS may reflect abnormalities within the sensory network and higher-order networks. Microstate properties could also prospectively predict symptom progression in those with cognitive impairments.

Cognitive and neuropsychiatric endophenotypes in amyotrophic lateral sclerosis.

First- and second-degree relatives of people with amyotrophic lateral sclerosis report higher rates of neuropsychiatric disorders, indicating that risk genes may be pleiotropic, causing multiple phenotypes within kindreds. Such phenotypes may constitute a disease endophenotype that associates with disease liability. We have directly investigated cognitive functioning and neuropsychiatric traits among relatives of people with amyotrophic lateral sclerosis to identify potential endophenotypes of the disease. In a family-based, cross-sectional study design, first- and second-degree relatives of people with amyotrophic lateral sclerosis (n = 149) were compared to controls (n = 60) using an in-depth neuropsychological and neuropsychiatric assessment. Subgroup analyses examined the effect of family history and C9orf72 repeat expansion status (n = 16 positive carriers). Relatives of people with amyotrophic lateral sclerosis had lower scores on executive functioning, language and memory tasks compared to controls, with large effect sizes observed on object naming (d = 0.91, P = 0.00001) and phonemic verbal fluency (d = 0.81, P = 0.0003). Relatives also had higher autism quotient attention to detail traits (d = -0.52, P = 0.005), lower conscientiousness (d = 0.57, P = 0.003) and lower openness to experience personality traits (d = 0.54, P = 0.01) than controls. These effects were typically larger in relatives of people with familial, rather than sporadic, amyotrophic lateral sclerosis and were present in both gene carrier and non-carrier relatives of probands with a C9orf72 repeat expansion. Poorer phonemic fluency and object naming, along with autism and personality traits, are more frequent in relatives of people with amyotrophic lateral sclerosis. Among kindreds carrying the C9orf72 repeat expansion, these traits were identified in relatives regardless of their carrier status, suggesting the presence of a disease-associated endophenotype that is not exclusively mediated by the C9orf72 expansion.

Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries.

Importance: Diagnostic incidence data for syndromes associated with frontotemporal lobar degeneration (FTLD) in multinational studies are urgent in light of upcoming therapeutic approaches. Objective: To assess the incidence of FTLD across Europe. Design, Setting, and Participants: The Frontotemporal Dementia Incidence European Research Study (FRONTIERS) was a retrospective cohort study conducted from June 1, 2018, to May 31, 2019, using a population-based registry from 13 tertiary FTLD research clinics from the UK, the Netherlands, Finland, Sweden, Spain, Bulgaria, Serbia, Germany, and Italy and including all new FTLD-associated cases during the study period, with a combined catchment population of 11 023 643 person-years. Included patients fulfilled criteria for the behavioral variant of frontotemporal dementia (BVFTD), the nonfluent variant or semantic variant of primary progressive aphasia (PPA), unspecified PPA, progressive supranuclear palsy, corticobasal syndrome, or frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS). Data were analyzed from July 19 to December 7, 2021. Main Outcomes and Measures: Random-intercept Poisson models were used to obtain estimates of the European FTLD incidence rate accounting for geographic heterogeneity. Results: Based on 267 identified cases (mean [SD] patient age, 66.70 [9.02] years; 156 males [58.43%]), the estimated annual incidence rate for FTLD in Europe was 2.36 cases per 100 000 person-years (95% CI, 1.59-3.51 cases per 100 000 person-years). There was a progressive increase in FTLD incidence across age, reaching its peak at the age of 71 years, with 13.09 cases per 100 000 person-years (95% CI, 8.46-18.93 cases per 100 000 person-years) among men and 7.88 cases per 100 000 person-years (95% CI, 5.39-11.60 cases per 100 000 person-years) among women. Overall, the incidence was higher among men (2.84 cases per 100 000 person-years; 95% CI, 1.88-4.27 cases per 100 000 person-years) than among women (1.91 cases per 100 000 person-years; 95% CI, 1.26-2.91 cases per 100 000 person-years). BVFTD was the most common phenotype (107 cases [40.07%]), followed by PPA (76 [28.46%]) and extrapyramidal phenotypes (69 [25.84%]). FTD-ALS was the rarest phenotype (15 cases [5.62%]). A total of 95 patients with FTLD (35.58%) had a family history of dementia. The estimated number of new FTLD cases per year in Europe was 12 057. Conclusions and Relevance: The findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.

Resting-state EEG reveals four subphenotypes of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a devastating disease characterized primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. Amyotrophic lateral sclerosis is both clinically and biologically heterogeneous. Subgrouping is currently undertaken using clinical parameters, such as site of symptom onset (bulbar or spinal), burden of disease (based on the modified El Escorial Research Criteria) and genomics in those with familial disease. However, with the exception of genomics, these subcategories do not take into account underlying disease pathobiology, and are not fully predictive of disease course or prognosis. Recently, we have shown that resting-state EEG can reliably and quantitatively capture abnormal patterns of motor and cognitive network disruption in amyotrophic lateral sclerosis. These network disruptions have been identified across multiple frequency bands, and using measures of neural activity (spectral power) and connectivity (comodulation of activity by amplitude envelope correlation and synchrony by imaginary coherence) on source-localized brain oscillations from high-density EEG. Using data-driven methods (similarity network fusion and spectral clustering), we have now undertaken a clustering analysis to identify disease subphenotypes and to determine whether different patterns of disruption are predictive of disease outcome. We show that amyotrophic lateral sclerosis patients (n = 95) can be subgrouped into four phenotypes with distinct neurophysiological profiles. These clusters are characterized by varying degrees of disruption in the somatomotor (α-band synchrony), frontotemporal (ß-band neural activity and γl-band synchrony) and frontoparietal (γl-band comodulation) networks, which reliably correlate with distinct clinical profiles and different disease trajectories. Using an in-depth stability analysis, we show that these clusters are statistically reproducible and robust, remain stable after reassessment using a follow-up EEG session, and continue to predict the clinical trajectory and disease outcome. Our data demonstrate that novel phenotyping using neuroelectric signal analysis can distinguish disease subtypes based exclusively on different patterns of network disturbances. These patterns may reflect underlying disease neurobiology. The identification of amyotrophic lateral sclerosis subtypes based on profiles of differential impairment in neuronal networks has clear potential in future stratification for clinical trials. Advanced network profiling in amyotrophic lateral sclerosis can also underpin new therapeutic strategies that are based on principles of neurobiology and designed to modulate network disruption.

Patterns of Language Impairment in Early Amyotrophic Lateral Sclerosis.

OBJECTIVE: To investigate the incidence and nature of language change and its relationship to executive dysfunction in a population-based incident amyotrophic lateral sclerosis (ALS) sample, with the hypothesis that patterns of frontotemporal involvement in early ALS extend beyond areas of executive control to regions associated with language processing. METHODS: One hundred seventeen population-based incident ALS cases without dementia and 100 controls matched by age, sex, and education were included in the study. A detailed assessment of language processing including lexical processing, word spelling, word reading, word naming, semantic processing, and syntactic/grammatical processing was undertaken. Executive domains of phonemic verbal fluency, working memory, problem-solving, cognitive flexibility, and social cognition were also evaluated. RESULTS: Language processing was impaired in this incident cohort of individuals with ALS, with deficits in the domains of word naming, orthographic processing, and syntactic/grammatical processing. Conversely, phonological lexical processing and semantic processing were spared. Although executive dysfunction accounted in part for impairments in grammatical and orthographic lexical processing, word spelling, reading, and naming, primary language deficits were also present. CONCLUSIONS: Language impairment is characteristic of ALS at early stages of the disease and can develop independently of executive dysfunction, reflecting selective patterns of frontotemporal involvement at disease onset. Language change is therefore an important component of the frontotemporal syndrome associated with ALS.

StrokeCog Markov Model: Projected Prevalent and Incident Cases of Stroke and Poststroke Cognitive Impairment to 2035 in Ireland.

BACKGROUND AND PURPOSE: Cognitive impairment no dementia (CIND) and dementia are common stroke outcomes, with significant health and societal implications for aging populations. These outcomes are not included in current epidemiological models. We aimed to develop an epidemiological model to project incidence and prevalence of stroke, poststroke CIND and dementia, and life expectancy, in Ireland to 2035, informing policy and service planning. METHODS: We developed a probabilistic Markov model (the StrokeCog model) applied to the Irish population aged 40 to 89 years to 2035. Data sources included official population and hospital-episode statistics, longitudinal cohort studies, and published estimates. Key assumptions were varied in sensitivity analysis. Results were externally validated against independent sources. The model tracks poststroke progression into health states characterized by no cognitive impairment, CIND, dementia, disability, stroke recurrence, and death. RESULTS: We projected 69 051 people with prevalent stroke in Ireland in 2035 (22.0 per 1000 population [95% CI, 20.8-23.1]), with 25 274 (8.0 per 1000 population [95% CI, 7.1-9.0]) of those projected to have poststroke CIND, and 12 442 having poststroke dementia (4.0 per 1000 population [95% CI, 3.2-4.8]). We projected 8725 annual incident strokes in 2035 (2.8 per 1000 population [95% CI, 2.7-2.9]), with 3832 of these having CIND (1.2 per 1000 population [95% CI, 1.1-1.3]), and 1715 with dementia (0.5 per 1000 population [95% CI, 0.5-0.6]). Life expectancy for stroke survivors at age 50 was 23.4 years (95% CI, 22.3-24.5) for women and 20.7 (95% CI, 19.5-21.9) for men. CONCLUSIONS: This novel epidemiological model of stroke, poststroke CIND, and dementia draws on the best available evidence. Sensitivity analysis indicated that findings were robust to assumptions, and where there was uncertainty a conservative approach was taken. The StrokeCog model is a useful tool for service planning and cost-effectiveness analysis and is available for adaptation to other national contexts.

Non-motor features of cervical dystonia: Cognition, social cognition, psychological distress and quality of life.

INTRODUCTION: Non-motor features of cervical dystonia (CD) have been identified, including depression, anxiety, and neuropsychological deficits. The aims were: to provide a clinical neuropsychological profile of CD patients with specific focus on social cognition; assess levels of psychological distress; and investigate the relationship between non-motor features of CD, including cognitive functioning, psychological distress, CD severity, pain, and health-related quality of life (HR-QoL). METHODS: A multi-domain neuropsychological assessment battery was administered to 46 participants with CD, examining cognitive and social cognitive domains. Clinical data on dystonia severity, pain, psychological distress and HR-QoL were collected. RESULTS: The majority of participants with CD performed within the average range across most tests of cognition. Scores were significantly lower than standardized norms in social cognition, processing speed, and aspects of memory. High levels of anxiety (Hospital Anxiety and Depression Scale [HADS-A] ≥ 11, 30%) and depression (HADS-D ≥ 11; 29%) were observed. Psychological distress, CD severity, pain and HR-QoL were not significantly associated with neuropsychological functioning after controlling for multiple comparisons. Low HR-QoL was associated with higher levels of pain and psychological distress, but not severity of motor symptoms. CONCLUSION: Results indicate that psychological distress and deficits in cognitive and social cognitive functioning are likely distinct features of CD. While motor symptoms do not appear to impact HR-QoL, pain and psychological distress were associated with low HR-QoL. Findings highlight the importance of addressing non-motor symptoms in the treatment of CD.

Cognitive network hyperactivation and motor cortex decline correlate with ALS prognosis.

We aimed to quantitatively characterize progressive brain network disruption in Amyotrophic Lateral Sclerosis (ALS) during cognition using the mismatch negativity (MMN), an electrophysiological index of attention switching. We measured the MMN using 128-channel EEG longitudinally (2-5 timepoints) in 60 ALS patients and cross-sectionally in 62 healthy controls. Using dipole fitting and linearly constrained minimum variance beamforming we investigated cortical source activity changes over time. In ALS, the inferior frontal gyri (IFG) show significantly lower baseline activity compared to controls. The right IFG and both superior temporal gyri (STG) become progressively hyperactive longitudinally. By contrast, the left motor and dorsolateral prefrontal cortices are initially hyperactive, declining progressively. Baseline motor hyperactivity correlates with cognitive disinhibition, and lower baseline IFG activities correlate with motor decline rate, while left dorsolateral prefrontal activity predicted cognitive and behavioural impairment. Shorter survival correlates with reduced baseline IFG and STG activity and later STG hyperactivation. Source-resolved EEG facilitates quantitative characterization of symptom-associated and symptom-preceding motor and cognitive-behavioral cortical network decline in ALS.

Development and Psychometric Evaluation of Alternate Short Forms of the Action Naming Test.

OBJECTIVE: The action naming test (ANT) is a confrontation naming task used to assess the ability to name action words. This study aimed to create two short forms of the ANT and assess their equivalence, reliability, and comparability to the long form. METHODS: In total, 100 healthy adults (31 females and 69 males), aged 34-89 years (M = 64 and SD = 10.4) were recruited. Short forms were developed using a split-half procedure. RESULTS: No significant differences were observed between short forms on mean performance and distribution of scores for correct spontaneous responses, responses after semantic cue and total correct responses after cueing, but a higher number of accurate responses were prompted after phonemic cueing for Form A. Significant strong correlations between short forms and with the full form were encountered, although a weak correlation was found between short forms on performance after semantic cueing. IQ and age were significant predictors of action word retrieval. Whereas IQ also predicted post-cueing performance in all ANT forms, age predicted performance only for Form B. CONCLUSION: The two ANT short forms are equivalent when considering total spontaneous responses and total correct responses after cueing, but semantic and phonemic cues evoked different responses on the two forms. The two short forms were also affected differently by demographics. When the psychometric equivalence of Forms A and B was examined, the strict conditions for parallel forms were not met for all performance indices. Therefore, these newly developed short versions should be considered as alternate forms.

Cognitive reserve in amyotrophic lateral sclerosis (ALS): a population-based longitudinal study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is often associated with cognitive and/or behavioural impairment. Cognitive reserve (CR) may play a protective role in offsetting cognitive impairment. This study examined the relationship between CR and longitudinal change in cognition in an Irish ALS cohort. METHODS: Longitudinal neuropsychological assessment was carried out on 189 patients over 16 months using the Edinburgh cognitive and behavioural ALS screen (ECAS) and an additional battery of neuropsychological tests. CR was measured by combining education, occupation and physical activity data. Joint longitudinal and time-to-event models were fitted to investigate the associations between CR, performance at baseline and decline over time while controlling for non-random drop-out. RESULTS: CR was a significant predictor of baseline neuropsychological performance, with high CR patients performing better than those with medium or low CR. Better cognitive performance in high CR individuals was maintained longitudinally for ECAS, social cognition, executive functioning and confrontational naming. Patients displayed little cognitive decline over the course of the study, despite controlling for non-random drop-out. CONCLUSIONS: These findings suggest that CR plays a role in the presentation of cognitive impairment at diagnosis but is not protective against cognitive decline. However, further research is needed to examine the interaction between CR and other objective correlates of cognitive impairment in ALS.

Sustained attention to response task-related beta oscillations relate to performance and provide a functional biomarker in ALS.

Objective.To characterize the cortical oscillations associated with performance of the sustained attention to response task (SART) and their disruptions in the neurodegenerative condition amyotrophic lateral sclerosis (ALS).Approach.A randomised SART was undertaken by 24 ALS patients and 33 healthy controls during 128-channel electroencephalography (EEG). Complex Morlet wavelet transform was used to quantify non-phase-locked oscillatory activity in event-related spectral perturbations associated with performing the SART. We investigated the relationships between these perturbations and task performance, and associated motor and cognitive changes in ALS.Main results.SART induced theta-band event-related synchronization (ERS) and alpha- and beta-band event-related desynchronization (ERD), followed by rebound beta ERS, in both Go and NoGo trials across the frontoparietal axis, with NoGo trials eliciting greater theta ERS and lesser beta ERS. Controls with greater Go trial beta ERS performed with greater speed and less accuracy. ALS patients exhibited increased anticipation compared to controls but similar reaction times and accuracy. Prefrontal (area under the receiver operating characteristic curve (AUROC) = 0.8, Cohen'sd= 0.97) and parietal (AUROC = 0.82, Cohen'sd= 1.12) beta-band ERD was significantly reduced in ALS but did not relate to performance, while patients with higher Edinburgh Cognitive and Behavioural ALS Screen (ECAS) ALS-specific scores demonstrated greater ERS in beta (rho = 0.72) upon successful withholding.Significance.EEG measurement of task-related oscillation changes reveals variation in cortical network engagement in relation to speed versus accuracy strategies. Such measures can also capture cognitive and motor network pathophysiology in the absence of task performance decline, which may facilitate development of more sensitive early neurodegenerative disease biomarkers.

Extra-motor cerebral changes and manifestations in primary lateral sclerosis.

Primary lateral sclerosis (PLS) is classically considered a 'pure' upper motor neuron disorder. Motor cortex atrophy and pyramidal tract degeneration are thought to be pathognomonic of PLS, but extra-motor cerebral changes are poorly characterized. In a prospective neuroimaging study, forty PLS patients were systematically evaluated with a standardised imaging, genetic and clinical protocol. Patients were screened for ALS and HSP associated mutations, as well as C9orf72 hexanucleotide repeats. Clinical assessment included composite reflex scores, spasticity scales, functional rating scales, and screening for cognitive and behavioural deficits. The neuroimaging protocol evaluated cortical atrophy patterns, subcortical grey matter changes and white matter alterations in whole-brain and region-of-interest analyses. PLS patients tested negative for known ALS- and HSP-associated mutations and C9orf72 repeat expansions. Voxel-wise analyses revealed anterior cingulate, dorsolateral prefrontal, insular, opercular, orbitofrontal and bilateral mesial temporal grey matter changes and white matter alterations in the fornix, brainstem, temporal lobes, and cerebellum. Significant thalamus, caudate, hippocampus, putamen and accumbens nucleus volume reductions were also identified. Extra-motor clinical manifestations were dominated by verbal fluency deficits, language deficits, apathy and pseudobulbar affect. Our clinical and radiological evaluation confirms considerable extra-motor changes in a population-based cohort of PLS patients. Our data suggest that PLS should no longer be considered a neurodegenerative disorder selectively affecting the pyramidal system. PLS is associated with widespread extra-motor changes and manifestations which should be carefully considered in the multidisciplinary management of this low-incidence condition.

Blood-brain barrier permeability imaging as a predictor for delayed cerebral ischaemia following subarachnoid haemorrhage. A narrative review.

BACKGROUND: Aneurysmal subarachnoid haemorrhage is associated with significant morbidity and mortality due to the myriad of complications contributing to early brain injury and delayed cerebral ischaemia. There is increasing interest in the exploration of the association between blood-brain barrier integrity and risks of delayed cerebral ischaemia and poor outcomes. Despite recent advances in cerebral imaging, radiographic imaging of blood-brain barrier disruption, as a biomarker for outcome prediction, has not been adopted in clinical practice. METHODS: We performed a narrative review by searching for articles describing molecular changes or radiological identification of changes in BBB permeability following subarachnoid haemorrhage (SAH) on MEDLINE. Preclinical studies were analysed if reported structural changes and clinical studies were included if they investigated for radiological markers of BBB disruption and its correlation with delayed cerebral ischaemia. RESULTS: There is ample preclinical evidence to suggest that there are structural changes in BBB permeability following SAH. The available clinical literature has demonstrated correlations between permeability imaging and outcomes following aneurysmal subarachnoid haemorrhage (aSAH). CONCLUSION: Radiological biomarkers offer a potential non-invasive prognostication tool and may also allow early identifications of patients who may be at risk of DCI.

An integrated multidisciplinary model of COVID-19 recovery care.

BACKGROUND: In January 2020, the WHO declared the SARS-CoV-2 outbreak a public health emergency; by March 11, a pandemic was declared. To date in Ireland, over 3300 patients have been admitted to acute hospitals as a result of infection with COVID-19. AIMS: This article aims to describe the establishment of a COVID Recovery Service, a multidisciplinary service for comprehensive follow-up of patients with a hospital diagnosis of COVID-19 pneumonia. METHODS: A hybrid model of virtual and in-person clinics was established, supported by a multidisciplinary team consisting of respiratory, critical care, infectious diseases, psychiatry, and psychology services. This model identifies patients who need enhanced follow-up following COVID-19 pneumonia and aims to support patients with complications of COVID-19 and those who require integrated community care. RESULTS: We describe a post-COVID-19 service structure together with detailed protocols for multidisciplinary follow-up. One hundred seventy-four patients were discharged from Beaumont Hospital after COVID-19 pneumonia. Sixty-seven percent were male with a median age (IQR) of 66.5 (51-97). Twenty-two percent were admitted to the ICU for mechanical ventilation, 11% had non-invasive ventilation or high flow oxygen, and 67% did not have specialist respiratory support. Early data suggests that 48% of these patients will require medium to long-term specialist follow-up. CONCLUSIONS: We demonstrate the implementation of an integrated multidisciplinary approach to patients with COVID-19, identifying those with increased physical and mental healthcare needs. Our initial experience suggests that significant physical, psychological, and cognitive impairments may persist despite clinical resolution of the infection.

The StrokeCog study: development and description of a cognition-focused psychological intervention to address cognitive impairment following stroke.

OBJECTIVE: To describe the process of developing a cognitive rehabilitation intervention for patients with post-stroke cognitive impairment (PSCI) and to describe the intervention prior to evaluation in a pilot randomised controlled trial (RCT). Method: The Medical Research Council framework, 'Developing and evaluating complex interventions', was used to develop the cognitive rehabilitation intervention. We conducted a combined analysis of the existing evidence base for PSCI rehabilitation alongside qualitative exploration of the perspectives of stroke survivors, their families, and healthcare professionals providing stroke care, on the necessary components for a cognitive rehabilitation intervention for PSCI. The Template for Intervention Description and Replication checklist was used as a structural framework for the description of the intervention. Results: The intervention comprises a five-week intervention integrating group-based activities, supported by a clinical neuropsychologist, with home-based activities to encourage self-efficacy through the practice of adjustment and compensatory strategies learned in the group format to achieve the patients' identified goals in managing their PSCI. Conclusion: A cognitive rehabilitation intervention for patients with PSCI has been developed and described. We are in the process of developing a structured intervention manual to standardise the content and delivery of the intervention for further testing in a pilot RCT.

Omega-3 index and blood pressure responses to eating foods naturally enriched with omega-3 polyunsaturated fatty acids: a randomized controlled trial.

Diets low in seafood omega-3 polyunsaturated fatty acids (PUFAs) are very prevalent. Such diets have recently been ranked as the sixth most important dietary risk factor-1.5 million deaths and 33 million disability-adjusted life-years worldwide are attributable to this deficiency. Wild oily fish stocks are insufficient to feed the world's population, and levels of eicosapentaenoic acid and docosahexaenoic acid (DHA) in farmed fish have more than halved in the last 20 years. Here we report on a double-blinded, controlled trial, where 161 healthy normotensive adults were randomly allocated to eat at least three portions/week of omega-3-PUFA enriched (or control) chicken-meat, and to eat at least three omega-3-PUFA enriched (or control) eggs/week, for 6 months. We show that regular consumption of omega-3-PUFA enriched chicken-meat and eggs significantly increased the primary outcome, the red cell omega-3 index (mean difference [98.75% confidence interval] from the group that ate both control foods, 1.7% [0.7, 2.6]). Numbers of subjects with a very high-risk omega-3 index (index < 4%) were more than halved amongst the group that ate both enriched foods. Furthermore, eating the enriched foods resulted in clinically relevant reductions in diastolic blood pressure (- 3.1 mmHg [- 5.8, - 0.3]). We conclude that chicken-meat and eggs, naturally enriched with algae-sourced omega-3-PUFAs, may serve as alternative dietary sources of these essential micronutrients. Unlike many lifestyle interventions, long-term population health benefits do not depend on willingness of individuals to make long-lasting difficult dietary changes, but on the availability of a range of commonly eaten, relatively inexpensive, omega-3-PUFA enriched foods.

Cognitive and behavioural impairment in amyotrophic lateral sclerosis.

PURPOSE OF REVIEW: The current review provides an up to date overview of the nature and progression of the cognitive and behavioural impairment in amyotrophic lateral sclerosis (ALS). Understanding these symptoms has implications for the management of the disease and the design of clinical trials, in addition to the support of patient and caregiver regarding mental capacity and end of life decision-making. RECENT FINDINGS: Cognitive and behavioural change in ALS are best characterized as the consequence of extensive network dysfunction. 35-45% of ALS patients present with mild-moderate cognitive impairment and comorbid dementia occurs in approximately 14% of patients, the majority of these meeting diagnostic criteria for frontotemporal dementia (FTD). Cognitive change in ALS manifests most commonly as executive dysfunction and language impairment. Behavioural change in the form of apathy, disinhibition, loss of sympathy and empathy, stereotyped behaviours and dietary changes occur. SUMMARY: Cognitive and behavioural impairment is an important feature of ALS, and reflects broad network dysfunction of frontostriatal and frontotemporal systems. Cognition and behaviour should be assessed early in the diagnostic process, and data driven approaches should be developed to enable reliable quantitative outcome assessment suitable for clinical trials.

Amygdala pathology in amyotrophic lateral sclerosis and primary lateral sclerosis.

Temporal lobe studies in motor neuron disease overwhelmingly focus on white matter alterations and cortical grey matter atrophy. Reports on amygdala involvement are conflicting and the amygdala is typically evaluated as single structure despite consisting of several functionally and cytologically distinct nuclei. A prospective, single-centre, neuroimaging study was undertaken to comprehensively characterise amygdala pathology in 100 genetically-stratified ALS patients, 33 patients with PLS and 117 healthy controls. The amygdala was segmented into groups of nuclei using a Bayesian parcellation algorithm based on a probabilistic atlas and shape deformations were additionally assessed by vertex analyses. The accessory basal nucleus (p = .021) and the cortical nucleus (p = .022) showed significant volume reductions in C9orf72 negative ALS patients compared to controls. The lateral nucleus (p = .043) and the cortico-amygdaloid transition (p = .024) were preferentially affected in C9orf72 hexanucleotide carriers. A trend of total volume reduction was identified in C9orf72 positive ALS patients (p = .055) which was also captured in inferior-medial shape deformations on vertex analyses. Our findings highlight that the amygdala is affected in ALS and our study demonstrates the selective involvement of specific nuclei as opposed to global atrophy. The genotype-specific patterns of amygdala involvement identified by this study are consistent with the growing literature of extra-motor clinical features. Mesial temporal lobe pathology in ALS is not limited to hippocampal pathology but, as a key hub of the limbic system, the amygdala is also affected in ALS.