Motor cortical excitability predicts cognitive phenotypes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are well-recognised as an extended disease spectrum. This study hypothesised that cortical hyperexcitability, an early pathophysiological abnormality in ALS, would distinguish cognitive phenotypes, as a surrogate marker of pathological disease burden. 61 patients with ALS, matched for disease duration (pure motor ALS, n = 39; ALS with coexistent FTD, ALS-FTD, n = 12; ALS with cognitive/behavioural abnormalities not meeting FTD criteria, ALS-Cog, n = 10) and 30 age-matched healthy controls. Cognitive function on the Addenbrooke's cognitive examination (ACE) scale, behavioural function on the motor neuron disease behavior scale (MiND-B) and cortical excitability using transcranial magnetic stimulation (TMS) were documented. Cortical resting motor threshold (RMT), lower threshold indicating hyperexcitability, was lower in ALS-FTD (50.2 ± 6.9) compared to controls (64.3 ± 12.6, p < 0.005), while ALS-Cog (63.3 ± 12.7) and ALS (60.8 ± 13.9, not significant) were similar to controls. Short interval intracortical inhibition (SICI) was reduced across all ALS groups compared to controls, indicating hyperexcitability. On receiver operating characteristic curve analysis, RMT differentiated ALS-FTD from ALS (area under the curve AUC = 0.745, p = 0.011). The present study has identified a distinct pattern of cortical excitability across cognitive phenotypes in ALS. As such, assessment of cortical physiology may provide more precise clinical prognostication in ALS.

Eating peptides: biomarkers of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia.

Objective: Physiological changes potentially influence disease progression and survival along the Amyotrophic Lateral Sclerosis (ALS)-Frontotemporal dementia (FTD) spectrum. The peripheral peptides that regulate eating and metabolism may provide diagnostic, metabolic, and progression biomarkers. The current study aimed to examine the relationships and biomarker potential of hormonal peptides. Methods: One hundred and twenty-seven participants (36 ALS, 26 ALS- cognitive, patients with additional cognitive behavioral features, and 35 behavioral variant FTD (bvFTD) and 30 controls) underwent fasting blood analyses of leptin, ghrelin, neuropeptide Y (NPY), peptide YY (PYY), and insulin levels. Relationships between endocrine measures, cognition, eating behaviors, and body mass index (BMI) were investigated. Biomarker potential was evaluated using multinomial logistic regression for diagnosis and correlation to disease duration. Results: Compared to controls, ALS and ALS-cognitive had higher NPY levels and bvFTD had lower NPY levels, while leptin levels were increased in all patient groups. All groups had increased insulin levels and a state of insulin resistance compared to controls. Lower NPY levels correlated with increasing eating behavioral change and BMI, while leptin levels correlated with BMI. On multinomial logistic regression, NPY and leptin levels were found to differentiate between diagnosis. Reduced Neuropeptide Y levels correlated with increasing disease duration, suggesting it may be useful as a potential marker of disease progression. Interpretation: ALS-FTD is characterized by changes in NPY and leptin levels that may impact on the underlying regional neurodegeneration as they were predictive of diagnosis and disease duration, offering the potential as biomarkers and for the development of interventional treatments.

The burden of apathy for caregivers of patients with amyotrophic lateral sclerosis.

OBJECTIVES: Apathy is the most common behavioral symptom of amyotrophic lateral sclerosis (ALS). Despite its known impact on caregiver wellbeing, apathy is typically considered a unitary construct making assessment and targeting treatment problematic. The aim of this study was to explore the relationship between caregiver burden and the behavioral, cognitive, and emotional symptoms of apathy in ALS. METHODS: Fifty-one ALS patient-caregiver dyads from an ALS/frontotemporal dementia Clinic were assessed with the Apathy Evaluation Scale which measured the cognitive, behavioral, emotional, and nonspecific symptoms of apathy as well as the Zarit Burden Interview, a measure of perceived burden among caregivers of cognitively impaired older adults. The relationship between apathy and caregiver burden were analyzed using univariate and multivariate methods. RESULTS: Apathy was identified in 18% of ALS patients. Greater behavioral (p = 0.011) and nonspecific (p = 0.010) symptoms of apathy exhibited by patients were reported by caregivers with higher levels of burden compared to caregivers with lower levels of burden. Of the cognitive, behavioral, emotional, and nonspecific symptoms of apathy, only the behavioral symptoms explained a significant amount of variance in caregiver burden (p = 0.031). CONCLUSIONS: Apathy, specifically the behavioral symptoms of apathy was associated with higher burden of care among ALS caregivers, highlighting the importance of multidimensional assessment of apathy and provision of behavior management support as part of ALS care.

Primary lateral sclerosis and the amyotrophic lateral sclerosis-frontotemporal dementia spectrum.

AIM: To investigate whether primary lateral sclerosis (PLS) represents part of the amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD) spectrum of diseases. METHODS: Comprehensive assessment was taken on 21 patients with PLS and results were compared to patients diagnosed with pure motor ALS (n = 27) and ALS-FTD (n = 12). Clinical features, Addenbrooke's Cognitive Examination (ACE) scores, Motor Neuron Disease Behaviour (Mind-B) scores, motor disability on the ALS functional rating scale (ALSFRS) and survival times were documented. Motor cortex excitability was evaluated using transcranial magnetic stimulation (TMS). RESULTS: Global cognition was impaired in PLS (mean total ACE score 82.5 ± 13.6), similar to ALS-FTD (mean total ACE score 76.3 ± 7.7, p > 0.05) while behavioural impairments were not prominent. TMS revealed that resting motor threshold (RMT) was significantly higher in PLS (75.5 ± 6.2) compared ALS-FTD (50.1 ± 7.2, p < 0.001) and ALS (62.3 ± 12.6, p = 0.046). Average short-interval intracortical inhibition (SICI) was similar in all three patient groups. The mean survival time was longest in PLS (217.4 ± 22.4 months) and shortest in ALS-FTD (38.5 ± 4.5 months, p = 0.002). Bulbar onset disease (ß = - 0.45, p = 0.007) and RMT (ß = 0.54, p = 0.001) were independent predictors of global cognition while motor scores (ß = 0.47, p = 0.036) and SICI (ß = 0.58, p = 0.006) were significantly associated with ALSFRS. CONCLUSION: The cognitive profile in PLS resembles ALS-FTD, without prominent behavioural disturbances. A higher RMT in PLS than ALS and ALS-FTD is consistent with differential cortical motor neuronal abnormalities and more severe involvement of corticospinal axons while SICI, indicative of inhibitory interneuronal dysfunction was comparable with ALS and ALS-FTD. Overall, while these findings support the notion that PLS lies on the ALS-FTD spectrum, the mechanisms underlying slow disease progression are likely to be distinct in PLS.

Lipid Metabolism and Survival Across the Frontotemporal Dementia-Amyotrophic Lateral Sclerosis Spectrum: Relationships to Eating Behavior and Cognition.

BACKGROUND: Patients with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) exhibit changes in eating behavior that could potentially affect lipid levels. OBJECTIVE: This study aimed to document changes in lipid metabolism across the ALS-FTD spectrum to identify potential relationships to eating behavior (including fat intake), cognitive change, body mass index (BMI), and effect on survival. METHODS: One hundred and twenty-eight participants were recruited: 37 ALS patients, 15 ALS patients with cognitive and behavioral change (ALS-Plus), 13 ALS-FTD, 31 behavioral variant FTD, and 32 healthy controls. Fasting total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL) and triglyceride levels were measured and correlated to eating behavior (caloric, fat intake), cognitive change, and BMI; effect on survival was examined using cox regression analyses. RESULTS: There was a spectrum of lipid changes from ALS to FTD with increased triglyceride (p < 0.001), total cholesterol/HDL ratio (p < 0.001), and lower HDL levels (p = 0.001) in all patient groups compared to controls. While there was no increase in total cholesterol levels, a higher cholesterol level was found to correlate with 3.25 times improved survival (p = 0.008). Triglyceride and HDL cholesterol levels correlated to fat intake, BMI, and measures of cognition and disease duration. CONCLUSION: A spectrum of changes in lipid metabolism has been identified in ALS-FTD, with total cholesterol levels found to potentially impact on survival. These changes were mediated by changes in fat intake, and BMI, and may also be mediated by the neurodegenerative process, offering the potential to modify these factors to slow disease progression and improve survival.

A pilot study of potential brain donor satisfaction and attitudes towards telephone assessment.

OBJECTIVE: Test the feasibility of assessing cognition, psychiatric symptoms and daily living skills of potential brain donors by telephone and compare satisfaction and attitudes across telephone and face-to-face assessment. METHOD: Data were collected from 108 healthy participants from the Brains for Dementia Research cohort. Purposive sampling was used to assess feasibility and a randomised control trial design compared satisfaction and attitudes towards telephone and face-to-face assessment. Non-parametric tests were conducted to compare groups, and logistic regression was performed to assess the relationship between satisfaction and participant characteristics. RESULTS: Of the 80 participants offered telephone assessment, 67 (83.8%) agreed, 2 (2.5%) had a significant hearing impairment, 4 (5.0%) had potential memory problems and 7 (8.7%) declined. On average, telephone assessments lasted 38 min and duration was negatively associated with Telephone Interview of Cognitive Status-Modified scores (p = 0.001) and positively associated with age (p = 0.040), Neuropsychiatric Inventory scores (p = 0.019), Geriatric Depression Scale (p = 0.035) and Global Deterioration Scale (p = 0.022). Satisfaction was high in respect to organisational and personal aspects; ratings did not differ significantly across telephone and face-to-face assessment groups and were not related to socio-demographic characteristics. Participants undergoing telephone assessment were significantly more likely to hold positive attitudes towards this mode of assessment. CONCLUSIONS: Telephone assessment is feasible, time-efficient and acceptable to healthy, potential brain donors. When used with other assessment modes and within the context of established contact, telephone assessment offers greater flexibility to researchers and participants and represents an effective mechanism for overcoming the challenges of growing, ageing cohorts and uncertain resources. Copyright © 2016 John Wiley & Sons, Ltd.

Offering financial incentives to increase adherence to antipsychotic medication: the clinician experience.

Financial incentives for medication adherence in patients with psychotic disorders are controversial. It is not yet known whether fears expressed by clinicians are borne out in reality. We aimed to explore community mental health clinicians' experiences of the consequences of giving patients with psychotic disorders a financial incentive to take their depot medication. We implemented descriptive and thematic analyses of semistructured interviews with the clinicians of patients assigned to receive incentives within a randomized controlled trial. Fifty-nine clinicians were interviewed with regard to the effect of the incentives on 73 of the 78 patients allocated to receive incentives in the trial. Most commonly, the clinicians reported benefits for clinical management including improved adherence, contact, patient monitoring, communication, and trust (n = 52). Positive effects on symptoms, insight, or social functioning were reported for some (n = 33). Less commonly, problems for patient management were reported (n = 19) such as monetarization of the therapeutic relationship or negative consequences for the patient (n = 15) such as increased drug and alcohol use. Where requests for increased money occurred, they were rapidly resolved. It seems that, in most cases, the clinicians found that using incentives led to benefits for patient management and for patient health. However, in 33% of cases, some adverse effects were reported. It remains unclear whether certain clinical characteristics are associated with increased risk for adverse effects of financial incentives. The likelihood of benefit versus the smaller risk for adverse effects should be weighed up when deciding whether to offer incentives to individual patients.

Online social networking in people with psychosis: A systematic review.

BACKGROUND: Online social networking might facilitate the establishment of social contacts for people with psychosis, who are often socially isolated by the symptoms and consequences of their disorder. AIMS: We carried out a systematic review exploring available evidence on the use of online social networking in people with psychosis. METHODS: The review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies examined the use of the online social networking by people with an a priori diagnosis of psychosis (inclusive of bipolar disorder). Data from included studies were extracted and narratively synthesised. RESULTS: A total of 11 studies, published between 2005 and 2013, reported data on online social networking in people with psychosis. People with psychosis seem to spend more time in chat rooms or playing online games than control groups. The use of other online tools, such as Facebook or communication through e-mail, is lower or the same than controls. Online social networking was used by patients with psychosis for establishing new relationships, maintaining relationships/reconnecting with people and online peer support. CONCLUSION: Online social networking, in the form of forums or online chats, could play a role in strategies aimed at enhancing social networks and reduce the risk of isolation in this population.

Interventions for reducing benzodiazepine use in older people: meta-analysis of randomised controlled trials.

BACKGROUND: The use of benzodiazepines has been advised against in older people, but prevalence rates remain high. AIMS: To review the evidence for interventions aimed at reducing benzodiazepine use in older people. METHOD: We conducted a systematic review, assessment of risk of bias and meta-analyses of randomised controlled trials of benzodiazepine withdrawal and prescribing interventions. RESULTS: Ten withdrawal and eight prescribing studies met the inclusion criteria. At post-intervention, significantly higher odds of not using benzodiazepines were found with supervised withdrawal with psychotherapy (odds ratio (OR) = 5.06, 95% CI 2.68-9.57, P<0.00001) and withdrawal with prescribing interventions (OR = 1.43, 95% CI 1.02-2.02, P = 0.04) in comparison with the control interventions treatment as usual (TAU), education placebo, withdrawal with or without drug placebo, or psychotherapy alone. Significantly higher odds of not using benzodiazepines were also found for multifaceted prescribing interventions (OR = 1.37, 95% CI 1.10-1.72, P = 0.006) in comparison with control interventions (TAU and prescribing placebo). CONCLUSIONS: Supervised benzodiazepine withdrawal augmented with psychotherapy should be considered in older people, although pragmatic reasons may necessitate consideration of other strategies such as medication review.