Background Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue currently approved for type 2 diabetes and obesity. Preclinical evidence in transgenic models of Alzheimer’s disease suggests that liraglutide exerts neuroprotective effects by reducing amyloid oligomers, normalising synaptic plasticity and cerebral glucose uptake, and increasing the proliferation of neuronal progenitor cells. The primary objective of the study is to evaluate the change in cerebral glucose metabolic rate after 12 months of treatment with liraglutide in participants with Alzheimer’s disease compared to those who are receiving placebo. Methods/design ELAD is a 12-month, multi-centre, randomised, double-blind, placebo-controlled, phase IIb trial of liraglutide in participants with mild Alzheimer’s dementia. A total of 206 participants will be randomised to receive either liraglutide or placebo as a daily injection for a year. The primary outcome will be the change in cerebral glucose metabolic rate in the cortical regions (hippocampus, medial temporal lobe, and posterior cingulate) from baseline to follow-up in the treatment group compared with the placebo group. The key secondary outcomes are the change from baseline to 12 months in z scores for clinical and cognitive measures (Alzheimer’s Disease Assessment Scale—Cognitive Subscale and Executive domain scores of the Neuropsychological Test Battery, Clinical Dementia Rating Sum of Boxes, and Alzheimer’s Disease Cooperative Study—Activities of Daily Living) and the incidence and severity of treatment-emergent adverse events or clinically important changes in safety assessments. Other secondary outcomes are 12-month change in magnetic resonance imaging volume, diffusion tensor imaging parameters, reduction in microglial activation in a subgroup of participants, reduction in tau formation and change in amyloid levels in a subgroup of participants measured by tau and amyloid imaging, and changes in composite scores using support machine vector analysis in the treatment group compared with the placebo group. Discussion Alzheimer’s disease is a leading cause of morbidity worldwide. As available treatments are only symptomatic, the search for disease-modifying therapies is a priority. If the ELAD trial is successful, liraglutide and GLP-1 analogues will represent an important class of compounds to be further evaluated in clinical trials for Alzheimer’s treatment. Trial registration ClinicalTrials.gov, NCT01843075 . Registration 30 April 2013. Electronic supplementary material The online version of this article (10.1186/s13063-019-3259-x) contains supplementary material, which is available to authorized users.

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson’s disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson’s disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop.Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.

Background Public health restrictions due to the COVID‐19 (SARS CoV‐2) pandemic have disproportionately affected informal caregivers of people living with long term health conditions. We aimed to explore levels of care burden, loneliness, and social isolation among caregivers of people with enduring physical and brain health conditions in English‐speaking regions worldwide, by investigating outcomes before and during the COVID‐19 pandemic. Methods A cross‐sectional anonymous online survey data from 2287 English‐speaking caregivers of people with long term health conditions from four English‐speaking regions (UK, Ireland, USA, New Zealand) included measures of care burden, loneliness, and social isolation, reported before and during the COVID‐19 pandemic. Analyses were descriptive, followed by an ordinal regression model for predictors of burden. Results Compared to pre‐pandemic levels, all caregivers experienced a significant increase in burden, loneliness, and isolation. Caregivers of people with both brain health and physical conditions were the most burdened and had the highest levels of loneliness and isolation compared to caregivers of people with either a brain health or physical condition only. The increase in care burden among caregivers of people with brain health challenges was associated with caregiver's gender, moderate and severe emotional loneliness, magnitude and frequency of isolation during the pandemic, and care circumstances (cohabitation with the care recipient, restrictions on the ability to provide care). Conclusions Health and social care interventions should target caregivers' care circumstances and psychological outcomes, particularly in women, accounting for the significant additional burden of care, loneliness, and isolation resulting from pandemic‐related restrictions.

Background Type 2 diabetes is a risk factor for Alzheimer’s disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. Methods In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. Results In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. Conclusions In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.

Background: Hearing impairment is common among older adults and affects cognitive assessments for identification of dementia which rely on good hearing function. We developed and validated a version of the Montreal Cognitive Assessment (MoCA) for people with hearing impairment.

Proposition density is differentially sensitive to aphasia type and most clearly differentiates individuals with Broca's aphasia from the other groups.

Psychiatric hospital beds for people with dementia are a limited resource. The number of people with dementia requiring inpatient psychiatric care is expected to increase as the population ages, but there is a striking lack of data informing these services. 1,2 We found almost no mention of inpatient mental health admissions in UK dementia policy or guidance. Previous literature suggests the main reasons for admission are neuropsychiatric symptoms which pose a risk of harm. 3 There is frequently a resistance to accepting care, tight legal frameworks which govern treatment and high levels of physical and psychiatric morbidity. The majority of published data is from audits of single wards or localities which means variability between units is unknown. 4,5 Our aim was to describe the clinical characteristics of patients admitted to inpatient dementia units, to establish their journey to and from the unit and describe workforce and clinical practice. | METHODSWe performed a multi-centre retrospective service evaluation, using routinely collected data from four diverse sites in the United Kingdom. Participating sites provided routinely collected service data for calendar years 2018 and 2019. This study was approved as a service evaluation. All data was anonymised at the patient level. | RESULTSResults are presented in Table 1. Three of the sites had one bed for every 200-250 people with a dementia diagnosis, though site 3 had less. Admissions averaged one per week per site. Alzheimer's disease was the most common diagnosis, followed by vascular dementia.Patients were predominantly male. Bed occupancy was high between 80% and 90%. Admissions were long with a mean duration of 100 days. There is a cohort on each ward who have longer admissions, one in six patients still remained in hospital after 6 months, and 2.5% had admissions of over 1-year duration. Most admissions were made using the Mental Health Act. Source of admission was commonly from acute hospitals or the patients' homes. Admissions levels only otherwise seen at the height of the coronavirus pandemic in the NHS. 9 Extra shifts were mostly to cover 1:1 observations, these were mostly covered through bank and agency unqualified staff, which might provide an argument for increasing staff establishment.In summary, we provide a study of nearly 500 admissions to psychiatric dementia inpatient beds and describe long lengths of stay, frequent placement in institutional care on discharge, high rates of falls and assaults and some heterogeneity of service provision. We found little previous literature on this topic and given the vulnerability and complexity of these patients suggest a larger and more detailed study to confirm these findings and inform the development of standards of optimal care.

Objectives Up to 90% of people with dementia in long term care (LTC) have hearing and/or vision impairment. Hearing/vision difficulties are frequently under‐recognised or incompletely managed. The impacts of hearing/vision impairment include more rapid cognitive decline, behavioural disturbances, reduced quality of life, and greater care burden. This research investigated LTC staff knowledge, attitudes and practice regarding hearing/vision care needs for residents with dementia. Methods A survey of staff in LTC facilities in England, South Korea, India, Greece, Indonesia and Australia. Respondents used a five‐point scale to indicate agreement or YES/NO response to questions regarding sensory‐cognitive care knowledge (what is known); attitudes (what is thought); practice (what is done). Results Respondents reported high awareness of hearing/vision care needs, although awareness of how to identify hearing/vison difficulties or refer for assessment was low. Most felt that residents were not able to use hearing/vision devices effectively due to poor fit, being poorly tolerated or lost or broken devices. A substantial minority of respondents reported low confidence in supporting use of assistive hearing/vision devices, with lack of training the main reason. Most staff did not undertake routine checking of hearing/vision devices, and it was rare for facilities to have designated staff responsible for sensory needs. Variation among countries was not significant after accounting for staff experience and having received dementia training. Conclusions There is a need to improve sensory support for people with dementia in LTC facilities internationally. Practice guidelines and training to enhance sensory‐cognitive knowledge, attitudes and practice in professional care teams is called for.