The challenges of COVID-19 for people with dementia with Lewy bodies and family caregivers.

Introduction During the current SARS-CoV-2 pandemic dementia has been identified as disproportionally common in adults aged over 65 who develop severe COVID-19.1 Observational data from the International Severe Acute Respiratory and Emerging Infections Consortium also confirms a high prevalence of dementia in older adults hospitalised with COVID-19.2 It is so far unclear whether there is any direct effect of dementia pathologies as dementia is a disease of old age, and thus likely to be associated with a variety of comorbidities, in particular, frailty, which may further exacerbate the risk of severe infection. In addition up to one third of COVID patients have demonstrated neurological sequelae3 and there may be both direct (viral infection within the brain, vascular effects) and indirect effects (e.g. host immunological response, impact of treatment) of SARS-CoV-2 on the brain.4 It is therefore possible that SARS-CoV-2 infection may accentuate any pre-existing neurodegenerative disease

18F-FDG PET and perfusion SPECT in the diagnosis of Alzheimer and Lewy body dementias.

UNLABELLED: Brain imaging with glucose ((18)F-FDG) PET or blood flow (hexamethylpropyleneamine oxime) SPECT is widely used for the differential diagnosis of dementia, though direct comparisons to clearly establish superiority of one method have not been undertaken. METHODS: Subjects with Alzheimer disease (AD; n = 38) and dementia with Lewy bodies (DLB; n = 30) and controls (n = 30) underwent (18)F-FDG PET and SPECT in balanced order. The main outcome measure was area under the curve (AUC) of receiver-operating-characteristic analysis of visual scan rating. RESULTS: Consensus diagnosis with (18)F-FDG PET was superior to SPECT for both dementia vs. no-dementia (AUC = 0.93 vs. 0.72, P = 0.001) and AD vs. DLB (AUC = 0.80 vs. 0.58, P = 0.005) comparisons. The sensitivity and specificity for dementia/no-dementia was 85% and 90%, respectively, for (18)F-FDG PET and 71% and 70%, respectively, for SPECT. CONCLUSION: (18)F-FDG PET was significantly superior to blood flow SPECT. We recommend (18)F-FDG PET be performed instead of perfusion SPECT for the differential diagnosis of degenerative dementia if functional imaging is indicated.We thank the Dementia and Neurodegenerative Diseases Research Network (DeNDRoN) for valuable support with clinical recruitment. We also thank the National Institute for Health Research.This research was originally published in JNM. O’Brien JT, Firbank MJ, Davison C, Barnett N, Bamford C, Donaldson C, Olsen K, Herholz K, Williams D, Lloyd J. 18F-FDG PET and Perfusion SPECT in the Diagnosis of Alzheimer and Lewy Body Dementias. JNM. 2014;55:1959–1965. © by the Society of Nuclear Medicine and Molecular Imaging, Inc

Peripheral inflammation in prodromal Alzheimer's and Lewy body dementias.

OBJECTIVES: There is growing evidence for the role of systemic inflammation in Alzheimer's disease (AD) and other neurodegenerative diseases; however the systemic inflammatory profile in dementia with Lewy bodies (DLB) has never before been investigated. This study aimed to characterise systemic inflammatory mediators in established DLB and AD, as well as in their prodromal, mild cognitive impairment (MCI) phases. METHODS: We obtained plasma samples from patients with DLB (n=37), AD (n=20), MCI with DLB profile (n=38), MCI with AD profile (n=20) and healthy control subjects (n=20). The following inflammatory biomarkers were measured using Roche cobas c702 and Meso Scale Discovery V-Plex Plus: high-sensitivity C-reactive protein, interferon-gamma, interleukin (IL)-10, IL-12p70, IL-13, IL-1beta, IL-2, IL-4, IL-6, IL-8 and tumour necrosis factor-alpha. RESULTS: We found significantly higher levels of IL-10, IL-1beta, IL-4 and IL-2 in both MCI groups (P<0.001), while there was no significant difference in inflammatory markers between dementia groups and controls. Furthermore, increased disease severity was associated with lower levels of IL-1beta, IL-2 and IL-4 (P<0.05). INTERPRETATION: We have shown for the first time that in both DLB and AD, increased peripheral inflammation occurs early at the MCI disease stages. These data support a role for inflammation early in the disease process, and have important implications for the stage of disease where trials of anti-inflammatory medication should be focused.We would like to acknowledge our funders; the National Institute for Health Research (NIHR) Newcastle Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne NHS Foundation Trust and Newcastle University. Thanks to The Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Eleanor King is also grateful to the Royal College of Psychiatrists Pathfinder Fellowship for the grant that was provided for this project. We would also like to thank Melanie Maitland and friends for their donations to our research in Lewy Body Dementi

Exploring Public Perceptions and Understanding of Dementia: Analysing Narratives from the Mass Observation Project

Over 850,000 people living in the United Kingdom have been diagnosed with dementia, yet knowledge about this condition amongst the general population remains relatively poor. Many studies have evaluated the level of public knowledge and understanding about dementia from a research and professional service perspective, however none have considered this condition from the perspective of the wider public. In this preliminary overview, we analyse and describe high level narratives collected from 143 respondents to a dementia Directive commissioned to the Mass Observation Project. These narratives present a perspective on the public knowledge and understanding about dementia not previously considered, where respondents have written openly about their own experiences, and reflected on their perception of the wider public’s knowledge and understanding about dementia. This unique perspective importantly enhances our knowledge about the public’s understanding and awareness of dementia, and informs the main areas of public concern found in the analysis: care responsibilities, impact on relationships, and fears about developing dementia

Transcranial direct current stimulation in the treatment of visual hallucinations in Charles Bonnet syndrome: A randomized placebo-controlled crossover trial.

Objective To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet Syndrome (CBS). Design Randomized, double-masked(blind), placebo-controlled crossover trial. Participants Sixteen individuals diagnosed with CBS secondary to visual impairment caused by eye disease experiencing recurrent visual hallucinations. Intervention All participants received four consecutive days of active and placebo cathodal stimulation (current density: 0.29mA/cm2) to the visual cortex (Oz) over two defined treatment weeks, separated by a four-week wash-out period. Main Outcome Measures Ratings of visual hallucination frequency and duration following active and placebo stimulation, accounting for treatment order, using a 2x2 repeated measures model. Secondary outcomes included impact ratings of visual hallucinations and electrophysiological measures. Results When compared to placebo treatment, active inhibitory stimulation of visual cortex resulted in a significant reduction in the frequency of visual hallucinations measured by the North East Visual Hallucinations Interview, with a moderate-to-large effect size. Impact measures of visual hallucinations improved in both placebo and active conditions suggesting support and education for CBS may have therapeutic benefits. Participants who demonstrated greater occipital excitability on electroencephalography assessment at the start of treatment were more likely to report a positive treatment response. Stimulation was found to be tolerable in all participants with no significant adverse effects reported, including no deterioration in pre-existing visual impairment. Conclusions Findings indicate that inhibitory tDCS of visual cortex may reduce the frequency of visual hallucinations in people with CBS, particularly individuals who demonstrate greater occipital excitability prior to stimulation. tDCS may offer a feasible, novel intervention option for CBS with no significant side effects, warranting larger scale clinical trials to further characterize its efficacy

Microbleeds in dementia with Lewy bodies

Funder: Avid Radiopharmaceuticals; doi: http://dx.doi.org/10.13039/100014392Abstract: Introduction: Microbleeds are associated with the development of dementia in older people and are common in Alzheimer’s disease (AD). Their prevalence and clinical importance in dementia with Lewy bodies (DLB) is unclear. The objective of this study was to compare the rates of microbleeds in DLB with those in AD and healthy older people, and investigate associations between microbleeds and amyloid deposition, vascular risk and disease severity in DLB. Methods: DLB (n = 30), AD (n = 18) and control (n = 20) participants underwent clinical assessment at baseline and 1 year in this longitudinal observational study. 3T MRI (including T2* susceptibility weighted imaging) and florbetapir PET were carried out at baseline. Microbleeds were rated visually and a standardised uptake value ratio (SUVR) was calculated from florbetapir PET scans. Results: 40% of DLB subjects had microbleeds compared with 50% of AD and 15% of controls. Compared to DLB without microbleeds, those with microbleeds had higher systolic BP (156 ± 26 v. 135 ± 19 mmHg; p = 0.03), but did not have greater levels of vascular disease or amyloid deposition (SUVR 1.25 ± 0.24 v. 1.25 ± 0.22; p = 0.33). There was evidence of less severe dementia in DLB participants with microbleeds, but these differences may have been driven by a shorter disease duration in those with microbleeds. Conclusion: The presence of microbleeds in DLB is associated with higher blood pressure, but not with other measures of vascular disease or amyloid deposition. The relationship between microbleeds and clinical presentation remains unclear

Accuracy of dopaminergic imaging as a biomarker for mild cognitive impairment with Lewy bodies.

BACKGROUND: Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain. AIMS: To provide robust prospective evidence of the diagnostic accuracy of dopaminergic imaging at the MCI stage to either support or refute its inclusion as a biomarker for the diagnosis of MCI with Lewy bodies. METHOD: We conducted a prospective diagnostic accuracy study of baseline dopaminergic imaging with [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane single-photon emission computerised tomography (123I-FP-CIT SPECT) in 144 patients with MCI. Images were rated as normal or abnormal by a panel of experts with access to striatal binding ratio results. Follow-up consensus diagnosis based on the presence of core features of Lewy body disease was used as the reference standard. RESULTS: At latest assessment (mean 2 years) 61 patients had probable MCI with Lewy bodies, 26 possible MCI with Lewy bodies and 57 MCI due to Alzheimer's disease. The sensitivity of baseline FP-CIT visual rating for probable MCI with Lewy bodies was 66% (95% CI 52-77%), specificity 88% (76-95%) and accuracy 76% (68-84%), with positive likelihood ratio 5.3. CONCLUSIONS: It is over five times as likely for an abnormal scan to be found in probable MCI with Lewy bodies than MCI due to Alzheimer's disease. Dopaminergic imaging appears to be useful at the MCI stage in cases where Lewy body disease is suspected clinically