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Impaired olfaction may be a biomarker for early Lewy body disease, but its value in mild cognitive impairment with Lewy bodies (MCI-LB) is unknown. We compared olfaction in MCI-LB with MCI due to Alzheimer’s disease (MCI-AD) and healthy older adults. We hypothesized that olfactory function would be worse in probable MCI-LB than in both MCI-AD and healthy comparison subjects (HC).
Cross-sectional study assessing olfaction using Sniffin’ Sticks 16 (SS-16) in MCI-LB, MCI-AD, and HC with longitudinal follow-up. Differences were adjusted for age, and receiver operating characteristic (ROC) curves were used for discriminating MCI-LB from MCI-AD and HC.
Participants were recruited from Memory Services in the North East of England.
Thirty-eight probable MCI-LB, 33 MCI-AD, 19 possible MCI-LB, and 32HC.
Olfaction was assessed using SS-16 and a questionnaire.
Participants with probable MCI-LB had worse olfaction than both MCI-AD (age-adjusted mean difference (B) = 2.05, 95% CI: 0.62–3.49, p = 0.005) and HC (B = 3.96, 95% CI: 2.51–5.40, p < 0.001). The previously identified cutoff score for the SS-16 of ≤ 10 had 84% sensitivity for probable MCI-LB (95% CI: 69–94%), but 30% specificity versus MCI-AD. ROC analysis found a lower cutoff of ≤ 7 was better (63% sensitivity for MCI-LB, with 73% specificity vs MCI-AD and 97% vs HC). Asking about olfactory impairments was not useful in identifying them.
MCI-LB had worse olfaction than MCI-AD and normal aging. A lower cutoff score of ≤ 7 is required when using SS-16 in such patients. Olfactory testing may have value in identifying early LB disease in memory services.
The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed).
Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer’s disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer’s Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall.
MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p = .03, g = .45; Digit Symbol Substitution Test (DSST): p = .04, g = .47; DSST Error Check: p < .001, g = .68] and executive function [Trail Making Test Ratio (A/B): p = .04, g = .52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p = .01, g = .46) and verbal (Rey Auditory Verbal Learning Test: p = .04, g = .42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps > .05)
MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.
Electroencephalographic (EEG) abnormalities are greater in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) than in MCI due to Alzheimer’s disease (MCI-AD) and may anticipate the onset of dementia. We aimed to assess whether quantitative EEG (qEEG) slowing would predict a higher annual hazard of dementia in MCI across these etiologies. MCI patients (n = 92) and healthy comparators (n = 31) provided qEEG recording and underwent longitudinal clinical and cognitive follow-up. Associations between qEEG slowing, measured by increased theta/alpha ratio, and clinical progression from MCI to dementia were estimated with a multistate transition model to account for death as a competing risk, while controlling for age, cognitive function, and etiology classified by an expert consensus panel.
Over a mean follow-up of 1.5 years (SD = 0.5), 14 cases of incident dementia and 5 deaths were observed. Increased theta/alpha ratio on qEEG was associated with increased annual hazard of dementia (hazard ratio = 1.84, 95% CI: 1.01–3.35). This extends previous findings that MCI-LB features early functional changes, showing that qEEG slowing may anticipate the onset of dementia in prospectively identified MCI.
Initially proposed a little over twenty years ago, the history and practice of the Twin Peaks model falls into three discrete periods or episodes. This chapter explores each of these episodes, tracing the evolution of the model from an academic concept, which was criticised by many regulators and market practitioners for its impracticality, to its post-Global Financial Crisis rehabilitation as an institutional arrangement that is capable of addressing some of the most obvious shortcomings in regulatory structures revealed by the crisis. This chapter provides a brief overview of each of these episodes, with the focus on the first of them (that is, the rationale and background to the Twin Peaks concept and its consideration in the United Kingdom during the mid-1990s). The rationale and background to the Twin Peaks concept is explained, along with the factors that contributed to the debate on regulatory structure in the United Kingdom in the mid-1990s. The subsequent episodes are more extensively covered in other contributions to this volume and therefore their coverage in this chapter is correspondingly schematic.
Digital vaccination certification involves making many promises, few of which can realistically be kept. In this paper, we demonstrate how this phenomenon constitutes various forms of theatre – immunity theatre, border theatre, behavioural theatre and equality theatre – doing so by drawing on perspectives from technology regulation, migration studies and critical geopolitics. Technological theatre and political theatre often serve valid functions, but these forms are problematic for several reasons. First, they involve real-world infrastructures that, while unlikely to accomplish the task at hand, will nevertheless last a long time and be repurposed. They therefore constitute governance by data infrastructure, diverting action and control away from elected legislators to for-profit contractors. Second, vaccine certification effectively legitimises inequalities between countries and people by formalising ways to distinguish between the vaccinated and non-vaccinated and to exclude the latter, thus reinforcing both mobility and connectivity divides. It serves as a way to (further) close borders and to regulate, through code and infrastructure, access to public goods such as employment and public space. Finally, the project of certification displaces a more important action, namely addressing the radical inequality in countries’ ability to combat the pandemic.
Lichens are a well-known symbiosis between a host mycobiont and eukaryote algal or cyanobacterial photobiont partner(s). Recent studies have indicated that terrestrial lichens can also contain other cryptic photobionts that increase the lichens’ ecological fitness in response to varying environmental conditions. Marine lichens live in distinct ecosystems compared with their terrestrial counterparts because of regular submersion in seawater and are much less studied. We performed bacteria 16S and eukaryote 18S rRNA gene metabarcoding surveys to assess total photobiont diversity within the marine lichen Lichina pygmaea (Lightf.) C. Agardh, which is widespread throughout the intertidal zone of Atlantic coastlines. We found that in addition to the established cyanobacterial photobiont Rivularia, L. pygmaea is also apparently host to a range of other marine and freshwater cyanobacteria, as well as marine eukaryote algae in the family Ulvophyceae (Chlorophyta). We propose that symbiosis with multiple freshwater and marine cyanobacteria and eukaryote photobionts may contribute to the ability of L. pygmaea to survive the harsh fluctuating environmental conditions of the intertidal zone.
Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.
Food security status is a continuum ranging from high to very low food security. While marginal food security falls next to high food security on the spectrum, new quantitative research indicates marginal food security status is associated with negative health outcomes and poor academic performance among college students. Qualitative research focusing on college students experiencing marginal food security has not been conducted. The current study aims to qualitatively explore experiences of college students with marginal food security and to identify themes to better understand and provide context regarding how marginal food security impacts students.
Students were recruited for semi-structured interviews with questions designed to study the challenges associated with students’ food situations. All interviews were recorded and transcribed with themes identified via an inductive approach.
A large public university on the US west coast.
Thirty college students.
Key themes that emerged: purchasing cheap unhealthy foods, insufficient time to prepare and eat meals on a regular basis, stress and anxiety around the inability to eat healthy food and future health issues, self-perception of health when eating poorly along with physical symptoms and low academic motivation by not fully participating in their courses due to few healthy food options or missing meals.
Marginal food security can potentially diminish students’ health and their capacity to learn and succeed in their coursework. The results emphasise that students experiencing marginal food security should not be grouped with students experiencing high food security.
Iron overload states can be classified as primary or secondary. There are many disorders that can lead to iron overload (Table 29.1) [1, 2]. This chapter focuses on hereditary hemochromatosis (HH), juvenile hemochromatosis (JHH), and secondary iron overload (primarily transfusion associated) in the pediatric patient and in neonatal hemochromatosis (NH).
A young adult with late diagnosis of scimitar syndrome underwent infradiaphragmatic baffling of the scimitar vein to left atrium through an intra-atrial tunnel using PhotoFix® bovine pericardium with recurrent extensive fibrovascular granulation of the patch causing pulmonary and systemic venous obstruction leading to eventual explantation of the bovine pericardium.
Social anxiety disorder (SAD) is common. It usually starts in adolescence, and without treatment can disrupt key developmental milestones. Existing generic treatments are less effective for young people with SAD than with other anxiety disorders, but an adaptation of an effective adult therapy (CT-SAD-A) has shown promising results for adolescents.
The aim of this study was to conduct a qualitative exploration to contribute towards the evaluation of CT-SAD-A for adoption into Child and Adolescent Mental Health Services (CAMHS).
We used interpretative phenomenological analysis (IPA) to analyse the transcripts of interviews with a sample of six young people, six parents and seven clinicians who were learning the treatment.
Three cross-cutting themes were identified: (i) endorsing the treatment; (ii) finding therapy to be collaborative and active; challenging but helpful; and (iii) navigating change in a complex setting. Young people and parents found the treatment to be useful and acceptable, although simultaneously challenging. This was echoed by the clinicians, with particular reference to integrating CT-SAD-A within community CAMHS settings.
The acceptability of the treatment with young people, their parents and clinicians suggests further work is warranted in order to support its development and implementation within CAMHS settings.
Haematopoietic stem cell transplantation is an important and effective treatment strategy for many malignancies, marrow failure syndromes, and immunodeficiencies in children, adolescents, and young adults. Despite advances in supportive care, patients undergoing transplant are at increased risk to develop cardiovascular co-morbidities.
This study was performed as a feasibility study of a rapid cardiac MRI protocol to substitute for echocardiography in the assessment of left ventricular size and function, pericardial effusion, and right ventricular hypertension.
A total of 13 patients were enrolled for the study (age 17.5 ± 7.7 years, 77% male, 77% white). Mean study time was 13.2 ± 5.6 minutes for MRI and 18.8 ± 5.7 minutes for echocardiogram (p = 0.064). Correlation between left ventricular ejection fraction by MRI and echocardiogram was good (ICC 0.76; 95% CI 0.47, 0.92). None of the patients had documented right ventricular hypertension. Patients were given a survey regarding their experiences, with the majority both perceiving that the echocardiogram took longer (7/13) and indicating they would prefer the MRI if given a choice (10/13).
A rapid cardiac MRI protocol was shown feasible to substitute for echocardiogram in the assessment of key factors prior to or in follow-up after haematopoietic stem cell transplantation.
The literature on nineteenth-century Newcastle city region is a narrative of industrial progress premised upon technological prowess. But there is another story to be told about the transformation of a relatively small northern town into a conurbation with the attributes of a modern city. This second process of ‘rounding out’ the city with social, cultural and political institutions to accompany the economic prowess is relatively under-reported. In this study, we follow 1,621 individuals and compare their record of being mentioned in the literature to their participation in 343 local institutions. The focus is directed towards those who are much more visible in the literature compared to institutional membership – ‘narrative heroes’ – and those with the reverse pattern, much more to be found in institutions than in the literature – civic builders. The two sets of individuals are discussed and reasons for their contrasting positions are suggested.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
Cholinergic deficits are a hallmark of Alzheimer’s disease (AD) and Lewy body dementia (LBD). The nucleus basalis of Meynert (NBM) provides the major source of cortical cholinergic input; studying its functional connectivity might, therefore, provide a tool for probing the cholinergic system and its degeneration in neurodegenerative diseases. Forty-six LBD patients, 29 AD patients, and 31 healthy age-matched controls underwent resting-state functional magnetic resonance imaging (fMRI). A seed-based analysis was applied with seeds in the left and right NBM to assess functional connectivity between the NBM and the rest of the brain. We found a shift from anticorrelation in controls to positive correlations in LBD between the right/left NBM and clusters in right/left occipital cortex. Our results indicate that there is an imbalance in functional connectivity between the NBM and primary visual areas in LBD, which provides new insights into alterations within a part of the corticopetal cholinergic system that go beyond structural changes.
Dopaminergic imaging is an established biomarker for dementia with Lewy bodies, but its diagnostic accuracy at the mild cognitive impairment (MCI) stage remains uncertain.
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.
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.
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.
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.
Type 2 diabetes results mainly from weight gain in adult life and affects one in twelve people worldwide. In the Diabetes REmission Clinical Trial (DiRECT), the primary care-led Counterweight-Plus weight management program achieved remission of type 2 diabetes (for up to six years) for forty-six percent of patients after one year and thirty-six percent after two years. The objective of this study was to estimate the implementation costs of the program, as well as its two-year within-trial cost effectiveness and lifetime cost effectiveness.
Within-trial cost effectiveness included the Counterweight-Plus costs (including training, practitioner appointments, and low-energy diet), medications, and all routine healthcare contacts, combined with achieved remission rates. Lifetime cost per quality-adjusted life-year (QALY) was estimated according to projected durations of remissions, assuming continued relapse rates as seen in year two of DiRECT and the consequent life expectancy, quality of life and healthcare costs.
The two-year intervention cost was EUR 1,580 per participant, with over eighty percent of the costs incurred in year one. Compared with the control group, medication savings were EUR 259 (95% confidence interval [CI]: 166–352) for anti-diabetes drugs and EUR 29 (95% CI: 12–47) for anti-hypertensive medications. The intervention was modeled with a lifetime horizon to achieve a mean 0.06 (95% CI: 0.04–0.09) gain in QALYs for the DiRECT population and a mean total lifetime cost saving per participant of EUR 1,497 (95% CI: 755–2,331), with the intervention becoming cost-saving within six years.
The intensive weight loss and maintenance program reduced the cost of anti-diabetes drugs through improved metabolic control, achieved diabetes remission in over one-third of participants, and reduced total healthcare contacts and costs over two years. A substantial lifetime healthcare cost saving is anticipated from periods of diabetes remission and delaying complications. Healthcare resources could be shifted cost effectively to establish diabetes remission services, using the existing DiRECT intervention, even if remissions are only maintained for limited durations. However, more research investment is needed to further improve weight-loss maintenance and extend remissions.