Facilitators and barriers to adaptive implementation of the Meeting Centers Support Program (MCSP) in three European countries; the process evaluation within the MEETINGDEM study.

Unlabelled: ABSTRACTBackground:In the MEETINGDEM project, the Meeting Centers Support Program (MCSP) was adaptively implemented and evaluated in three European countries: Italy, Poland, and the United Kingdom. The aim of this study was to investigate overall and country-specific facilitators and barriers to the implementation of MCSP in these European countries.

Methods: A qualitative multiple case study design was used.

Clinic variation in glycaemic control for children with Type 1 diabetes in England and Wales: a population-based, multilevel analysis.

Aim: To understand the scope for improving children's glycaemic outcomes by reducing variation between clinics and examine the role of insulin regimen and clinic characteristics.

Methods: Cross-sectional analysis of 2012-2013 National Paediatric Diabetes Audit data from 21 773 children aged < 19 years with Type 1 diabetes cared for at 176 clinics organized into 11 regional diabetes networks in England and Wales. Variation in HbA was explored by multilevel models with a random effect for clinic.

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data.

Major depressive disorder (MDD) and Alzheimer's disease (AD) are both common in older age and frequently co-occur. Numerous phenotypic studies based on clinical diagnoses suggest that a history of depression increases risk of subsequent AD, although the basis of this relationship is uncertain. Both illnesses are polygenic, and shared genetic risk factors could explain some of the observed association.

Distinct subtypes of Alzheimer's disease based on patterns of brain atrophy: longitudinal trajectories and clinical applications.

Atrophy patterns on MRI can reliably predict three neuropathological subtypes of Alzheimer's disease (AD): typical, limbic-predominant, or hippocampal-sparing. A method to enable their investigation in the clinical routine is still lacking. We aimed to (1) validate the combined use of visual rating scales for identification of AD subtypes; (2) characterise these subtypes at baseline and over two years; and (3) investigate how atrophy patterns and non-memory cognitive domains contribute to memory impairment.

Big data and data repurposing - using existing data to answer new questions in vascular dementia research.

Introduction: Traditional approaches to clinical research have, as yet, failed to provide effective treatments for vascular dementia (VaD). Novel approaches to collation and synthesis of data may allow for time and cost efficient hypothesis generating and testing. These approaches may have particular utility in helping us understand and treat a complex condition such as VaD.

Clinical practice with anti-dementia drugs: A revised (third) consensus statement from the British Association for Psychopharmacology.

The British Association for Psychopharmacology coordinated a meeting of experts to review and revise its previous 2011 guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A-D, with A having the strongest evidence base (from randomised controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and both structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography and single photon emission computerised tomography) brain imaging can improve diagnostic accuracy in particular situations (B).

Typical and atypical appearance of early-onset Alzheimer's disease: A clinical, neuroimaging and neuropathological study.

The International Working Group (IWG) has classified Alzheimer's disease (AD) as two different types, the typical form and the atypical form, but clinicopathological studies of atypical AD are limited. Because atypical AD cases usually present with early-onset dementia, we investigated 12 patients with early-onset AD, including two patients with typical AD and 10 patients with atypical AD. Of these patients, six had the posterior variant, three had the frontal variant and one had the logopenic variant mixed with semantic dementia.

The Mild Behavioral Impairment Checklist (MBI-C): A Rating Scale for Neuropsychiatric Symptoms in Pre-Dementia Populations.

Background: Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer's Research and Treatment - Alzheimer's Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as described.

Not re-inventing the wheel: the adaptive implementation of the meeting centres support programme in four European countries.

Objectives: The implementation of new health services is a complex process. This study investigated the first phase of the adaptive implementation of the Dutch Meeting Centres Support Programme (MCSP) for people with dementia and their carers in three European countries (Italy, Poland, the UK) within the JPND-MEETINGDEM project. Anticipated and experienced factors influencing the implementation, and the efficacy of the implementation process, were investigated.

Genetic Risk as a Marker of Amyloid-β and Tau Burden in Cerebrospinal Fluid.

Background: The search for a biomarker of Alzheimer's disease (AD) pathology (amyloid-β (Aβ) and tau) is ongoing, with the best markers currently being measurements of Aβ and tau in cerebrospinal fluid (CSF) and via positron emission tomography (PET) scanning. These methods are relatively invasive, costly, and often have high screening failure rates. Consequently, research is aiming to elucidate blood biomarkers of Aβ and tau.

Environmental risk factors for dementia: a systematic review.

Background: Dementia risk reduction is a major and growing public health priority. While certain modifiable risk factors for dementia have been identified, there remains a substantial proportion of unexplained risk. There is evidence that environmental risk factors may explain some of this risk.

How do we enhance undergraduate healthcare education in dementia? A review of the role of innovative approaches and development of the Time for Dementia Programme.

Objectives: Traditional healthcare education, delivered through a series of time-limited clinical placements, often fails to deliver an understanding of the experiences of those with long-term conditions, a growing issue for healthcare systems. Responses include longitudinal integrated clerkships and senior mentor programmes allowing students' longer placements, continuity of contact and opportunities to learn about chronic illness and patient experience. We review their development and delivery in dementia and present the Time for Dementia (TFD) Programme, a novel 2-year interdisciplinary educational programme.

Cognitive function and activities of daily living in people affected by leprosy: A cross-sectional, population-based, case-control study.

Objectives: There has been controversy regarding whether or not people affected by leprosy have more cognitive dysfunction than healthy individuals. The purpose of this study was to assess cognitive functions and activities of daily living (ADL) in people affected by leprosy relative to a control population living in rural areas.

Materials And Methods: We assessed cognitive functions and ADL using the Korean Mini-Mental State Examination (K-MMSE), Korean Dementia Screening Questionnaire (KDSQ), and Seoul-Instrumental ADL (S-IADL).

White matter hyperintensities are a core feature of Alzheimer's disease: Evidence from the dominantly inherited Alzheimer network.

Objective: White matter hyperintensities (WMHs) are areas of increased signal on T2-weighted magnetic resonance imaging (MRI) scans that most commonly reflect small vessel cerebrovascular disease. Increased WMH volume is associated with risk and progression of Alzheimer's disease (AD). These observations are typically interpreted as evidence that vascular abnormalities play an additive, independent role contributing to symptom presentation, but not core features of AD.

Identification of Adverse Drug Events from Free Text Electronic Patient Records and Information in a Large Mental Health Case Register.

Objectives: Electronic healthcare records (EHRs) are a rich source of information, with huge potential for secondary research use. The aim of this study was to develop an application to identify instances of Adverse Drug Events (ADEs) from free text psychiatric EHRs.

Methods: We used the GATE Natural Language Processing (NLP) software to mine instances of ADEs from free text content within the Clinical Record Interactive Search (CRIS) system, a de-identified psychiatric case register developed at the South London and Maudsley NHS Foundation Trust, UK.

'There's a letter called ef' on Challenges and Repair in Interpreter-Mediated Tests of Cognitive Functioning in Dementia Evaluations: A Case Study.

In the Scandinavian countries Sweden, Denmark, Norway, and Finland, the number of first generation migrants reaching an old age, who will be in need of age-related health-care, is rapidly increasing. This situation poses new demands on health-care facilities, such as memory clinics, where patients with memory problems and other dementia symptoms are referred for examination and evaluation. Very many elderly people with a foreign background require the assistance of an interpreter in their encounter with health-care facilities.

Polygenic Overlap Between C-Reactive Protein, Plasma Lipids, and Alzheimer Disease.

Background: Epidemiological findings suggest a relationship between Alzheimer disease (AD), inflammation, and dyslipidemia, although the nature of this relationship is not well understood. We investigated whether this phenotypic association arises from a shared genetic basis.

Methods And Results: Using summary statistics (P values and odds ratios) from genome-wide association studies of >200 000 individuals, we investigated overlap in single-nucleotide polymorphisms associated with clinically diagnosed AD and C-reactive protein (CRP), triglycerides, and high- and low-density lipoprotein levels.

Amyloid-beta (1-40) and the risk of death from cardiovascular causes in patients with coronary heart disease.

Background: The amyloid beta peptide is the major protein constituent of neuritic plaques in Alzheimer disease and appears to play a central role in vascular inflammation pathophysiology.

Objectives: This study sought to determine the clinical value of amyloid-beta 1-40 (Abeta40) measurement in predicting cardiovascular (CV) mortality in patients with coronary heart disease (CHD) and arterial stiffness progression in young healthy subjects.

Methods: Abeta40 was retrospectively measured in blood samples collected from 3 independent prospective cohorts and 2 case-control cohorts (total N = 1,464).

Diffusion tensor imaging of Parkinson's disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study.

Although often clinically indistinguishable in the early stages, Parkinson's disease (PD), Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP) have distinct neuropathological changes. The aim of the current study was to identify white matter tract neurodegeneration characteristic of each of the three syndromes. Tract-based spatial statistics (TBSS) was used to perform a whole-brain automated analysis of diffusion tensor imaging (DTI) data to compare differences in fractional anisotropy (FA) and mean diffusivity (MD) between the three clinical groups and healthy control subjects.

Increased cerebrospinal fluid calpain activity and microparticle levels in Alzheimer's disease.

Background: Calpain has been associated with the pathophysiology of Alzheimer's disease (AD) and with apoptotic neuronal cell death leading to microparticles (MPs) formation.

Methods: A total of 64 patients with AD and 52 age- and gender-matched cognitively healthy elderly controls were included in the study. We measured calpain activity and levels of MPs, amyloid beta (Aβ1-42), h-tau, and p-tau181.

TheHiveDB image data management and analysis framework.

The hive database system (theHiveDB) is a web-based brain imaging database, collaboration, and activity system which has been designed as an imaging workflow management system capable of handling cross-sectional and longitudinal multi-center studies. It can be used to organize and integrate existing data from heterogeneous projects as well as data from ongoing studies. It has been conceived to guide and assist the researcher throughout the entire research process, integrating all relevant types of data across modalities (e.

Use and safety of antipsychotics in behavioral disorders in elderly people with dementia.

In recent years, the use of antipsychotics has been widely debated for reasons concerning their safety in elderly patients affected with dementia. To update the use of antipsychotics in elderly demented people, a MEDLINE search was conducted using the following terms: elderly, conventional and atypical antipsychotics, adverse events, dementia, and behavioral and psychotic symptoms in dementia (BPSD). Owing to the large amounts of studies on antipsychotics, we mostly restricted the field of research to the last 10 years.

Candidate blood proteome markers of Alzheimer's disease onset and progression: a systematic review and replication study.

A blood-based protein biomarker, or set of protein biomarkers, that could predict onset and progression of Alzheimer's disease (AD) would have great utility; potentially clinically, but also for clinical trials and especially in the selection of subjects for preventative trials. We reviewed a comprehensive list of 21 published discovery or panel-based (> 100 proteins) blood proteomics studies of AD, which had identified a total of 163 candidate biomarkers. Few putative blood-based protein biomarkers replicate in independent studies but we found that some proteins do appear in multiple studies; for example, four candidate biomarkers are found to associate with AD-related phenotypes in five independent research cohorts in these 21 studies: α-1-antitrypsin, α-2-macroglobulin, apolipoprotein E, and complement C3.

[Strategy and perspectives for development of Alzheimer disease-modifying drugs].

Although there has been a much progress in the clarification of the pathophysiology of Alzheimer disease (AD) over the last two decades, bona fide drugs that suppress the emergence and progression of the disease are not available yet. Fortunately, in addition to donepezil, two other cholinesterase inhibitors, namely galantamine and rivastigmine, and an NMDA receptor antagonist, memantine, have recently been approved for the treatment of AD patients at mild to moderately severe and moderately severe to severe stages of the disease, respectively, in Japan. These drugs potentially improve symptoms of AD; however, their disease-modifying effects are limited.