Minor and subthreshold depressive disorders in Alzheimer's disease: a systematic review and meta-analysis of prevalence studies

Background: Depressive symptoms are common in Alzheimer's disease (AD) and negatively impact patient well-being. The main aim of the present study was to establish summary estimates for the prevalence of minor depressive disorder (MinD) and subthreshold depression in AD and synthesise evidence on prognosis and management of these symptoms in order to inform clinical guidelines. / Methods: Systematic review and meta-analysis of cross-sectional and longitudinal studies of prevalence, prognosis, and treatments for minor and subthreshold depression in AD. We searched MEDLINE, Embase, PsycINFO and CINAHL. We included studies that reported prevalence of subthreshold depressive disorders and those reporting data on validity of diagnostic criteria, mechanisms, or randomised controlled clinical trials (RCTs) testing effectiveness of interventions. Estimates of prevalence were pooled using random-effects meta-analyses. Two authors screened articles and independently extracted data on study characteristics. / Results: We reviewed 5671 abstracts, retrieved 621 full text articles and included a total of 15 studies. Pooling data from 10 studies showed that prevalence for MinD in AD was 22.0% (95% CI 16.0 to 28.0). Prevalence for a clinical diagnosis of MinD (DSM-III-R and DSM-IV) was 26.0% (95% CI 20.0 to 32.0; 6 studies). People with MinD experienced higher levels of neuropsychiatric symptoms, functional and cognitive decline, although studies remain cross-sectional. Neither sertraline nor a carer intervention were effective in reducing symptoms. / Conclusion: This review finds that MinD is prevalent in people with a diagnosis of AD and requires clinical attention. Research is warranted to develop effective interventions to treat and prevent these symptoms

IDEA intervention to prevent depressive symptoms and promote well-being in early-stage dementia: protocol for a randomised controlled feasibility study

OBJECTIVE: Depressive symptoms are common among people with dementia, impacting quality of life and cognitive and functional decline. Currently, little is known about the acceptability and feasibility of psychological interventions for people with mild dementia, with recent reviews identifying the need for further evidence. Developing and evaluating psychological interventions to prevent and treat these symptoms is, therefore, an important clinical and research priority. This protocol describes a study testing the acceptability and feasibility of a manual-based behavioural activation (BA) intervention for preventing and treating depressive symptoms in people with mild dementia. The aim of this study is to explore the feasibility of conducting a pragmatic multicentre randomised controlled trial of clinical effectiveness of an eight-session intervention. The Intervention to prevent Depressive symptoms and promote well-being in EArly-stage dementia (IDEA) programme supports people with dementia and their family carers in identifying and scheduling enjoyable and meaningful activities. METHODS AND ANALYSIS: Sixty people who have received a diagnosis of dementia of any type in the last 6 months will be recruited via memory clinics. Further criteria are a Mini-Mental State Examination score of ≥20, and a family carer who can assist with the intervention. Consenting participants will be randomised in a ratio of 2:1 to BA or to treatment as usual. Analyses will estimate parameters such as rates of recruitment, retention and number of sessions completed. Questionnaires measuring depressive symptoms and quality of life for both the person with dementia and their carer will be completed at baseline, 3 and 6 months. Qualitative interviews will explore acceptability of the intervention, study procedures and experiences of the sessions. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the London Camberwell St Giles Research Ethics Committee (16/LO/0540). We will disseminate findings at key conferences, the Alzheimer’s Society and University College London websites and local stakeholder events. TRIAL REGISTRATION NUMBER: ISRCTN75503960; Pre-results

Synthesis, coordination study, and catalytic Pauson−Khand reactions of QuinoxP*(CO)4‑μ-alkyne dicobalt complexes

The coordination of the P-stereogenic and sterically demanding bisphosphine QuinoxP* to μ-alkyne dicobalt hexacarbonyl complexes was studied experimentally and computationally. Whereas the coordination occurred exclusively in a chelating fashion, the diastereoselectivity was highly substrate dependent. However, it could be explained from the computed structure and energies of the different coordination modes. The fluxional behavior of these complexes was also studied computationally. Their performance as catalysts for the Pauson−Khand reaction was explored, and outstanding reactivity was observed. Although the asymmetric induction was low to moderate, the stereochemical outcome could be mechanistically rationalized. This report provides promising results in terms of reactivity and mechanistic understanding for further developments of highly active chiral catalysts for intermolecular Pauson−Khand reactions

Exchange couplings in the magnetic molecular cluster Mn12Ac

The magnetic properties of the molecular cluster Mn12Ac are due to the four Mn3+ ions which have spins S=3/2 and the eight Mn4+ ions with spins S=2. These spins are coupled by superexchange mechanism. We determine the four exchange couplings assuming a Heisenberg-type interaction between the ions. We use exact diagonalization of the spin Hamiltonian by a Lanczos algorithm and we adjust the couplings to reproduce the magnetization curve of Mn12Ac. We also impose the constraint of reproducing a gap of 35K between a S=10 ground state and a first excited state with S=9. We predict that there is an excited level with S=8 at 37K above the ground state, only slightly above the S=9 excited state which lies at 35K and the next excited state is a S=9 multiplet at 67K above the S=10 ground state.Comment: 15 pages, 6 figures, submitted to Phys Rev B, corrected a misTeX: values of J1, J2 have changed, refs update

Development of a psychological intervention to promote meaningful activity in people living with mild dementia: an intervention mapping approach

Background and Objectives: Despite the importance of meaningful activity in mild dementia, only limited data are available on the development of interventions supporting people with mild dementia to engage in meaningful activity. In this article, we describe the development of an intervention that responds to this need. Research Design and Methods: Intervention mapping (IM), an evidence-based approach, was used to develop STAYING ACTIVE (STAYing well and active—schedulINg meaninGful and enjoyAble aCTIvities to promote Vitality and wEll-being in mild dementia). The first step, a needs assessment, comprised a literature review, focus groups, and individual interviews with service users. Performance objectives of the intervention were formulated in Step 2, followed by the development of theory-based methods in Step 3. In Step 4, the new intervention was developed based on data collected in previous steps, existing interventions, and pilot testing. Qualitative data were analyzed using framework analysis. Results: The needs assessment indicated that people with dementia and their carers view “staying active” as an important part of “enjoying life.” Adapting to loss through compensation and receiving support were key facilitators of engaging in meaningful activity. Ecological, psychosocial, and activity-oriented theories guided the development of theory-based intervention strategies, which were based on awareness, skills, and addressing barriers of meaningful activity. Discussion and Implications: STAYING ACTIVE is grounded on theory, and service user experiences and aims at promoting meaningful activity in mild dementia. The IM framework may be useful in the development of future psychosocial interventions for people with dementia, facilitating transparency when efficacy is evaluated

The T=1 capsid protein of Penicillium chrysogenum virus is formed by a repeated helix-rich core indicative of gene duplication

et al.Penicillium chrysogenum virus (PcV), a member of the Chrysoviridae family, is a double-stranded RNA (dsRNA) fungal virus with a multipartite genome, with each RNA molecule encapsidated in a separate particle. Chrysoviruses lack an extracellular route and are transmitted during sporogenesis and cell fusion. The PcV capsid, based on a T=1 lattice containing 60 subunits of the 982-amino-acid capsid protein, remains structurally undisturbed throughout the viral cycle, participates in genome metabolism, and isolates the virus genome from host defense mechanisms. Using three-dimensional cryoelectron microscopy, we determined the structure of the PcV virion at 8.0 Å resolution. The capsid protein has a high content of rod-like densities characteristic of α-helices, forming a repeated α-helical core indicative of gene duplication. Whereas the PcV capsid protein has two motifs with the same fold, most dsRNA virus capsid subunits consist of dimers of a single protein with similar folds. The spatial arrangement of the α-helical core resembles that found in the capsid protein of the L-A virus, a fungal totivirus with an undivided genome, suggesting a conserved basic fold. The encapsidated genome is organized in concentric shells; whereas the inner dsRNA shells are well defined, the outermost layer is dense due to numerous interactions with the inner capsid surface, specifically, six interacting areas per monomer. The outermost genome layer is arranged in an icosahedral cage, sufficiently well ordered to allow for modeling of an A-form dsRNA. The genome ordering might constitute a framework for dsRNA transcription at the capsid interior and/or have a structural role for capsid stability. Copyright © 2010, American Society for Microbiology. All Rights Reserved.This work was supported by grants from the Spanish Ministry of Science and Innovation (BFU 2008-02328/BMC and S-0505-Mat-0238 to J.L.C. and BIO2008-02361 to J.R.C.) and the NIH Intramural Research Program with support from the Center for Information Technology.Peer Reviewe