Public perceptions about risk and protective factors for cognitive health and impairment: a review of the literature

ABSTRACT Background: Preventing and/or delaying cognitive impairment is a public health priority. To increase awareness of and participation in behaviors that may help maintain cognitive function or reduce risk of impairment, we need to understand public perceptions about risk and protective factors. Methods: We conducted a scoping review of studies examining the public's perceptions about risk and protective factors related to cognitive health and impairment published since the 2007 National Public Health Road Map to Maintaining Cognitive Health . Results: A search of five databases yielded 1,115 documents published between June 2007 and December 2013. Initial review of abstracts identified 90 potentially eligible studies. After full-article review, 30 met inclusion criteria; four additional articles identified in reference lists also met inclusion criteria. Of the 34, 16 studies addressed Alzheimer's disease (AD) specifically, 15 dementia broadly, 5 mild to moderate cognitive impairment, and 8 normal functioning, with some content overlap. Across studies, respondents reported genetics ( n = 14 studies), older age ( n = 8), stress ( n = 7), brain/head injury ( n = 6), and mental illness/brain disease ( n = 6) as perceived risk factors for AD and dementia. Protective factors most commonly identified for maintaining cognitive health were intellectual/mental stimulation ( n = 13), physical activity ( n = 12), healthy diet ( n = 10), and social/leisure activities ( n = 10). Conclusions: Studies identified genetics and older age as key perceived risk factors more so than behaviors such as smoking. Individuals perceived that numerous lifestyle factors (e.g. intellectual stimulation, physical activity) could protect against cognitive impairment, AD, and/or dementia. Results can inform national and international education efforts about AD and other dementias

Evaluating the effectiveness and cost-effectiveness of Dementia Care Mapping™ to enable person-centred care for people with dementia and their carers (DCM-EPIC) in care homes: study protocol for a randomised controlled trial

Background Up to 90 % of people living with dementia in care homes experience one or more behaviours that staff may describe as challenging to support (BSC). Of these agitation is the most common and difficult to manage. The presence of agitation is associated with fewer visits from relatives, poorer quality of life and social isolation. It is recommended that agitation is treated through psychosocial interventions. Dementia Care Mapping™ (DCM™) is an established, widely used observational tool and practice development cycle, for ensuring a systematic approach to providing person-centred care. There is a body of practice-based literature and experience to suggests that DCM™ is potentially effective but limited robust evidence for its effectiveness, and no examination of its cost-effectiveness, as a UK health care intervention. Therefore, a definitive randomised controlled trial (RCT) of DCM™ in the UK is urgently needed. Methods/design A pragmatic, multi-centre, cluster-randomised controlled trial of Dementia Care Mapping (DCM™) plus Usual Care (UC) versus UC alone, where UC is the normal care delivered within the care home following a minimum level of dementia awareness training. The trial will take place in residential, nursing and dementia-specialist care homes across West Yorkshire, Oxfordshire and London, with residents with dementia. A random sample of 50 care homes will be selected within which a minimum of 750 residents will be registered. Care homes will be randomised in an allocation ratio of 3:2 to receive either intervention or control. Outcome measures will be obtained at 6 and 16 months following randomisation. The primary outcome is agitation as measured by the Cohen-Mansfield Agitation Inventory, at 16 months post randomisation. Key secondary outcomes are other BSC and quality of life. There will be an integral cost-effectiveness analysis and a process evaluation. Discussion The protocol was refined following a pilot of trial procedures. Changes include replacement of a questionnaire, whose wording caused some residents distress, to an adapted version specifically designed for use in care homes, a change to the randomisation stratification factors, adaption in how the staff measures are collected to encourage greater compliance, and additional reminders to intervention homes of when mapping cycles are due, via text message. Trial registration Current Controlled Trials ISRCTN82288852. Registered on 16 January 2014. Full protocol version and date: v7.1: 18 December 2015

A Variational Bayes Discrete Mixture Test for Rare Variant Association

Recently, many statistical methods have been proposed to test for associations between rare genetic variants and complex traits. Most of these methods test for association by aggregating genetic variations within a predefined region, such as a gene. Although there is evidence that “aggregate” tests are more powerful than the single marker test, these tests generally ignore neutral variants and therefore are unable to identify specific variants driving the association with phenotype. We propose a novel aggregate rare-variant test that explicitly models a fraction of variants as neutral, tests associations at the gene-level, and infers the rare-variants driving the association. Simulations show that in the practical scenario where there are many variants within a given region of the genome with only a fraction causal our approach has greater power compared to other popular tests such as the Sequence Kernel Association Test (SKAT), the Weighted Sum Statistic (WSS), and the collapsing method of Morris and Zeggini (MZ). Our algorithm leverages a fast variational Bayes approximate inference methodology to scale to exome-wide analyses, a significant computational advantage over exact inference model selection methodologies. To demonstrate the efficacy of our methodology we test for associations between von Willebrand Factor (VWF) levels and VWF missense rare-variants imputed from the National Heart, Lung, and Blood Institute’s Exome Sequencing project into 2,487 African Americans within the VWF gene. Our method suggests that a relatively small fraction (~10%) of the imputed rare missense variants within VWF are strongly associated with lower VWF levels in African Americans

Imputation of Exome Sequence Variants into Population- Based Samples and Blood-Cell-Trait-Associated Loci in African Americans: NHLBI GO Exome Sequencing Project

Researchers have successfully applied exome sequencing to discover causal variants in selected individuals with familial, highly penetrant disorders. We demonstrate the utility of exome sequencing followed by imputation for discovering low-frequency variants associated with complex quantitative traits. We performed exome sequencing in a reference panel of 761 African Americans and then imputed newly discovered variants into a larger sample of more than 13,000 African Americans for association testing with the blood cell traits hemoglobin, hematocrit, white blood count, and platelet count. First, we illustrate the feasibility of our approach by demonstrating genome-wide-significant associations for variants that are not covered by conventional genotyping arrays; for example, one such association is that between higher platelet count and an MPL c.117G>T (p.Lys39Asn) variant encoding a p.Lys39Asn amino acid substitution of the thrombpoietin receptor gene (p = 1.5 × 10−11). Second, we identified an association between missense variants of LCT and higher white blood count (p = 4 × 10−13). Third, we identified low-frequency coding variants that might account for allelic heterogeneity at several known blood cell-associated loci: MPL c.754T>C (p.Tyr252His) was associated with higher platelet count; CD36 c.975T>G (p.Tyr325∗) was associated with lower platelet count; and several missense variants at the α-globin gene locus were associated with lower hemoglobin. By identifying low-frequency missense variants associated with blood cell traits not previously reported by genome-wide association studies, we establish that exome sequencing followed by imputation is a powerful approach to dissecting complex, genetically heterogeneous traits in large population-based studies

Functional mobility limitations and falls in assisted living residents with dementia: physical performance assessment and quantitative gait analysis

Background and Purpose: The prevalence of functional mobility limitations and falls is higher in people with dementia compared with cognitively healthy older adults, and both are associated with gait and motor impairments. The aims of this study were to examine concurrent validity of physical performance assessments and spatiotemporal gait measures in older adults with advanced dementia and to prospectively examine their relationship to functional mobility limitations and falls over a 4-month period.Methods: Thirty-one older adults living in dementia-specific assisted living residences participated. Correlations were examined between a modified Berg Balance Scale (mod-Berg), the Short Physical Performance Battery (SPPB), and spatiotemporal gait measures using the GAITRite Walkway system. Over 4-months, functional mobility limitations were rated, and falls were recorded by nursing supervisors. Differences in functional mobility limitations and falls were examined in relation to baseline balance and gait measures.Results: Partial correlations between spatiotemporal gait measures and the mod-Berg as well as the SPPB were statistically significant (P < .05) after adjusting for age and Mini-Mental State Examination scores. Participants with low functional mobility ratings had significantly lower scores on the mod-Berg (