Sex and Socioeconomic Disparities in Dementia Risk: A Population Attributable Fractions Analysis in Argentina.

INTRODUCTION, twelve modifiable risk factors (RF) account for 40% of dementia cases worldwide. However, limited data exists on such factors in middle- and low-income countries. We aimed to estimate the population-attributable fractions (PAFs) for the 12 RF in Argentina, assessing changes over a decade, and exploring socioeconomic and sex influences. METHODS, we conducted cross-sectional analyses of the 12 RF from Argentinian surveys conducted in 2009, 2015, and 2018, including 96,321 people. We calculated PAFs, and stratified estimates based on sex and income. RESULTS, we estimated an overall PAF of 59.6%(95%CI=58.9%-60.3%). The largest PAFs were hypertension=9.3%(8.7%-9.9%), physical inactivity=7.4%(6.8%-8.2%), and obesity=7.4%(6.8%-7.9%). Men were more impacted by excessive alcohol, while women by isolation and smoking. Lower income linked to higher PAFs in education, hypertension, and obesity. DISCUSSION, Argentina has a higher PAF for dementia than the world population, with distinct RF distribution. PAF varied by sex and economic status, advocating tailored prevention strategies.

Potentially modifiable dementia risk factors in all Australians and within population groups: an analysis using cross-sectional survey data.

BACKGROUND: Dementia is the second leading cause of disease burden in Australia. We aimed to calculate the population attributable fractions (PAFs) of dementia attributable to 11 of 12 previously identified potentially modifiable health and social risk factors (less education, hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, diabetes, alcohol excess, air pollution, and traumatic brain injury), for Australians overall and three population groups (First Nations, and those of European and Asian ancestry). METHODS: We calculated the prevalence of dementia risk factors (excluding traumatic brain injury) and PAFs, adjusted for communality, from the cross-sectional National Aboriginal and Torres Strait Islander Health Survey (2018-19), National Aboriginal and Torres Strait Islander Social Survey (2014-15), National Health Survey (2017-18), and General Social Survey (2014) conducted by the Australian Bureau of Statistics. We conducted sensitivity analyses using proxy estimates for traumatic brain injury (12th known risk factor) for which national data were not available. FINDINGS: A large proportion (38·2%, 95% CI 37·2-39·2) of dementia in Australia was theoretically attributable to the 11 risk factors; 44·9% (43·1-46·7) for First Nations Australians, 36·4% (34·8-38·1) for European ancestry, and 33·6% (30·1-37·2) for Asian ancestry. Including traumatic brain injury increased the PAF to 40·6% (39·6-41·6) for all Australians. Physical inactivity (8·3%, 7·5-9·2), hearing loss (7·0%, 6·4-7·6), and obesity (6·6%, 6·0-7·3) accounted for approximately half of the total PAF estimates across Australia, and for all three population groups. INTERPRETATION: Our PAF estimates indicate a substantial proportion of dementia in Australia is potentially preventable, which is broadly consistent with global trends and results from other countries. The highest potential for dementia prevention was among First Nations Australians, reflecting the enduring effect of upstream social, political, environmental, and economic disadvantage, leading to greater life-course exposure to dementia risk factors. Although there were common dementia risk factors across different population groups, prevention strategies should be informed by community consultation and be culturally and linguistically appropriate. FUNDING: Australian National Health and Medical Research Council and University College London Hospitals' National Institute for Health Research (NIHR) Biomedical Research Centre, and North Thames NIHR Applied Research Collaboration.

Risk factors, ethnicity and dementia: A UK Biobank prospective cohort study of White, South Asian and Black participants.

BACKGROUND: Our knowledge of the effect of potentially modifiable risks factors on people developing dementia is mostly from European origin populations. We aimed to explore if these risk factors had similar effects in United Kingdom (UK) White, South Asian and Black UK Biobank participants recruited from 2006-2010 and followed up until 2020. METHODS: We reviewed the literature to 25.09.2020 for meta-analyses identifying potentially modifiable risk factors preceding dementia diagnosis by ≥10 years. We calculated prevalence of each identified risk factor and association with dementia for participants aged ≥55 at registration in UK Biobank. We calculated hazard ratios using Cox regression for each risk factor, stratified by ethnic group, and tested for differences using interaction effects between each risk factor and ethnicity. FINDINGS: We included education, hearing loss, hypertension, obesity, excess alcohol consumption, physical inactivity, smoking, high total cholesterol, depression, diabetes, social isolation, and air pollution as risks. Out of 294,162 participants, there were 287,806 White, 3590 South Asian and 2766 Black people, followed up for up to 14.8 years, with a total follow-up time of 3,392,095 years. During follow-up, 5,972 people (2.03%) developed dementia. Risk of dementia was higher in Black participants than White participants (HR for dementia compared to White participants as reference 1.43, 95% CI 1.16-1.77, p = 0.001) but South Asians had a similar risk. Association between each risk factor and dementia was similar in each ethnic group with no evidence to support any differences. INTERPRETATION: We find that Black participants were more likely to develop dementia than White participants, but South Asians were not. Identified risk factors in White European origin participants had a similar effect in Black and South Asian origin participants. Volunteers in UK Biobank are not representative of the population and interaction effects were underpowered so further work is needed.

Protection against discrimination in national dementia guideline recommendations: A systematic review.

BACKGROUND: National dementia guidelines provide recommendations about the most effective approaches to diagnosis and interventions. Guidelines can improve care, but some groups such as people with minority characteristics may be disadvantaged if recommended approaches are the same for everyone. It is not known if dementia guidelines address specific needs related to patient characteristics. The objectives of this review are to identify which countries have national guidelines for dementia and synthesise recommendations relating to protected characteristics, as defined in the UK Equality Act 2010: age, disability, gender identity, marriage and civil partnership, pregnancy and maternity, race, religion or belief, sex, and sexual orientation. METHODS AND FINDINGS: We searched CINAHL, PsycINFO, and Medline databases and the Guideline International Network library from inception to March 4, 2020, for dementia guidelines in any language. We also searched, between April and September 2020, Google and the national health websites of all 196 countries in English and in each country's official languages. To be included, guidelines had to provide recommendations about dementia, which were expected to be followed by healthcare workers and be approved at a national policy level. We rated quality according to the iCAHE guideline quality checklist. We provide a narrative synthesis of recommendations identified for each protected characteristic, prioritising those from higher-quality guidelines. Forty-six guidelines from 44 countries met our criteria, of which 18 were rated as higher quality. Most guidelines (39/46; 85%) made at least one reference to protected characteristics, and we identified recommendations relating to age, disability, race (or culture, ethnicity, or language), religion, sex, and sexual orientation. Age was the most frequently referenced characteristic (31/46; 67%) followed by race (or culture, ethnicity, or language; 25/46; 54%). Recommendations included specialist investigation and support for younger people affected by dementia and consideration of culture when assessing whether someone had dementia and providing person-centred care. Guidelines recommended considering religion when providing person-centred and end-of-life care. For disability, it was recommended that healthcare workers consider intellectual disability and sensory impairment when assessing for dementia. Most recommendations related to sex recommended not using sex hormones to treat cognitive impairment in men and women. One guideline made one recommendation related to sexual orientation. The main limitation of this study is that we only included national guidelines applicable to a whole country meaning guidelines from countries with differing healthcare systems within the country may have been excluded. CONCLUSIONS: National guidelines for dementia vary in their consideration of protected characteristics. We found that around a fifth of the world's countries have guidelines for dementia. We have identified areas of good practice that can be considered for future guidelines and suggest that all guidelines provide specific evidence-based recommendations for minority groups with examples of how to implement them. This will promote equity in the care of people affected by dementia and help to ensure that people with protected characteristics also have high-quality clinical services.

A cross-sectional study of potentially modifiable risk factors for dementia and cognitive function in India: A secondary analysis of 10/66, LASI, and SAGE data.

OBJECTIVES: Dementia is rising globally, particularly in low-and-middle-income countries. India has almost four million people living with dementia, set to double by 2050. Targeting nine potentially modifiable risk factors (less education, hearing impairment, depression, physical inactivity, hypertension, obesity, smoking, diabetes, and social isolation) could possibly prevent or delay many dementias. We aimed for the first time to examine risk factors for dementia in India and their link with cognitive status and dementia, to inform prioritisation of public health interventions that could prevent or delay dementia. METHODS: We conducted a cross-sectional analysis using three studies: 10/66 Dementia Study (n = 2004), Longitudinal Aging Study of India (n = 386), and Study of Global Ageing (n = 2441). Our exposures were the nine risk factors above. We calculated a cognitive z-score within each study and used dementia diagnosis in 10/66. We adjusted for socioeconomic factors, age, and sex using multivariable linear for cognition and logistic regression for dementia. RESULTS: Less education, hearing impairment, depression, and physical inactivity were associated with lower z-scores and increased odds of dementia. Obesity was associated with higher z-score and lower odds of dementia. Social isolation was associated with lower z-scores and decreased odds of dementia. Results for smoking, diabetes, and hypertension were inconsistent. CONCLUSION: Our risk estimates were larger for less education, hearing impairment and physical inactivity compared to global estimates and should be intervention priorities. This study highlights the need for longitudinal studies to clarify the relationship between these potentially modifiable risk factors and dementia in India.

Differences in the potential for dementia prevention between major ethnic groups within one country: A cross sectional analysis of population attributable fraction of potentially modifiable risk factors in New Zealand.

BACKGROUND: Twelve potentially modifiable risk factors (less education, hypertension, obesity, alcohol, traumatic brain injury (TBI), hearing loss, smoking, depression, physical inactivity, social isolation, diabetes, air pollution) account for an estimated 40% of worldwide dementia cases. We aimed to calculate population attributable fractions (PAFs) for dementia for the four largest New Zealand ethnic groups (European, Maori, Asian, and Pacific peoples) to identify whether optimal dementia prevention targets differed by ethnicity. METHODS: We calculated risk factor prevalence for 10 risk factors using the New Zealand Health Survey 2018/19 and published reports for hearing loss and TBI prevalences. We calculated the PAF for each risk factor using calculated prevalence and relative risk estimates from previous meta-analyses. To account for risk factor overlap, we calculated communality of risk factors and a weighted PAF. FINDINGS: The weighted PAF for dementia was 47.7% overall in New Zealand, 47.6% for Europeans, 51.4% for Maori, 50.8% for Pacific peoples, and 40.8% for Asians. Highest PAFs for Europeans were hearing loss (8%) and social isolation (5.7%), and for Asians hearing loss (7.3%) and physical inactivity (5.5%). For Maori and Pacific peoples, highest PAFs were for obesity (7.3% and 8.9% respectively) and hearing loss (6.5% and 6.6%). INTERPRETATION: New Zealand has higher dementia prevention potential than worldwide estimates with high prevalences of untreated hearing loss and obesity. The relative contribution of individual risk factors PAFs varies by ethnic group. Public health strategies for dementia prevention need to be tailored to these differences. FUNDING: Health Research Council of New Zealand (HRC:20/021).

Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies.

OBJECTIVES: To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association. DESIGN: Multicohort study with three sets of analyses. SETTING: United Kingdom, Europe, and the United States. PARTICIPANTS: Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies. MAIN OUTCOME MEASURES: Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations. RESULTS: During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I2=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted ß -0.34, P<0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted ß -0.33, P<0.001), and peptidyl-glycine α-amidating monooxygenase (AMD, fully adjusted ß -0.32, P<0.001). These proteins were associated with increased dementia risk, with the fully adjusted hazard ratio per 1 SD being 1.16 (95% confidence interval 1.05 to 1.28) for SLIT2, 1.13 (1.00 to 1.27) for CHSTC, and 1.04 (0.97 to 1.13) for AMD. CONCLUSIONS: The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings that cognitive stimulation is associated with lower levels of plasma proteins that potentially inhibit axonogenesis and synaptogenesis and increase the risk of dementia might provide clues to underlying biological mechanisms.

One third of dementia cases can be prevented within the next 25 years by tackling risk factors. The case "for" and "against".

BACKGROUND: Recently, it has been suggested that up to a third of the dementia cases might be preventable. While prevention is always better than cure, this is particularly important in the field of dementia, as current interventions are not able to modify the disease. This article revises the evidence "for" and "against" dementia primary prevention. DISCUSSION: Evidence "for" is sustained by the Lancet Commission on Dementia Prevention, Intervention and Care that noted a reduction of age-related incidence of dementia in high-income countries. Based on results from large cohort studies and using population attributable risk, the commission concluded that up to 35% of dementia cases could be prevented by modifying nine risk factors: low education, midlife hearing loss, obesity, hypertension, late-life depression, smoking, physical inactivity, diabetes, and social isolation. In this life course conceptual framework, modifications of risk factors can influence dementia decades before clinical disease onset. However, evidence "against" is supported by large randomized controlled trials (RCT, > 250 participants per arm, minimum of 6 months follow-up), primarily set to prevent dementia using lifestyle interventions that have shown modest or negative results. The 2017 National Academy of Medicine report concluded that the current evidence is limited and there are no specific interventions to warrant a public health recommendation for dementia prevention. Multiple pathological pathways are involved in the development of dementia which are theoretically treatable by managing midlife hearing loss and hypertension, and with physical exercise and education, as suggested by robust observational studies. However, evidence from large clinical trials is not conclusive to support that a third of dementia cases might be prevented. Current initiatives testing the effect of lifestyle interventions in larger clinical trials may help to settle this debate.

Effective interventions for potentially modifiable risk factors for late-onset dementia: a costs and cost-effectiveness modelling study.

BACKGROUND: The potential economic value of interventions to prevent late-onset dementia is unknown. We modelled this for potentially modifiable risk factors for dementia. METHODS: For this modelling study, we searched PubMed and Web of Science from inception to March 12, 2020, and included interventions that: successfully targeted any of nine prespecified potentially modifiable risk factors (hypertension, diabetes, hearing loss, obesity, physical inactivity, social isolation, depression, cigarette smoking, and less childhood education); had robust evidence that the intervention improved risk or risk behaviour; and are feasible to enact in an adult population. We established when in the life course each intervention would be delivered. We calculated dementia incidence reduction from annual incidence of dementia in people with each risk factor, and population attributable fraction for each risk, corrected for risk factor clustering, and how effectively the intervention controls the risk factor. We calculated the discounted value of lifetime health gain and effect on cost (including NHS, social care and carer costs) per person eligible for treatment. We estimated annual total expenditure on the fully operational intervention programme in England. FINDINGS: We found effective interventions for hypertension, smoking cessation, diabetes prevention, and hearing loss. Treatments for stopping smoking and provision of hearing aids reduced cost. Treatment of hypertension was cost-effective by reference to standard UK thresholds. The three interventions when fully implemented would save £1·863 billion annually in England, reduce dementia prevalence by 8·5%, and produce quality-adjusted life-year gains. The intervention for diabetes was unlikely to be cost-effective in terms of effect on dementia alone. INTERPRETATION: There is a strong case for implementing the three effective interventions on grounds of cost-effectiveness and quality-of-life gains, as well as for improvements in general health. The interventions have the potential to remain cost-saving or cost-effective even with variations in dementia incidence and costs and effectiveness of interventions. FUNDING: Economic and Social Research Council.

Hospitalisation rates and predictors in people with dementia: a systematic review and meta-analysis.

BACKGROUND: Hospitalisation is often harmful for people with dementia and results in high societal costs, so avoidance of unnecessary admissions is a global priority. However, no intervention has yet reduced admissions of community-dwelling people with dementia. We therefore aimed to examine hospitalisation rates of people with dementia and whether these differ from people without dementia and to identify socio-demographic and clinical predictors of hospitalisation. METHODS: We searched MEDLINE, Embase, and PsycINFO from inception to 9 May 2019. We included observational studies which (1) examined community-dwelling people with dementia of any age or dementia subtype, (2) diagnosed dementia using validated diagnostic criteria, and (3) examined all-cause general (i.e. non-psychiatric) hospital admissions. Two authors screened abstracts for inclusion and independently extracted data and assessed included studies for risk of bias. Three authors graded evidence strength using Cochrane's GRADE approach, including assessing for evidence of publication bias using Begg's test. We used random effects meta-analysis to pool estimates for hospitalisation risk in people with and without dementia. RESULTS: We included 34 studies of 277,432 people with dementia: 17 from the USA, 15 from Europe, and 2 from Asia. The pooled relative risk of hospitalisation for people with dementia compared to those without was 1.42 (95% confidence interval 1.21, 1.66) in studies adjusted for age, sex, and physical comorbidity. Hospitalisation rates in people with dementia were between 0.37 and 1.26/person-year in high-quality studies. There was strong evidence that admission is associated with older age, and moderately strong evidence that multimorbidity, polypharmacy, and lower functional ability are associated with admission. There was strong evidence that dementia severity alone is not associated. CONCLUSIONS: People with dementia are more frequently admitted to hospital than those without dementia, independent of physical comorbidities. Future interventions to reduce unnecessary hospitalisations should target potentially modifiable factors, such as polypharmacy and functional ability, in high-risk populations.

Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data.

BACKGROUND: Nine potentially modifiable risk factors (less childhood education, midlife hearing loss, hypertension, and obesity, and later-life smoking, depression, physical inactivity, social isolation, and diabetes) account for 35% of worldwide dementia, but most data to calculate these risk factors come from high-income countries only. We aimed to calculate population attributable fractions (PAFs) for dementia in selected low-income and middle-income countries (LMICs) to identify potential dementia prevention targets in these countries. METHODS: The study was an analysis of cross-sectional data obtained from the 10/66 Dementia Research surveys of representative populations in India, China, and six Latin America countries (Cuba, Dominican Republic, Mexico, Peru, Puerto Rico, and Venezuela), which used identical risk factor ascertainment methods in each country. Between 2004 and 2006 (and between 2007 and 2010 for Puerto Rico), all residents aged 65 years and older in predefined catchment areas were invited to participate in the survey. We used risk factor prevalence estimates from this 10/66 survey data, and relative risk estimates from previous meta-analyses, to calculate PAFs for each risk factor. To account for individuals having overlapping risk factors, we adjusted PAF for communality between risk factors, and used these values to calculate overall weighted PAFs for India, China, and the Latin American sample. FINDINGS: The overall weighted PAF for potentially modifiable risk factors for dementia was 39·5% (95% CI 37·5-41·6) in China (n=2162 participants), 41·2% (39·1-43·4) in India (n=2004), and 55·8% (54·9-56·7) in our Latin American sample (n=12 865). Five dementia risk factors were more prevalent in these LMICs than worldwide estimates, leading to higher PAFs for dementia: less childhood education (weighted PAF of 10·8% in China, 13·6% in India, and 10·9% in Latin America vs 7·5% worldwide), smoking (14·7%, 6·4%, and 5·7%, respectively, vs 5·5% worldwide), hypertension (6·4%, 4·0%, and 9·3%, vs 2·0%), obesity (5·6%, 2·9%, and 7·9%, vs 0·8%), and diabetes (1·6%, 1·7%, and 3·2%, vs 1·2%). INTERPRETATION: The dementia prevention potential in India, China, and this sample of Latin American countries is large, and greater than in high-income countries. Less education in early life, hypertension, hearing loss, obesity, and physical inactivity have particularly high PAFs and could be initial targets for dementia prevention strategies. FUNDING: No funding.

Amisulpride for very late-onset schizophrenia-like psychosis: the ATLAS three-arm RCT.

BACKGROUND: Very late-onset (aged ≥ 60 years) schizophrenia-like psychosis (VLOSLP) occurs frequently but no placebo-controlled, randomised trials have assessed the efficacy or risks of antipsychotic treatment. Most patients are not prescribed treatment. OBJECTIVES: The study investigated whether or not low-dose amisulpride is superior to placebo in reducing psychosis symptoms over 12 weeks and if any benefit is maintained by continuing treatment thereafter. Treatment safety and cost-effectiveness were also investigated. DESIGN: Three-arm, parallel-group, placebo-controlled, double-blind, randomised controlled trial. Participants who received at least one dose of study treatment were included in the intention-to-treat analyses. SETTING: Secondary care specialist old age psychiatry services in 25 NHS mental health trusts in England and Scotland. PARTICIPANTS: Patients meeting diagnostic criteria for VLOSLP and scoring > 30 points on the Brief Psychiatric Rating Scale (BPRS). INTERVENTION: Participants were randomly assigned to three arms in a two-stage trial: (1) 100 mg of amisulpride in both stages, (2) amisulpride then placebo and (3) placebo then amisulpride. Treatment duration was 12 weeks in stage 1 and 24 weeks (later reduced to 12) in stage 2. Participants, investigators and outcome assessors were blind to treatment allocation. MAIN OUTCOME MEASURES: Primary outcomes were psychosis symptoms assessed by the BPRS and trial treatment discontinuation for non-efficacy. Secondary outcomes were extrapyramidal symptoms measured with the Simpson-Angus Scale, quality of life measured with the World Health Organization's quality-of-life scale, and cost-effectiveness measured with NHS, social care and carer work loss costs and EuroQol-5 Dimensions. RESULTS: A total of 101 participants were randomised. Ninety-two (91%) participants took the trial medication, 59 (64%) completed stage 1 and 33 (56%) completed stage 2 treatment. Despite suboptimal compliance, improvements in BPRS scores at 12 weeks were 7.7 points (95% CI 3.8 to 11.5 points) greater with amisulpride than with placebo (11.9 vs. 4.2 points; p = 0.0002). In stage 2, BPRS scores improved by 1.1 point in those who continued with amisulpride but deteriorated by 5.2 points in those who switched from amisulpride to placebo, a difference of 6.3 points (95% CI 0.9 to 11.7 points; p = 0.024). Fewer participants allocated to the amisulpride group stopped treatment because of non-efficacy in stages 1 (p = 0.01) and 2 (p = 0.031). The number of patients stopping because of extrapyramidal symptoms and other side effects did not differ significantly between groups. Amisulpride treatment in the base-case analyses was associated with non-significant reductions in combined NHS, social care and unpaid carer costs and non-significant reductions in quality-adjusted life-years (QALYs) in both stages. Including patients who were intensive users of inpatient services in sensitivity analyses did not change the QALY result but resulted in placebo dominance in stage 1 and significant reductions in NHS/social care (95% CI -£8923 to -£122) and societal costs (95% CI -£8985 to -£153) for those continuing with amisulpride. LIMITATIONS: The original recruitment target of 300 participants was not achieved and compliance with trial medication was highly variable. CONCLUSIONS: Low-dose amisulpride is effective and well tolerated as a treatment for VLOSLP, with benefits maintained by prolonging treatment. Potential adverse events include clinically significant extrapyramidal symptoms and falls. FUTURE WORK: Trials should examine the longer-term effectiveness and safety of antipsychotic treatment in this patient group, and assess interventions to improve their appreciation of potential benefits of antipsychotic treatment and compliance with prescribed medication. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45593573 and EudraCT2010-022184-35. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 67. See the NIHR Journals Library website for further project information.

Use of a formal consensus development technique to produce recommendations for improving the effectiveness of adult mental health multidisciplinary team meetings.

BACKGROUND: Multidisciplinary team (MDT) meetings are the core mechanism for delivering mental health care but it is unclear which models improve care quality. The aim of the study was to agree recommendations for improving the effectiveness of adult mental health MDT meetings, based on national guidance, research evidence and experiential insights from mental health and other medical specialties. METHODS: We established an expert panel of 16 health care professionals, policy-makers and patient representatives. Five panellists had experience in a range of adult mental health services, five in heart failure services and six in cancer services. Panellists privately rated 68 potential recommendations on a scale of one to nine, and re-rated them after panel discussion using the RAND/UCLA Appropriateness Method to determine consensus. RESULTS: We obtained agreement (median ≥ 7) and low variation in extent of agreement (Mean Absolute Deviation from Median of ≤1.11) for 21 recommendations. These included the explicit agreement and auditing of MDT meeting objectives, and the documentation and monitoring of treatment plan implementation. CONCLUSIONS: Formal consensus development methods that involved learning across specialities led to feasible recommendations for improved MDT meeting effectiveness in a wide range of settings. Our findings may be used by adult mental health teams to reflect on their practice and facilitate improvement. In some other contexts, the recommendations will require modification. For example, in Child and Adolescent Mental Health Services, context-specific issues such as the role of carers should be taken into account. A limitation of the comparative approach adopted was that only five members of the panel of 16 experts were mental health specialists.

A systematic review of interventions to detect dementia or cognitive impairment.

BACKGROUND: Memory services have been implemented nationally to increase early dementia diagnosis, and further evaluation of their impact and other strategies to increase timely dementia diagnosis are needed. AIMS: To systematically review the literature for interventions intended to increase the detection of dementia or suspected dementia or people presenting with memory complaints. METHOD: We searched electronic databases, hand searched references and contacted authors of included papers, contacted field experts and UK charities and councils for data about their dementia awareness programmes. RESULTS: We included 13 studies, of which four were randomised controlled trials (RCT). Two RCTs found that general practitioner (GP) education increased suspected dementia cases. One RCT found up to six home visits from a specialist geriatric nurse over 30 months increased the rate of accurately diagnosed dementia. There was preliminary evidence from non-randomised studies that memory clinics increase timely diagnosis, but no evidence they increase the overall diagnosis rate. CONCLUSIONS: There is good quality evidence that GP education increases the number of suspected dementia cases but not accurate or earlier dementia diagnoses. One RCT reported that multiple visits from a trained nurse increase the diagnosis rate. There is no cost effectiveness evidence. Our findings suggest good quality RCTs are needed to test the effectiveness and cost-effectiveness of interventions to increase dementia detection.

Treatment for mild cognitive impairment: systematic review.

BACKGROUND: More people are presenting with mild cognitive impairment (MCI), frequently a precursor to dementia, but we do not know how to reduce deterioration. AIMS: To systematically review randomised controlled trials (RCTs) evaluating the effects of any intervention for MCI on cognitive, neuropsychiatric, functional, global outcomes, life quality or incident dementia. METHOD: We reviewed 41 studies fitting predetermined criteria, assessed validity using a checklist, calculated standardised outcomes and prioritised primary outcome findings in placebo-controlled studies. RESULTS: The strongest evidence was that cholinesterase inhibitors did not reduce incident dementia. Cognition improved in single trials of: a heterogeneous psychological group intervention over 6 months; piribedil, a dopamine agonist over 3 months; and donepezil over 48 weeks. Nicotine improved attention over 6 months. There was equivocal evidence that Huannao Yicong improved cognition and social functioning. CONCLUSIONS: There was no replicated evidence that any intervention was effective. Cholinesterase inhibitors and rofecoxib are ineffective in preventing dementia. Further good-quality RCTs are needed and preliminary evidence suggests these should include trials of psychological group interventions and piribedil.

A systematic review of treatments for refractory depression in older people.

OBJECTIVE: The authors systematically reviewed the management of treatment-refractory depression in older people (defined as age 55 or older). METHOD: The authors conducted an electronic database search and reviewed the 14 articles that fit predetermined criteria. Refractory depression was defined as failure to respond to at least one course of treatment for depression during the current illness episode. The authors rated the validity of studies using a standard checklist and calculated the pooled proportion of response to any treatment reported by at least three studies. RESULTS: All the studies that met inclusion criteria investigated pharmacological treatment. Most were open-label studies, and the authors found no double-blind randomized placebo-controlled trials. The overall response rate for all active treatments investigated was 52% (95% CI=42-62; N=381). Only lithium augmentation was assessed in more than two trials, and the response rate was 42% (95% CI=21-65; N=57). Only two studies included comparison groups receiving no additional treatment, and none of the participants in these groups responded. In single randomized studies, extended-release venlafaxine was more efficacious than paroxetine, lithium augmentation more than phenelzine, and selegiline more than placebo. CONCLUSIONS: Half of the participants responded to pharmacological treatments, indicating the importance of managing treatment-refractory depression actively in older people. The only treatment for which there was replicated evidence was lithium augmentation. Double-blind randomized controlled trials for management of treatment-refractory depression in older people, encompassing pharmacological and nonpharmacological therapies and populations that reflect the levels of physical and cognitive impairment present in the general older population with depression, are needed.

Making decisions for people with dementia who lack capacity: qualitative study of family carers in UK.

OBJECTIVE: To identify common difficult decisions made by family carers on behalf of people with dementia, and facilitators of and barriers to such decisions, in order to produce information for family carers about overcoming barriers. DESIGN: Qualitative study to delineate decision areas through focus groups and complexity of decision making in individual interviews. SETTING: Community settings in London. PARTICIPANTS: 43 family carers of people with dementia in focus groups and 46 carers who had already made such decisions in individual interviews. RESULTS: Family carers identified five core problematic areas of decision making: accessing dementia related health and social services; care homes; legal-financial matters; non-dementia related health care; and making plans for the person with dementia if the carer became too ill to care for them. They highlighted the difficulties in making proxy decisions, especially against active resistance, and their altered role of patient manager while still a family member. Families devised strategies to gain agreement in order to ensure that the person with dementia retained dignity. CONCLUSIONS: The following strategies helped with implementation of decisions: introducing change slowly; organising legal changes for the carer as well as the patient; involving a professional to persuade the patient to accept services; and emphasising that services optimised, not impeded, independence. To access services, carers made patients' general practice appointments, accompanied them to the surgery, pointed out symptoms, gained permission to receive confidential information, asked for referral to specialist services, and used professionals' authority to gain patients' agreement. End of life decisions were particularly difficult. They were helped by knowledge of the person with dementia's previous views, clear prognostic information, and family support. Information sheets to help carers to overcome barriers to proxy decision making have been developed; their impact in practice has yet to be evaluated.

The sensitivity and specificity of the Modified Conflict Tactics Scale for detecting clinically significant elder abuse.

BACKGROUND: A third of family carers of people with dementia describe acting abusively in research studies, but far fewer cases of abuse are currently detected in clinical situations. This discrepancy may be explained by inadequate detection by health professionals, or disagreement regarding what constitutes elder abuse. This study was undertaken to determine the sensitivity and specificity of the revised Modified Conflict Tactics Scale (MCTS) for detecting clinically significant abuse. METHODS: We interviewed 220 family carers of people consecutively referred to psychiatric services with dementia in Essex and London (U.K.), using the MCTS to measure abuse. We defined abuse cases using (1) the MCTS conventional scoring system; (2) the Pillemer criteria; and (3) clinical judgment of an expert panel. RESULTS: Our panel judged that 15 (6.8%) of carers reported potentially clinical concerning abusive behavior; but 47 (21%) were cases according to the Pillemer criteria and 74 (34%) using the MCTS conventional scoring system. We developed a weighted MCTS scoring system, with high sensitivity and specificity for detecting clinically concerning abuse. CONCLUSIONS: The MCTS could be used routinely in clinical practice with carers of people with dementia to detect clinically concerning cases of abuse, many of which are currently being missed.

Prediction of survival in Alzheimer's disease--the LASER-AD longitudinal study.

OBJECTIVES: Alzheimer's disease (AD) is associated with variable but shortened life expectancy. Knowing expected survival time may empower people with AD and their families, but clinicians currently have limited predictive information. Our objective was to identify determinants of survival in a cohort of people with mild to moderate AD and test these on a separate validation cohort. METHODS: We followed a representative cohort of 158 people for 42 months and identified independent determinants of shorter survival. From these we constructed the Survival in Alzheimer's Model (SAM), and tested this on a validation cohort. RESULTS: Baseline constructional apraxia, age and gait apraxia independently predicted shorter survival: about half of those scoring 2 on the SAM survived > or =3.5 years compared to 85% of those scoring 0. CONCLUSIONS: The SAM is a potentially useful tool for clinicians who previously had very limited specific and quantitative prognostic information to tell AD patients and carers. This model predicted survival from age, constructional and gait apraxia. This may be because constructional and gait apraxia are relatively free from educational or cultural bias and thus are better indicators of severe neuropathology than global cognitive tests. Alternatively, they may increase falls or immobility, or represent disease sub-types with worse prognoses. Oncology services are able to inform patients and their families about 5-year survival rates. This step towards such provision in AD is new and of potential importance to patients and their carers.

Indicators of elder abuse: a crossnational comparison of psychiatric morbidity and other determinants in the Ad-HOC study.

OBJECTIVE: The objective of this study was to determine crossnationally the prevalence of indicators of elder abuse and their relationship to putative risk factors, particularly depression, dementia, and lack of service provision. METHOD: Nearly 4,000 people aged 65+ receiving health or social community services in 11 European countries were interviewed using the minimum dataset homecare (MDS-HC) interview, which includes an abuse screen used previously in elder abuse studies and questions about demographic, physical, psychiatric, cognitive, and service factors. RESULTS: One hundred seventy-nine (4.6%) people assessed had at least one indicator of abuse. The proportion screening positive increased with severity of cognitive impairment, presence of depression, delusions, pressure ulcers, actively resisting care, less informal care, expressed conflict with family or friends, or living in Italy or Germany, but not with having a known psychiatric diagnosis. CONCLUSION: Severity of cognitive impairment, depression, and delusions predicted screening positive for abuse in older adults, but having a known psychiatric diagnosis did not, indicating that screening for psychiatric morbidity might be rational strategies to combat elder abuse. People in Italy and Germany were most likely to screen positive for indicators of abuse, and the authors suggest that this might relate to higher levels of dependency in the participants looked after at home in these countries as a result of cultural and service provision differences.