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.

Scaling-up an evidence-based intervention for family carers of people with dementia: Current and future costs and outcomes.

OBJECTIVES: The STrAtegies for RelaTives (START) intervention is effective and cost-effective in supporting family carers of people with dementia. It is currently not available to all eligible carers in England. What would be the impacts on service costs and carer health-related quality of life if START was provided to all eligible carers in England, currently and in future? METHODS: Effectiveness and cost-effectiveness data from a previously conducted randomised controlled trial were combined with current and future projections of numbers of people with newly diagnosed dementia to estimate overall and component costs and health-related quality of life outcomes between 2015 (base year for projections) and 2040. RESULTS: Scaling-up START requires investments increasing annually but would lead to significant savings in health and social care costs. Family carers of people with dementia would experience improvements in mental health and quality of life, with clinical effects lasting at least 6 years. Scaling up the START intervention to eligible carers was estimated to cost £9.4 million in 2020, but these costs would lead to annual savings of £68 million, and total annual quality-adjusted life year (QALY) gains of 1247. Although the costs of START would increase to £19.8 million in 2040, savings would rise to £142.7 million and Quality adjusted life years gained to 1883. CONCLUSIONS: Scaling-up START for family carers of people with dementia in England would improve the lives of family carers and reduce public sector costs. Family carers play a vital part in dementia care; evidence-based interventions that help them to maintain this role, such as START, should be available across the country.

Bi-directional association between outdoor or social activities and cognitive function: do the PM2.5 exposure catalyze the detrimental inactivity-poor cognition cycle?

BACKGROUND: Previous research has shown that lack of leisure activities, either outdoor or social activities, impedes cognitive function. However, the interrelationship between poor cognition and deficient activities is understudied. In addition, whether exposure to air pollution, such as PM2.5, can accelerate the detrimental 'inactivity-poor cognition' cycle, is worthy of investigation. METHODS: We used data from the 2008, 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We assessed the frequency of outdoor or social activities at each wave. The cognitive function was examined using a China-Modified Mini-mental State Examination. We estimated the residential exposure to fine particular matter (PM2.5) via a satellite-based model. We applied cross-lagged panel (CLP) model to examine the bi-directional relationship between outdoor or social activities and cognitive function. We then examined the effect of PM2.5 exposure with sequent cognitive function and activities using generalized estimation equation (GEE) model. FINDINGS: Overall, we observed significant bi-directional associations between outdoor or social activities and cognitive function. Participants with better cognitive function in the last wave were more likely to engage in outdoor or social activities in the following wave (outdoor activities: ß = 0.37, 95% CI [0.27,0.48], P < 0.01; social activities: ß = 0.05, 95% CI [0.02,0.09] P < 0.01). Meanwhile, higher engagement in outdoor or social activities in the last wave was associated with more favorable cognitive function in the following wave (outdoor activities: ß = 0.06, 95% CI [0.03,0.09], P < 0.01; social activities: ß = 0.10, 95% CI [0.03,0.18], P < 0.01). Notably, an increase in PM2.5 exposure during the preceding year was significantly associated with a declining cognitive function (ß = -0.05, 95% CI [-0.08,-0.03], P < 0.01), outdoor activities (ß = -0.02, 95% CI [-0.04, -0.01], P < 0.01) and social activities (ß = -0.02, 95% CI [-0.02, -0.01], P < 0.01) in the current year; the lagged effects of the PM2.5 exposure in the past year of the last wave on activities and cognitive function of the following wave were also observed. INTERPRETATION: Our findings not only indicate the bi-directional links between the frequency of outdoor or social activities and cognitive function, but also report that PM2.5 exposure plays a role in catalyzing the detrimental inactivity-poor cognition cycle. Future research should investigate whether the policy-driven interventions, such as clean air policies, can break the unfavorable activity-cognition cycle, and thereby promoting health from the dual gains in leisure activities and cognition.

Risk assessment for people living with dementia: a systematic review.

OBJECTIVE: This systematic review identified key components of risk assessment for people with dementia, examined attitudes toward risk identification and risk assessment, and appraised existing risk assessment tools. METHODS: Systematic searches of five databases on two platforms (EBSCO, OVID) and gray literature databases (Open Grey, Base) were conducted. Studies were screened for inclusion based on predetermined eligibility criteria and quality assessed using the Mixed Methods Appraisal Tool. Findings were tabulated and synthesized using thematic synthesis. RESULTS: Our review found people with dementia, their family carers, and healthcare professionals differed in how risk is conceptualized, with views being shaped by media perceptions, personal experiences, socio-cultural influences, dementia knowledge, and dementia severity. We found that mobilization (causing falls inside and getting lost outside) is the most frequently identified risk factor. Our findings show people with dementia are generally risk-tolerant, while healthcare professionals may adopt risk-averse approaches because of organizational requirements. We found factors that disrupt daily routines, living and caring arrangements, medication management, and unclear care pathways contribute toward adverse risk events. We discovered that most studies about risk and risk assessment scales did not consider insight of the person with dementia into risks although this is important for the impact of a risk. No risk instrument identified had sufficient evidence that it was useful. CONCLUSION: Accurate risk assessment and effective communication strategies that include the perspectives of people with dementia are needed to enable risk-tolerant practice. No risk instrument to date was shown to be widely acceptable and useful in practice.

Validation of the Japanese version of the Social Functioning in Dementia scale and COVID-19 pandemic's impact on social function in mild cognitive impairment and mild dementia.

OBJECTIVES: We aimed to psychometrically evaluate and validate a Japanese version of the Social Functioning in Dementia scale (SF-DEM-J) and investigate changes in social function in people with dementia during the coronavirus disease-19 (COVID-19) pandemic. DESIGN: We interviewed people with mild cognitive impairment (MCI) and mild dementia and their caregivers during June 2020-March 2021 to validate patient- and caregiver-rated SF-DEM-J and compared their scores at baseline (April 2020 to May 2020) and at 6-8 months (January 2021 to March 2021) during a time of tighter COVID-19 restrictions. SETTING: The neuropsychology clinic in the Department of Psychiatry at Osaka University Hospital and outpatient clinic in the Department of Psychiatry and Neurology at Daini Osaka Police Hospital, Japan. PARTICIPANTS: 103 dyads of patients and caregivers. MEASUREMENTS: SF-DEM-J, Mini-Mental State Examination, Neuropsychiatric Inventory, UCLA Loneliness Scale, and Apathy Evaluation Scale. RESULTS: The scale's interrater reliability was excellent and test-retest reliability was substantial. Content validity was confirmed for the caregiver-rated SF-DEM-J, and convergent validity was moderate. Caregiver-rated SF-DEM-J was associated with apathy, irritability, loneliness, and cognitive impairment. The total score of caregiver-rated SF-DEM-J and the score of Section 2, "communication with others," significantly improved at 6-8 months of follow-up. CONCLUSIONS: The SF-DEM-J is acceptable as a measure of social function in MCI and mild dementia. Our results show that the social functioning of people with dementia, especially communicating with others, improved during the COVID-19 pandemic, probably as a result of adaptation to the restrictive life.

A longitudinal cohort study on the use of health and care services by older adults living at home with/without dementia before and during the COVID-19 pandemic: the HUNT study.

BACKGROUND: Older adults and people with dementia were anticipated to be particularly unable to use health and care services during the lockdown period following the COVID-19 pandemic. To better prepare for future pandemics, we aimed to investigate whether the use of health and care services changed during the pandemic and whether those at older ages and/or dementia experienced a higher degree of change than that observed by their counterparts. METHODS: Data from the Norwegian Trøndelag Health Study (HUNT4 70 + , 2017-2019) were linked to two national health registries that have individual-level data on the use of primary and specialist health and care services. A multilevel mixed-effects linear regression model was used to calculate changes in the use of services from 18 months before the lockdown, (12 March 2020) to 18 months after the lockdown. RESULTS: The study sample included 10,607 participants, 54% were women and 11% had dementia. The mean age was 76 years (SD: 5.7, range: 68-102 years). A decrease in primary health and care service use, except for contact with general practitioners (GPs), was observed during the lockdown period for people with dementia (p < 0.001) and those aged ≥ 80 years without dementia (p = 0.006), compared to the 6-month period before the lockdown. The use of specialist health services decreased during the lockdown period for all groups (p ≤ 0.011), except for those aged < 80 years with dementia. Service use reached levels comparable to pre-pandemic data within one year after the lockdown. CONCLUSION: Older adults experienced an immediate reduction in the use of health and care services, other than GP contacts, during the first wave of the COVID-19 pandemic. Within primary care services, people with dementia demonstrated a more pronounced reduction than that observed in people without dementia; otherwise, the variations related to age and dementia status were small. Both groups returned to services levels similar to those during the pre-pandemic period within one year after the lockdown. The increase in GP contacts may indicate a need to reallocate resources to primary health services during future pandemics. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov, with the identification number NCT04792086.

Umbrella review and Delphi study on modifiable factors for dementia risk reduction.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.

Adapted problem adaptation therapy for depression in mild to moderate Alzheimer's disease dementia: A randomized controlled trial.

INTRODUCTION: Trials of effectiveness of treatment options for depression in dementia are an important priority. METHODS: Randomized controlled trial to assess adapted Problem Adaptation Therapy (PATH) for depression in mild/moderate dementia caused by Alzheimer's disease. RESULTS: Three hundred thirty-six participants with mild or moderate dementia, >7 on Cornell Scale for Depression in Dementia (CSDD), randomized to adapted PATH or treatment as usual. Mean age 77.0 years, 39.0% males, mean Mini-Mental State Examination 21.6, mean CSDD 12.9. For primary outcome (CSDD at 6 months), no statistically significant benefit with adapted PATH on the CSDD (6 months: -0.58; 95% CI -1.71 to 0.54). The CSDD at 3 months showed a small benefit with adapted PATH (-1.38; 95% CI -2.54 to -0.21) as did the EQ-5D (-4.97; 95% CI -9.46 to -0.48). DISCUSSION: An eight-session course of adapted PATH plus two booster sessions administered within NHS dementia services was not effective treatment for depression in people with mild and moderate dementia. Future studies should examine the effect of more intensive and longer-term therapy.

The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Insomnia and risk of dementia in a large population-based study with 11-year follow-up: The HUNT study.

Despite evidence suggesting that insomnia is associated with the risk of dementia and cognitive dysfunction, studies have shown mixed results. Dementia has a long prodromal phase, and studies with long follow-up are required to avoid reverse causality. In our 11-year follow-up study, we assessed whether probable insomnia disorder (PID) based on diagnostic criteria, and insomnia symptoms were associated with risk of all-cause dementia, Alzheimer's disease (AD) and cognition, measured with the Montreal Cognitive Assessment scale. We also examined if Apolipoprotein E genotype modified any associations with dementia through interaction. We analysed data from 7492 participants in the Norwegian Trøndelag Health Study. PID was not associated with all-cause dementia (odds ratio = 1.03, 95% confidence interval = 0.74-1.43), AD (odds ratio = 1.07, 95% confidence interval = 0.71-1.60) or Montreal Cognitive Assessment score (regression coefficient = 0.37, 95% confidence interval = -0.06 to 0.80). The insomnia symptom "difficulties maintaining sleep" was associated with a lower risk of all-cause dementia (odds ratio = 0.81, 95% confidence interval = 0.67-0.98), AD (odds ratio = 0.73, 95% confidence interval = 0.57-0.93), and better Montreal Cognitive Assessment score, mean 0.40 units (95% confidence interval = 0.15-0.64). No interaction with Apolipoprotein E genotype was found. PID and insomnia symptoms did not increase the risk of dementia in our study. More research with longer follow-up is needed, and future studies should explore if the associations to dementia risk vary across insomnia subtypes.

Tailoring STrAtegies for RelaTives for Black and South Asian dementia family carers in the United Kingdom: A mixed methods study.

OBJECTIVES: We culturally adapted STrAtegies for RelaTives (START), a clinically and cost-effective intervention for dementia family carers, for Black and South Asian families. It had previously been delivered to family carers around the time of diagnosis, when most people with dementia had very mild, mild or moderate dementia. METHODS: We interviewed a maximum variation sample of family carers (phase one; n = 15 South Asian; n = 11 Black) about what aspect of START, required cultural adaptation, then analysed it thematically using the Cultural Treatment Adaptation Framework then adapted it in English and into Urdu. Facilitators then delivered START individually to carers (phase two; n = 13 South Asian; n = 8 Black). We assessed acceptability and feasibility through the number of sessions attended, score for fidelity to the intervention and interviewing family carers about their experiences. We used the Hospital Anxiety and Depression Scale. to examine whether immediate changes in family carers' mental health were in line with previous studies. RESULTS: In phase one we made adaptations to peripheral elements of START, clarifying language, increasing illustrative vignettes numbers, emphasising privacy and the facilitator's cultural competence and making images ethnically diverse. In phase two 21 family carers consented to receive the adapted intervention; 12 completed ≥5/8 sessions; four completed fewer sessions and five never started. Baseline HADS score (n = 21) was 14.4 (SD = 9.8) but for those who we were able to follow up was 12.3 (SD 8.1) and immediately post-intervention was 11.3 (n = 10; SD = 6.1). Family carers were positive about the adapted START and continued to use elements after the intervention. CONCLUSIONS: Culturally adapted START was acceptable and feasible in South Asian and Black UK-based family carers and changes in mental health were in line with those in the original clinical trial. Our study shows that culturally inclusive START was also acceptable. Changes made in adaptations were relevant to all populations. We now use the adapted version for all family carers irrespective of ethnicity.

Equity in care and support provision for people affected by dementia: experiences of people from UK South Asian and White British backgrounds.

OBJECTIVES: To explore the care and support received and wanted by United Kingdom (UK) South Asian and White British people affected by dementia and whether access to it is equitable. DESIGN: Semi-structured interviews using a topic guide. SETTING: Eight memory clinics across four UK National Health Service Trusts; three in London and one in Leicester. PARTICIPANTS: We purposefully recruited a maximum variation sample of people living with dementia from South Asian or White British backgrounds, their family carers, and memory clinic clinicians. We interviewed 62 participants including 13 people living with dementia, 24 family carers, and 25 clinicians. MEASUREMENTS: We audio-recorded interviews, transcribed them, and analyzed them using reflexive thematic analysis. RESULTS: People from either background were willing to accept needed care and wanted competence and communication from carers. South Asian people frequently discussed needing care from someone with a shared language, but language differences could also be an issue for White British people. Some clinicians thought South Asian people had a stronger preference to provide care within the family. We found that preferences for who provides care varied across families regardless of ethnicity. Those with more financial resources and English language have more options for care that meets their needs. CONCLUSIONS: People of the same background make differing choices about care. Equitable access to care is impacted by people's personal resources, and people from South Asian backgrounds may experience the double disadvantage of having fewer options for care that meets their needs and fewer resources to seek care elsewhere.

A qualitative exploration of older people's lived experiences of homelessness and memory problems - stakeholder perspectives.

BACKGROUND: The numbers of older people experiencing both homelessness and memory problems are growing, yet their complex health, housing and care needs remain undelineated and unmet. There is a critical gap in understanding what can improve the care, support and experiences of this group. In this qualitative study we explore how stakeholders understand memory problems among older people in the context of homelessness and consider what they judge gets in the way of achieving positive outcomes. METHOD: We conducted reflexive thematic analysis of qualitative interviews (n = 49) using a semi-structured topic guide, with 17 older people (aged ≥ 50 years) experiencing memory problems and homelessness, 15 hostel staff and managers, and 17 health, housing and social care practitioners. We recruited participants from six homelessness hostels, one specialist care home and National Health and Local Authority Services in England. RESULTS: We identified four overarching themes. The population is not taken seriously; multiple causes are hard to disentangle; risk of exploitation and vulnerability; and (dis)connection and social isolation. The transience and lack of stability associated with homelessness intensified the disorienting nature of memory and cognitive impairment, and those providing direct and indirect support required flexibility and persistence, with staff moving beyond traditional roles to advocate, provide care and safeguard individuals. Memory problems were perceived by frontline staff and older people to be overlooked, misinterpreted, and misattributed as being caused by alcohol use, resulting in pervasive barriers to achieving positive and desired outcomes. CONCLUSIONS: Efforts to meet the needs of older people living with memory problems and experiencing homelessness and future interventions must reflect the complexity of their lives, often in the context of long-term alcohol use and current service provision and we make suggestions as to what could be done to improve the situation.

Incidence, age at diagnosis and survival with dementia across ethnic groups in England: A longitudinal study using electronic health records.

INTRODUCTION: We investigated the incidence of diagnosed dementia and whether age at diagnosis and survival afterward differs among the United Kingdom's three largest ethnic groups. METHODS: We used primary care electronic health records, linked Hospital Episode Statistics and mortality data for adults aged ≥65 years. We compared recorded dementia incidence 1997-2018, age at diagnosis, survival time and age at death after diagnosis in White, South Asian, and Black people. RESULTS: Dementia incidence was higher in Black people (incidence rate ratios [IRR] 1.22, 95% CI 1.15-1.30). South Asian and Black people with dementia had a younger age of death than White participants (mean difference for South Asian participants -2.97 years, (95% CI -3.41 to -2.53); and Black participants -2.66 years, (95% CI -3.08 to -2.24). DISCUSSION: South Asian and Black peoples' younger age of diagnosis and death means targeted prevention and care strategies for these groups should be prioritized and tailored to facilitate take-up.

Risk factors for dementia in Brazil: Differences by region and race.

INTRODUCTION: Twelve risk factors (RFs) account for 40% of dementia cases worldwide. However, most data for population attributable fractions (PAFs) are from high-income countries (HIC). We estimated how much these RFs account for dementia cases in Brazil, stratifying estimates by race and socioeconomic level. METHODS: We calculated the prevalence and communalities of 12 RFs using 9412 Brazilian Longitudinal Study of Aging participants, then stratified according to self-reported race and country macro-regions. RESULTS: The overall weighted PAF was 48.2%. Less education had the largest PAF (7.7%), followed by hypertension (7.6%), and hearing loss (6.8%). PAF was 49.0% and 54.0% in the richest and poorest regions, respectively. PAFs were similar among White and Black individuals (47.8% and 47.2%, respectively) but the importance of the main RF varied by race. DISCUSSION: Brazil's potential for dementia prevention is higher than in HIC. Education, hypertension, and hearing loss should be priority targets.

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.

Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Agitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia. METHODS: This parallel-group, double-blind, placebo-controlled trial-the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)-was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897. FINDINGS: Between Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference -1·74, 95% CI -7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065). INTERPRETATION: This trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Cost-effectiveness of mirtazapine for agitated behaviors in dementia: findings from a randomized controlled trial.

OBJECTIVES: To examine the costs and cost-effectiveness of mirtazapine compared to placebo over 12-week follow-up. DESIGN: Economic evaluation in a double-blind randomized controlled trial of mirtazapine vs. placebo. SETTING: Community settings and care homes in 26 UK centers. PARTICIPANTS: People with probable or possible Alzheimer's disease and agitation. MEASUREMENTS: Primary outcome included incremental cost of participants' health and social care per 6-point difference in CMAI score at 12 weeks. Secondary cost-utility analyses examined participants' and unpaid carers' gain in quality-adjusted life years (derived from EQ-5D-5L, DEMQOL-Proxy-U, and DEMQOL-U) from the health and social care and societal perspectives. RESULTS: One hundred and two participants were allocated to each group; 81 mirtazapine and 90 placebo participants completed a 12-week assessment (87 and 95, respectively, completed a 6-week assessment). Mirtazapine and placebo groups did not differ on mean CMAI scores or health and social care costs over the study period, before or after adjustment for center and living arrangement (independent living/care home). On the primary outcome, neither mirtazapine nor placebo could be considered a cost-effective strategy with a high level of confidence. Groups did not differ in terms of participant self- or proxy-rated or carer self-rated quality of life scores, health and social care or societal costs, before or after adjustment. CONCLUSIONS: On cost-effectiveness grounds, the use of mirtazapine cannot be recommended for agitated behaviors in people living with dementia. Effective and cost-effective medications for agitation in dementia remain to be identified in cases where non-pharmacological strategies for managing agitation have been unsuccessful.

What constitutes 'good' home care for people with dementia? An investigation of the views of home care service recipients and providers.

BACKGROUND: Our objective was to explore what people receiving and providing care consider to be 'good' in-home care for people living with dementia. METHODS: We conducted 36 in-depth interviews and two focus groups with key stakeholders in Australia in the first quarter of 2018. Participants included those receiving care (4 people living with dementia, 15 family carers) or providing care (9 case managers, 5 service managers, 10 home care workers). Qualitative thematic analysis was guided by Braun and Clarke's six-step approach. RESULTS: Consensus was reached across all groups on five themes considered as important for good in-home dementia care: 1) Home care workers' understanding of dementia and its impact; 2) Home care workers' demonstrating person-centred care and empathy in their care relationship with their client; 3) Good relationships and communication between care worker, person with dementia and family carers; 4) Home care workers' knowing positive practical strategies for changed behaviours; 5) Effective workplace policies and workforce culture. The results contributed to the co-design of a dementia specific training program for home care workers. CONCLUSIONS: It is crucial to consider the views and opinions of each stakeholder group involved in providing/receiving dementia care from home care workers, to inform workforce training, education program design and service design. Results can be used to inform and empower home care providers, policy, and related decision makers to guide the delivery of improved home care services. TRIAL REGISTRATION: ACTRN 12619000251123 .

Plasma proteins, cognitive decline, and 20-year risk of dementia in the Whitehall II and Atherosclerosis Risk in Communities studies.

INTRODUCTION: Plasma proteins affect biological processes and are common drug targets but their role in the development of Alzheimer's disease and related dementias remains unclear. We examined associations between 4953 plasma proteins and cognitive decline and risk of dementia in two cohort studies with 20-year follow-ups. METHODS: In the Whitehall II prospective cohort study proteins were measured using SOMAscan technology. Cognitive performance was tested five times over 20 years. Linkage to electronic health records identified incident dementia. The results were replicated in the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: Fifteen non-amyloid/non-tau-related proteins were associated with cognitive decline and dementia, were consistently identified in both cohorts, and were not explained by known dementia risk factors. Levels of six of the proteins are modifiable by currently approved medications for other conditions. DISCUSSION: This study identified several plasma proteins in dementia-free people that are associated with long-term risk of cognitive decline and dementia.