Determinants of hospital readmissions in older people with dementia: a narrative review.

INTRODUCTION: Over 50% of hospitalised older people with dementia have multimorbidity, and are at an increased risk of hospital readmissions within 30 days of their discharge. Between 20-40% of these readmissions may be preventable. Current research focuses on the physical causes of hospital readmissions. However, older people with dementia have additional psychosocial factors that are likely to increase their risk of readmissions. This narrative review aimed to identify psychosocial determinants of hospital readmissions, within the context of known physical factors. METHODS: Electronic databases MEDLINE, EMBASE, CINAHL and PsychInfo were searched from inception until July 2022 and followed up in February 2024. Quantitative and qualitative studies in English including adults aged 65 years and over with dementia, their care workers and informal carers were considered if they investigated hospital readmissions. An inductive approach was adopted to map the determinants of readmissions. Identified themes were described as narrative categories. RESULTS: Seventeen studies including 7,194,878 participants met our inclusion criteria from a total of 6369 articles. Sixteen quantitative studies included observational cohort and randomised controlled trial designs, and one study was qualitative. Ten studies were based in the USA, and one study each from Taiwan, Australia, Canada, Sweden, Japan, Denmark, and The Netherlands. Large hospital and insurance records provided data on over 2 million patients in one American study. Physical determinants included reduced mobility and accumulation of long-term conditions. Psychosocial determinants included inadequate hospital discharge planning, limited interdisciplinary collaboration, socioeconomic inequalities among ethnic minorities, and behavioural and psychological symptoms. Other important psychosocial factors such as loneliness, poverty and mental well-being, were not included in the studies. CONCLUSION: Poorly defined roles and responsibilities of health and social care professionals and poor communication during care transitions, increase the risk of readmission in older people with dementia. These identified psychosocial determinants are likely to significantly contribute to readmissions. However, future research should focus on the understanding of the interaction between a host of psychosocial and physical determinants, and multidisciplinary interventions across care settings to reduce hospital readmissions.

A pragmatic, multicentre, double-blind, placebo-controlled randomised trial to assess the safety, clinical and cost-effectiveness of mirtazapine and carbamazepine in people with Alzheimer's disease and agitated behaviours: the HTA-SYMBAD trial.

Background: Agitation is common and impacts negatively on people with dementia and carers. Non-drug patient-centred care is first-line treatment, but we need other treatment when this fails. Current evidence is sparse on safer and effective alternatives to antipsychotics. Objectives: To assess clinical and cost-effectiveness and safety of mirtazapine and carbamazepine in treating agitation in dementia. Design: Pragmatic, phase III, multicentre, double-blind, superiority, randomised, placebo-controlled trial of the clinical effectiveness of mirtazapine over 12 weeks (carbamazepine arm discontinued). Setting: Twenty-six UK secondary care centres. Participants: Eligibility: probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, Cohen-Mansfield Agitation Inventory score ≥ 45. Interventions: Mirtazapine (target 45 mg), carbamazepine (target 300 mg) and placebo. Outcome measures: Primary: Cohen-Mansfield Agitation Inventory score 12 weeks post randomisation. Main economic outcome evaluation: incremental cost per six-point difference in Cohen-Mansfield Agitation Inventory score at 12 weeks, from health and social care system perspective. Data from participants and informants at baseline, 6 and 12 weeks. Long-term follow-up Cohen-Mansfield Agitation Inventory data collected by telephone from informants at 6 and 12 months. Randomisation and blinding: Participants allocated 1 : 1 : 1 ratio (to discontinuation of the carbamazepine arm, 1 : 1 thereafter) to receive placebo or carbamazepine or mirtazapine, with treatment as usual. Random allocation was block stratified by centre and residence type with random block lengths of three or six (after discontinuation of carbamazepine, two or four). Double-blind, with drug and placebo identically encapsulated. Referring clinicians, participants, trial management team and research workers who did assessments were masked to group allocation. Results: Two hundred and forty-four participants recruited and randomised (102 mirtazapine, 102 placebo, 40 carbamazepine). The carbamazepine arm was discontinued due to slow overall recruitment; carbamazepine/placebo analyses are therefore statistically underpowered and not detailed in the abstract. Mean difference placebo-mirtazapine (-1.74, 95% confidence interval -7.17 to 3.69; p = 0.53). Harms: The number of controls with adverse events (65/102, 64%) was similar to the mirtazapine group (67/102, 66%). However, there were more deaths in the mirtazapine group (n = 7) by week 16 than in the control group (n = 1). Post hoc analysis suggests this was of marginal statistical significance (p = 0.065); this difference did not persist at 6- and 12-month assessments. At 12 weeks, the costs of unpaid care by the dyadic carer were significantly higher in the mirtazapine than placebo group [difference: £1120 (95% confidence interval £56 to £2184)]. In the cost-effectiveness analyses, mean raw and adjusted outcome scores and costs of the complete cases samples showed no differences between groups. Limitations: Our study has four important potential limitations: (1) we dropped the proposed carbamazepine group; (2) the trial was not powered to investigate a mortality difference between the groups; (3) recruitment beyond February 2020, was constrained by the COVID-19 pandemic; and (4) generalisability is limited by recruitment of participants from old-age psychiatry services and care homes. Conclusions: The data suggest mirtazapine is not clinically or cost-effective (compared to placebo) for agitation in dementia. There is little reason to recommend mirtazapine for people with dementia with agitation. Future work: Effective and cost-effective management strategies for agitation in dementia are needed where non-pharmacological approaches are unsuccessful. Study registration: This trial is registered as ISRCTN17411897/NCT03031184. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 23. See the NIHR Journals Library website for further project information.

It is common for people with Alzheimer's disease to experience agitation, for example feeling restless or unsettled. If left untreated, agitation can lead to poorer quality of life and increased hospitalisation and strain for family carers. Often these symptoms are treated with medications that are usually used to manage psychosis (antipsychotic drugs), but such medication has limited effectiveness and can cause serious adverse effects to patients, including risk of increased death. Two medications that are already commonly prescribed for other health issues, mirtazapine (an antidepressant) and carbamazepine (a drug used to treat epilepsy), had been identified as a possible alternative way of treating agitation in Alzheimer's disease that might not have the harms associated with antipsychotic medication. In this study, we compared the effects of giving mirtazapine or carbamazepine with a dummy drug (placebo) in people with Alzheimer's disease who were experiencing agitation. The results of the study showed that neither medication was any more effective than the placebo in reducing agitation over 12 weeks in terms of improving symptoms, or in economic terms. Mirtazapine may lead to additional carer costs as compared to placebo. The study findings are stronger for mirtazapine than carbamazepine because the carbamazepine arm was stopped when it had recruited less than half the numbers needed. That was done because the study was not recruiting quickly enough to support both the mirtazapine and the carbamazepine arms. The findings from this study show that mirtazapine should not be recommended to treat agitation in Alzheimer's disease. More work is needed to formulate effective ways and to test new drug and non-drug treatments for agitation in dementia.

The use of the integrated cognitive assessment to improve the efficiency of primary care referrals to memory services in the accelerating dementia pathway technologies study.

Background: Current primary care cognitive assessment tools are either crude or time-consuming instruments that can only detect cognitive impairment when it is well established. This leads to unnecessary or late referrals to memory services, by which time the disease may have already progressed into more severe stages. Due to the COVID-19 pandemic, some memory services have adapted to the new environment by shifting to remote assessments of patients to meet service user demand. However, the use of remote cognitive assessments has been inconsistent, and there has been little evaluation of the outcome of such a change in clinical practice. Emerging research has highlighted computerized cognitive tests, such as the Integrated Cognitive Assessment (ICA), as the leading candidates for adoption in clinical practice. This is true both during the pandemic and in the post-COVID-19 era as part of healthcare innovation. Objectives: The Accelerating Dementias Pathways Technologies (ADePT) Study was initiated in order to address this challenge and develop a real-world evidence basis to support the adoption of ICA as an inexpensive screening tool for the detection of cognitive impairment and improving the efficiency of the dementia care pathway. Methods: Ninety-nine patients aged 55-90 who have been referred to a memory clinic by a general practitioner (GP) were recruited. Participants completed the ICA either at home or in the clinic along with medical history and usability questionnaires. The GP referral and ICA outcome were compared with the specialist diagnosis obtained at the memory clinic.Participants were given the option to carry out a retest visit where they were again given the chance to take the ICA test either remotely or face-to-face. Results: The primary outcome of the study compared GP referral with specialist diagnosis of mild cognitive impairment (MCI) and dementia. Of those the GP referred to memory clinics, 78% were necessary referrals, with ~22% unnecessary referrals, or patients who should have been referred to other services as they had disorders other than MCI/dementia. In the same population the ICA was able to correctly identify cognitive impairment in ~90% of patients, with approximately 9% of patients being false negatives. From the subset of unnecessary GP referrals, the ICA classified ~72% of those as not having cognitive impairment, suggesting that these unnecessary referrals may not have been made if the ICA was in use. ICA demonstrated a sensitivity of 93% for dementia and 83% for MCI, with a specificity of 80% for both conditions in detecting cognitive impairment. Additionally, the test-retest prediction agreement for the ICA was 87.5%. Conclusion: The results from this study demonstrate the potential of the ICA as a screening tool, which can be used to support accurate referrals from primary care settings, along with the work conducted in memory clinics and in secondary care. The ICA's sensitivity and specificity in detecting cognitive impairment in MCI surpassed the overall standard of care reported in existing literature.

Evidence of emerging BBB changes in mid-age apolipoprotein E epsilon-4 carriers.

INTRODUCTION: Studies have recognized that the loss of the blood-brain barrier (BBB) integrity is a major structural biomarker where neurodegenerative disease potentially begins. Using a combination of high-quality neuroimaging techniques, we investigated potential subtle differences in BBB permeability in mid-age healthy people, comparing carriers of the apolipoprotein E epsilon-4 (APOEε4) genotype, the biggest risk factor for late onset, non-familial AD (LOAD) with APOEε3 carriers, the population norm. METHODS: Forty-one cognitively healthy mid-age participants (42-59) were genotyped and pseudo-randomly selected to participate in the study by a third party. Blind to genotype, all participants had a structural brain scan acquisition including gadolinium-based dynamic contrast-enhanced magnetic resonance imaging acquired using a T1-weighted 3D vibe sequence. A B1 map and T1 map were acquired as part of the multi-parametric mapping acquisition. RESULTS: Non-significant, but subtle differences in blood-brain barrier permeability were identified between healthy mid-age APOEε4 and APOEε3 carriers, matched on age, education, and gender. DISCUSSION: This study demonstrated a tendency toward BBB permeability in APOEε4 participants emerging from mid-age, with quantitative differences observable on a number of the measures. While the differences did not reach a statistical significance, the results from this study hint at early changes in ε4 carrier BBB that may help identify at-risk populations and facilitate the development of early interventions to change the trajectory of decline.

Care home staff perceptions of implementing a quality of life instrument into routine care practice: A qualitative study.

Quality of life is an important outcome in older-adult care. Measuring resident quality of life may offer ways to improve it and to improve quality of care. However, in the UK quality of life is rarely measured as a part of routine care. Our study aimed to understand the views of care home staff about using a quality of life instrument as a part of routine care in order to support its implementation into routine practice. In a qualitative study, we conducted 35 interviews with care home staff and two focus groups with four care home managers from three care homes in East Sussex, England. Data were collected between September 2015 and February 2016. Care staff and managers were aged on average 40 (SD = 12.2) and 43.7 (SD = 14.4) years and had worked in the care sector an average of 11.4 (SD = 10.2) and 23.7 (SD = 14.1) years, respectively. Participants were predominantly female and white British. Interviews and focus groups were analysed using thematic analysis. Findings identified two overarching themes of 'Perceived gains' and 'Implementation'. Overall, there was a lot of positivity towards using a quality of life instrument in routine practice. This positivity was an important feature in how the instrument was perceived as fitting into practice. Participants identified several barriers and discussed how to overcome them. Results from the study demonstrate that routine measurement of quality of life is positively received by care staff. They believed that measuring quality of life as a part of care practice could lead to improvements in resident quality of life, staff knowledge and understanding and care practices. The findings suggest that routinely measuring quality of life as a part of normal care could also have more far-reaching effects on the provision of person-centred care provided by care staff.

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.

Night-to-night variation in sleep associates with day-to-day variation in vigilance, cognition, memory, and behavioral problems in Alzheimer's disease.

Introduction: Sleep disturbances are commonly reported in people living with Alzheimer's disease (AD), but it is currently unknown whether night-to-night variation in sleep predicts day-to-day variation in vigilance, cognition, mood, and behavior (daytime measures). Methods: Subjective and objective sleep and daytime measures were collected daily for 2 weeks in 15 participants with mild AD, eight participants with mild cognitive impairment (MCI), and 22 participants with no cognitive impairment (NCI). Associations between daytime measures and four principal components of sleep (duration, quality, continuity, and latency) were quantified using mixed-model regression. Results: Sleepiness, alertness, contentedness, everyday memory errors, serial subtraction, and behavioral problems were predicted by at least one of the components of sleep, and in particular sleep duration and continuity. Associations between variations in sleep and daytime measures were linear or quadratic and often different between participants with AD and those with NCI. Discussion: These findings imply that daytime functioning in people with AD may be improved by interventions that target sleep continuity.

What factors have influenced quality of life in people with dementia and their family carers during the COVID-19 pandemic: a qualitative study.

OBJECTIVES: The COVID-19 pandemic has led to significant disruption to health and social care services. For people with dementia and their family carers this is problematic, as a group who rely on timely and responsive services to live well with the condition. This study has sought to understand how COVID-19 has affected the quality of life of people diagnosed with dementia and their family carers. DESIGN: Our mixed-methods study was nested in a larger cohort study of an education programme, Time for Dementia. SETTING: The study took place in the South-East of England. PARTICIPANTS: Existing study participants, family carers were approached about the COVID-19 nested study. A purposeful sample of participants were invited to take part in in-depth qualitative interview. The sample included family carers in a range of different caring situations. MEASUREMENT: Interviews were undertaken remotely by telephone. Interviews sought to understand quality of life before the pandemic, impact of the restrictions on both the person with dementia and family carer, role of services and other agencies as well as supportive factors. Data were analysed using thematic analysis. RESULTS: 16 family carers were interviewed. Seven themes were identified from our analysis: (1) decreased social interaction; (2) reduced support; (3) deteriorating cognitive and physical health for the person with dementia; (4) decreased carer well-being; (5) difficulties understanding COVID-19 restrictions; (6) limited impact for some and (7) trust and relationship with care home. There was little change between themes during the first and second wave of national lockdowns. CONCLUSIONS: Our study provides an understanding the short-term impact of COVID-19 on the quality of life of people with dementia and their family carers. Our findings suggest that recovery between the first and second wave of the restrictions did not automatically take place.

Covid-19 and the quality of life of people with dementia and their carers-The TFD-C19 study.

INTRODUCTION: COVID-19 has placed unprecedented pressure on dementia health and social care systems worldwide. This has resulted in reduced services and support for people with dementia and their family carers. There are gaps in the evidence on the impact of the pandemic on Quality of Life (QoL). We carried out a study on the impact of the pandemic on the QoL of a group of people with dementia and their family carers who were part of a larger existing cohort study. METHODS: We quantitatively measured QoL, on two occasions during the two national lockdowns in 2020 and compared these data with those obtained when they entered the study (before the pandemic). Measures used included: DEMQOL-Proxy, Clinical Dementia Rating Scale and C-DEMQOL. To understand how QoL changed over time, a repeated measures ANOVA was run for each dependent variable with the following variables entered as co-variates: duration in study, baseline dementia severity, gender of the family carer, gender of the person with dementia, family carer relationship, dementia type, living status, age of the person with dementia, and age of the family carer. RESULTS: 248 participants took part in the study. QoL scores did not significantly decline between either time period for the person with dementia or their family carer. There was variation in subgroups; with co-resident status, carer relationship, gender of the person with dementia, age of the person with dementia, and baseline cognitive status influencing QoL outcomes in family carers. DISCUSSION: It is striking that people with dementia and their carers did not report a decline in QoL during the pandemic or in the months following restrictions suggesting the possibility of resilience. Variation in subgroups suggests that specific groups of family carers were more vulnerable to lower QoL; indicating the need for more tailored, nuanced support during this period.

The Use of a Computerized Cognitive Assessment to Improve the Efficiency of Primary Care Referrals to Memory Services: Protocol for the Accelerating Dementia Pathway Technologies (ADePT) Study.

BACKGROUND: Existing primary care cognitive assessment tools are crude or time-consuming screening instruments which can only detect cognitive impairment when it is well established. Due to the COVID-19 pandemic, memory services have adapted to the new environment by moving to remote patient assessments to continue meeting service user demand. However, the remote use of cognitive assessments has been variable while there has been scant evaluation of the outcome of such a change in clinical practice. Emerging research in remote memory clinics has highlighted computerized cognitive tests, such as the Integrated Cognitive Assessment (ICA), as prominent candidates for adoption in clinical practice both during the pandemic and for post-COVID-19 implementation as part of health care innovation. OBJECTIVE: The aim of the Accelerating Dementia Pathway Technologies (ADePT) study is to develop a real-world evidence basis to support the adoption of ICA as an inexpensive screening tool for the detection of cognitive impairment to improve the efficiency of the dementia care pathway. METHODS: Patients who have been referred to a memory clinic by a general practitioner (GP) are recruited. Participants complete the ICA either at home or in the clinic along with medical history and usability questionnaires. The GP referral and ICA outcome are compared with the specialist diagnosis obtained at the memory clinic. The clinical outcomes as well as National Health Service reference costing data will be used to assess the potential health and economic benefits of the use of the ICA in the dementia diagnosis pathway. RESULTS: The ADePT study was funded in January 2020 by Innovate UK (Project Number 105837). As of September 2021, 86 participants have been recruited in the study, with 23 participants also completing a retest visit. Initially, the study was designed for in-person visits at the memory clinic; however, in light of the COVID-19 pandemic, the study was amended to allow remote as well as face-to-face visits. The study was also expanded from a single site to 4 sites in the United Kingdom. We expect results to be published by the second quarter of 2022. CONCLUSIONS: The ADePT study aims to improve the efficiency of the dementia care pathway at its very beginning and supports systems integration at the intersection between primary and secondary care. The introduction of a standardized, self-administered, digital assessment tool for the timely detection of neurodegeneration as part of a decision support system that can signpost accordingly can reduce unnecessary referrals, service backlog, and assessment variability. TRIAL REGISTRATION: ISRCTN 16596456; https://www.isrctn.com/ISRCTN16596456. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/34475.

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.

Bilingualism: A Global Public Health Strategy for Healthy Cognitive Aging.

Dementia is a global public health priority which cost global societies $818 billion in 2015 and is disproportionately impacting low and middle-income countries (LMICs). With limited availability of disease modifying drugs to treat Alzheimer's disease (AD), researchers have increasingly focused on preventative strategies which may promote healthy cognitive aging and mitigate the risk of cognitive impairment in aging. Lifelong bilingualism has been presented as both a highly debated and promising cognitive reserve factor which has been associated with better cognitive outcomes in aging. A recent metanalysis has suggested that bilingual individuals present on average 4.05 years later with the clinical features of AD than monolinguals. Bilinguals are also diagnosed with AD ~2.0 years later than monolingual counterparts. In this perspective piece we critically evaluate the findings of this metanalysis and consider the specific implications of these findings to LMICs. Furthermore, we appraise the major epidemiological studies conducted globally on bilingualism and the onset of dementia. We consider how both impactful and robust studies of bilingualism and cognition in older age may be conducted in LMICs. Given the limited expenditure and resources available in LMICs and minimal successes of clinical trials of disease modifying drugs we propose that bilingualism should be positioned as an important and specific public health strategy for maintaining healthy cognitive aging in LMICs. Finally, we reflect upon the scope of implementing bilingualism within the education systems of LMICs and the promotion of bilingualism as a healthy cognitive aging initiative within government policy.

Psychometric properties and feasibility of use of dementia specific quality of life instruments for use in care settings: a systematic review.

BACKGROUND: Over 400,000 people live in care home settings in the UK. One way of understanding and improving the quality of care provided is by measuring and understanding the quality of life (QoL) of those living in care homes. This review aimed to identify and examine the psychometric properties including feasibility of use of dementia-specific QoL measures developed or validated for use in care settings. DESIGN: Systematic review. METHODS: Instruments were identified using four electronic databases (PubMed, PsycINFO, Web of Science, and CINAHL) and lateral search techniques. Searches were conducted in January 2017. Studies which reported on the development and/or validation of dementia specific QoL instruments for use in care settings written in English were eligible for inclusion. The methodological quality of the studies was assessed using the COSMIN checklist. Feasibility was assessed using a checklist developed specifically for the review. RESULTS: Six hundred and sixteen articles were identified in the initial search. After de-duplication, screening and further lateral searches were performed, 25 studies reporting on 9 dementia-specific QoL instruments for use in care home settings were included in the review. Limited evidence was available on the psychometric properties of many instruments identified. Higher-quality instruments were not easily accessible or had low feasibility of use. CONCLUSIONS: Few high-quality instruments of QoL validated for use in care home settings are readily or freely available. This review highlights the need to develop a well-validated measure of QoL for use within care homes that is also feasible and accessible.

Mid age APOE ε4 carriers show memory-related functional differences and disrupted structure-function relationships in hippocampal regions.

Carriers of the APOE e4 allele are at higher risk of age-related cognitive decline and Alzheimer's disease (AD). The underlying neural mechanisms are uncertain, but genotype differences in medial temporal lobe (MTL) functional activity and structure at mid-age might contribute. We tested 16 non-e4 and 16 e4 carriers (aged 45-55) on a subsequent memory task in conjunction with MRI to assess how hippocampal volume (from T1 structural) and microstructure (neurite orientation-dispersion, from NODDI) differs by genotype and in relation to memory encoding. No previous study has investigated APOE effects on hippocampal microstructure using NODDI. Recall performance did not differ by genotype. A genotype by condition interaction in left parahippocampus indicated that in e4 carriers activity did not differentiate subsequently remembered from forgotten words. Hippocampal volumes and microstructure also did not differ by genotype but hippocampal volumes correlated positively with recognition performance in non-e4 carriers only. Similarly, greater hippocampal neurite orientation-dispersion was linked to better recall but only in non-e4s. Thus, we suggest that mid-age e4 carriers show a breakdown of normal MTL activation and structure-performance relationships. This could reflect an inability to utilise compensatory mechanisms, and contribute to higher risk of cognitive decline and AD in later life.

Prospective Memory: Age related change is influenced by APOE genotype.

Non-focal prospective memory (PM) is sensitive to age-related decline; an additional impairment in focal PM is characteristic of mild stage Alzheimer's disease. This research explored whether, by mid-adulthood, the distinct demands of focal and non-focal PM expose differences in carriers of an APOE ε4 allele, a genetic risk factor for Alzheimer's disease. Thirty-three young and 55 mid-age adults, differentiated by APOE genotype, completed a category-decision task with a concurrent focal or non-focal PM demand. Only mid-age ε4 carriers showed a cost of carrying a focal PM intention. In addition, mid-age ε4 carriers showed a significantly greater cost of carrying a non-focal PM intention than young ε4 carriers, supporting a profile of accelerated aging. Consistency in the profile of cost differences observed in mid-age ε4 carriers and pathological aging may indicate premature vulnerability. Future research correlating a shift in PM performance with early genotype differences in brain-based markers of decline is important.

Are symptoms of insomnia in primary care associated with subsequent onset of dementia? A matched retrospective case-control study.

Objective: There is evidence from neuroimaging studies of an association between insomnia and early dementia biomarkers, but observational studies have so far failed to show a clear association between insomnia and the later development of dementia. We investigated the association between dementia diagnosis and recording of insomnia symptoms 5-10 years earlier in primary care.Method: A case-control study using data from the Clinical Practice Research Datalink. 15,209 cases with dementia (either Alzheimer's, vascular, mixed or non-specific subtypes) at least 65 years old at time of diagnosis, were matched with the same number of controls on year of birth and gender. We ascertained the presence of insomnia symptoms during a five-year period starting 10 years before the index date. Odds ratios for developing dementia were estimated using logistic regression after controlling for hypnotic exposure and physical and mental health comorbidities.Results: The adjusted odds ratio for dementia in those with previous insomnia was 1.34 (95% CI = 1.20-1.50).Conclusion: There is an association between dementia and previous insomnia. It may be possible to incorporate insomnia into predictive tools for dementia.

Minocycline at 2 Different Dosages vs Placebo for Patients With Mild Alzheimer Disease: A Randomized Clinical Trial.

Importance: There are no disease-modifying treatments for Alzheimer disease (AD), the most common cause of dementia. Minocycline is anti-inflammatory, protects against the toxic effects of ß-amyloid in vitro and in animal models of AD, and is a credible repurposed treatment candidate. Objective: To determine whether 24 months of minocycline treatment can modify cognitive and functional decline in patients with mild AD. Design, Setting, and Participants: Participants were recruited into a double-blind randomized clinical trial from May 23, 2014, to April 14, 2016, with 24 months of treatment and follow-up. This multicenter study in England and Scotland involved 32 National Health Service memory clinics within secondary specialist services for people with dementia. From 886 screened patients, 554 patients with a diagnosis of mild AD (Standardised Mini-Mental State Examination [sMMSE] score ≥24) were randomized. Interventions: Participants were randomly allocated 1:1:1 in a semifactorial design to receive minocycline (400 mg/d or 200 mg/d) or placebo for 24 months. Main Outcomes and Measures: Primary outcome measures were decrease in sMMSE score and Bristol Activities of Daily Living Scale (BADLS), analyzed by intention-to-treat repeated-measures regression. Results: Of 544 eligible participants (241 women and 303 men), the mean (SD) age was 74.3 (8.2) years, and the mean (SD) sMMSE score was 26.4 (1.9). Fewer participants completed 400-mg minocycline hydrochloride treatment (28.8% [53 of 184]) than 200-mg minocycline treatment (61.9% [112 of 181]) or placebo (63.7% [114 of 179]; P < .001), mainly because of gastrointestinal symptoms (42 in the 400-mg group, 15 in the 200-mg group, and 10 in the placebo group; P < .001), dermatologic adverse effects (10 in the 400-mg group, 5 in the 200-mg group, and 1 in the placebo group; P = .02), and dizziness (14 in the 400-mg group, 3 in the 200-mg group, and 1 in the placebo group; P = .01). Assessment rates were lower in the 400-mg group: 68.4% (119 of 174 expected) for sMMSE at 24 months compared with 81.8% (144 of 176) for the 200-mg group and 83.8% (140 of 167) for the placebo group. Decrease in sMMSE scores over 24 months in the combined minocycline group was similar to that in the placebo group (4.1 vs 4.3 points). The combined minocycline group had mean sMMSE scores 0.1 points higher than the placebo group (95% CI, -1.1 to 1.2; P = .90). The decrease in mean sMMSE scores was less in the 400-mg group than in the 200-mg group (3.3 vs 4.7 points; treatment effect = 1.2; 95% CI, -0.1 to 2.5; P = .08). Worsening of BADLS scores over 24 months was similar in all groups: 5.7 in the 400-mg group, 6.6 in the 200-mg group, and 6.2 in the placebo groups (treatment effect for minocycline vs placebo = -0.53; 95% CI, -2.4 to 1.3; P = .57; treatment effect for 400 mg vs 200 mg of minocycline = -0.31; 95% CI, -0.2 to 1.8; P = .77). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data. Conclusions and Relevance: Minocycline did not delay the progress of cognitive or functional impairment in people with mild AD during a 2-year period. This study also found that 400 mg of minocycline is poorly tolerated in this population. Trial Registration: isrctn.org Identifier: ISRCTN16105064.

Cambridge Cognitive Examination and Hachinski Ischemic Score as predictors of MRI confirmed pathology in dementia: A cross-sectional study.

AIMS AND BACKGROUND: Dementia is diagnosed through a combination of clinical assessment, cognitive assessment tools and neuroimaging. The aim of this retrospective, naturalistic study was to explore the association between the clinical assessment tools used in a memory clinic and the findings of Magnetic Resonance Imaging (MRI) scans in patients with dementia. METHODS: Data were collected through routine clinical practice for all patients assessed at a memory assessment clinic in East Sussex, UK. Included patients had an MRI scan and received a formal diagnosis of dementia. Multinomial logistic regression was used to investigate the associations between atrophy on MRI with age, gender, Cambridge Cognitive Examination (CAMCOG) and Hachinski Ischemic Score (HIS). Ordinal logistic regression was used to study the associations between vascular findings on MRI with age, gender, CAMCOG and HIS. Because of the distribution of HIS scores a cut-off of 1 or greater was used in the regression analysis. RESULTS: Male gender was associated with an increased likelihood of moderate atrophy (relative risk ratio (RRR) = 1.99, 95% confidence interval (CI) = 1.04-3.82), severe atrophy (RRR = 3.04, 95% CI = 1.38-6.68) and regional atrophy (RRR = 2.25, 95% CI = 1.26-4.00) on MRI. An increase of one point on the CAMCOG was associated with a decreased risk of regional atrophy (RRR = 0.98, 95% CI = 0.96-1.00) on MRI. There were no significant associations between age, or HIS, and atrophy on MRI. An increase in age of one year was associated with an increase in severity of vascular pathology reported on MRI (OR = 1.08, 95% CI = 1.05-1.12). Male gender was associated with reduced severity of vascular pathology reported on MRI (OR = 0.53, 95% CI = 0.36-0.78). There were no associations between CAMCOG, or HIS, and vascular pathology on MRI. DISCUSSION: Our data show that CAMCOG was associated with MRI findings of regional atrophy and vascular pathology was greater in older patients. We highlight the importance of using a multi-modal approach to dementia diagnosis.

Adaptation of the DEMQOL-Proxy for routine use in care homes: a cross-sectional study of the reliability and validity of DEMQOL-CH.

OBJECTIVE: To investigate the routine use of a measure of quality of life (QoL) in care homes and assess its psychometric properties when used by care staff. DESIGN: A cross-sectional two-phase study. SETTING AND PARTICIPANTS: Data were collected from care staff in seven care homes in East Sussex, England. METHOD: Phase I: The ability of care staff from two care homes to use the DEMQOL-Proxy without interviewer administration was assessed using agreement analysis between a self-administered and interviewer-administered version of the instrument. Based on these findings, DEMQOL-Proxy was adapted into a new version, DEMQOL-CH, for use as a self-administered instrument in care homes. We assessed agreement between the new DEMQOL-CH and DEMQOL-Proxy to ensure DEMQOL-CH was used correctly. Phase II: A preliminary assessment of the psychometric properties of DEMQOL-CH when used routinely was completed in a further five care homes. RESULTS: Phase I: Nineteen care staff from two care homes completed QoL measurements for residents. Systematic error was identified when staff self-completed the DEMQOL-Proxy without an interviewer. We modified the DEMOoL-Proxy to create DEMQOL-CH; this reduced the error, producing a version that could be used more accurately by care staff. Phase II: Eleven care staff from five care homes rated resident QoL routinely. DEMQOL-CH showed acceptable psychometric properties with satisfactory reliability and validity and a clear factor structure. CONCLUSIONS: The research presents positive preliminary data on the acceptability, feasibility and performance of routine QoL measurement in care homes using an adapted version of DEMQOL-Proxy, the DEMQOL-CH. Results provide evidence to support the concept that routine measurement of QoL may be possible in care homes. Research is needed to refine and test the methodology and instrument further and to explore the potential for benefits to residents, staff and care homes in larger and more representative populations.

Social networks and loneliness in people with Alzheimer's dementia.

OBJECTIVES: Modifiable lifestyle risk factors are of great interest in the prevention and management of Alzheimer's disease (AD). Loneliness and social networks may influence onset of AD, but little is known about this relationship in people with AD. The current study aimed to explore the relationship between loneliness and social networks (social measures) and cognitive and psychopathology decline (AD outcomes) in people with AD. METHODS: Ninety-three participants with mild to moderate AD were recruited from memory clinics, in a cross-sectional study. Social networks (measured by the Lubben Social Network Scale-6), feelings of loneliness (measured by De Jong Loneliness Scale), cognition (measured by the Standardized Mini-Mental State Examination), and psychopathology (measured by the Neuropsychiatric Inventory) were assessed in an interview setting. Two multiple regressions with bootstrap were conducted on cognition and psychopathology as outcome variables. Family and friends subsets of social networks and loneliness were entered as predictors and age, gender, and depression as covariates. RESULTS: The friendship subset of social networks was significantly related to cognition (independent of age, gender, depression, loneliness, and family subset of social network): B = 0.284, P = 0.01. Neither loneliness nor social networks predicted psychopathology (Ps > 0.05). CONCLUSIONS: Maintaining or developing a close friendship network could be beneficial for cognition in people with AD. Alternatively, greater dementia severity may lead to fewer friends. More research on the direction of this relationship in people with AD is needed.