Sube Banerjee

Donepezil and Memantine for Moderate-to-Severe Alzheimer's Disease

BACKGROUND Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimers disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. METHODS We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimers disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS. RESULTS Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone. CONCLUSIONS In patients with moderate or severe Alzheimers disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimers Society; Current Controlled Trials number, ISRCTN49545035.).

Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial

BACKGROUND Depression is common in dementia but the evidence base for appropriate drug treatment is sparse and equivocal. We aimed to assess efficacy and safety of two of the most commonly prescribed drugs, sertraline and mirtazapine, compared with placebo. METHODS We undertook the parallel-group, double-blind, placebo-controlled, Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial in participants from old-age psychiatry services in nine centres in England. Participants were eligible if they had probable or possible Alzheimers disease, depression (lasting ≥4 weeks), and a Cornell scale for depression in dementia (CSDD) score of 8 or more. Participants were ineligible if they were clinically critical (eg, suicide risk), contraindicated to study drugs, on antidepressants, in another trial, or had no carer. The clinical trials unit at Kings College London (UK) randomly allocated participants with a computer-generated block randomisation sequence, stratified by centre, with varying block sizes, in a 1:1:1 ratio to receive sertraline (target dose 150 mg per day), mirtazapine (45 mg), or placebo (control group), all with standard care. The primary outcome was reduction in depression (CSDD score) at 13 weeks (outcomes to 39 weeks were also assessed), assessed with a mixed linear-regression model adjusted for baseline CSDD, time, and treatment centre. This study is registered, number ISRCTN88882979 and EudraCT 2006-000105-38. FINDINGS Decreases in depression scores at 13 weeks did not differ between 111 controls and 107 participants allocated to receive sertraline (mean difference 1·17, 95% CI -0·23 to 2·58; p=0·10) or mirtazapine (0·01, -1·37 to 1·38; p=0·99), or between participants in the mirtazapine and sertraline groups (1·16, -0·25 to 2·57; p=0·11); these findings persisted to 39 weeks. Fewer controls had adverse reactions (29 of 111 [26%]) than did participants in the sertraline group (46 of 107, 43%; p=0·010) or mirtazapine group (44 of 108, 41%; p=0·031), and fewer serious adverse events rated as severe (p=0·003). Five patients in every group died by week 39. INTERPRETATION Because of the absence of benefit compared with placebo and increased risk of adverse events, the present practice of use of these antidepressants, with usual care, for first-line treatment of depression in Alzheimers disease should be reconsidered. FUNDING UK National Institute of Health Research HTA Programme.

Dementia prevention, intervention, and care

Acting now on dementia prevention, intervention, and care will vastly improve living and dying for individuals with dementia and their families, and in doing so, will transform the future for society. Dementia is the greatest global challenge for health and social care in the 21st century. It occurs mainly in people older than 65 years, so increases in numbers and costs are driven, worldwide, by increased longevity resulting from the welcome reduction in people dying prematurely. The Lancet Commission on Dementia Prevention, Intervention, and Care met to consolidate the huge strides that have been made and the emerging knowledge as to what we should do to prevent and manage dementia. Globally, about 47 million people were living with dementia in 2015, and this number is projected to triple by 2050. Dementia affects the individuals with the condition, who gradually lose their abilities, as well as their relatives and other supporters, who have to cope with seeing a family member or friend become ill and decline, while responding to their needs, such as increasing dependency and changes in behaviour. Additionally, it affects the wider society because people with dementia also require health and social care. The 2015 global cost of dementia was estimated to be US

EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: I--Factors associated with carer burden.

818 billion, and this figure will continue to increase as the number of people with dementia rises. Nearly 85% of costs are related to family and social, rather than medical, care. It might be that new medical care in the future, including public health measures, could replace and possibly reduce some of this cost.

The Tourette Syndrome Diagnostic Confidence Index Development and clinical associations

The challenges presented by the increasing public health and social impact of caring for people with dementia have become clear in recent years. Previous research has identified that, while there are positive as well as negative elements to the caring role, carers are at high risk of mental health problems and that the comprehensive burden of caring has social, economic and health based elements. Co‐resident carers, especially spouses, are of primary importance in maintaining people with dementia in their own homes in the community rather than in institutional settings which may be both more costly and have greater environmental poverty. There have, however, been few studies which have sought to investigate factors associated with carer burden and differences and similarities between countries. In this study we aimed to produce a cross‐national profile of co‐resident spouse carers across the European Community, with particular attention to: living arrangements; formal and informal support; service satisfaction; perceived burden; and psychological well‐being.

Quality of life in dementia: more than just cognition. An analysis of associations with quality of life in dementia

Background: The clinical characteristics of Tourette syndrome (TS) present challenges for the systematic determination of whether individuals are affected and severity. Vocal and motor tics wax and wane, decrease over time, and may be voluntarily suppressible, and therefore may be absent at interview. Current instruments measure symptoms at interview or rate symptom severity only. Method:— To minimize error in case ascertainment and produce an instrument measuring lifetime likelihood of having had TS, clinical members of the American Tourette Syndrome Association International Genetic Collaboration developed the Diagnostic Confidence Index (DCI). The expert group worked collaboratively with progressive revision in consensus workshops using existing diagnostic criteria as guidelines. The DCI produces a score from 0 to 100 that is a measure of the likelihood of having or ever having had TS. Results: The DCI was administered to 280 consecutive patients with TS attending a TS clinic; 264 (94%) completed it, indicating high feasibility and acceptability. Its correlation with other instruments and associations with psychopathology provide support for its being a lifetime measure of TS. Conclusions: The DCI is a useful, practicable instrument in the clinic or research practice allowing an assessment of lifetime likelihood of TS. Further work is needed to test the DCI’s psychometric properties, such as its validity and reliability in populations of interest.

Randomised controlled trial of effect of intervention by psychogeriatric team on depression in frail elderly people at home

Objectives: To explore the extent to which commonly used measures of specific outcomes in dementia are an appropriate proxy for quality of life in dementia. Methods: This was a cross sectional study set in communities in London and Nottingham, comprising 101 people with dementia and their 99 main family caregivers. The main outcome measures were health related quality of life in dementia (measured by the DEMQOL-Proxy), cognition (Mini Mental State Examination), functional impairment (Barthel Index), behavioural and psychological symptoms in dementia (Neuropsychiatric Inventory; NPI), and carer mental health (General Health Questionnaire). Results: On univariate analysis, decreased quality of life was statistically significantly correlated with higher levels of behavioural and psychological disturbance (NPI total score and its agitation, depression, anxiety, disinhibition, and irritability subscales); younger age of the person with dementia; and poorer mental health of the carer. Quality of life was not statistically significantly associated with cognition or carer age. In a multivariate model, psychological and behavioural disturbance and patient age remained statistically significantly associated with quality of life. Carer mental health was no longer statistically significantly associated, and cognition and functional limitation remained statistically insignificant. Conclusions: These data suggest that quality of life in dementia is complex, and that simple proxy substitutions of discrete measures such as cognition or function are likely to miss important factors.

Development of a new measure of health-related quality of life for people with dementia: DEMQOL.

Abstract Objective: To investigate the efficacy of intervention by a psychogeriatric team in the treatment of depression in elderly disabled people receiving home care from their local authority. Design: Randomised controlled trial with blind follow up six months after recruitment. Setting: Community of south east London. Subjects: 69 people aged 65 or over who received home care and were depressed according to criteria of the standardised automatic geriatric examination for computer assisted taxonomy (AGECAT). 33 were randomly allocated to an intervention group and 36 to a control group. Intervention: Members of the intervention group received an individual package of care that was formulated by the community psychogeriatric team in their catchment area and implemented by a researcher working as a member of that team. The control group received normal general practitioner care. Main outcome measures: Recovery from depression (AGECAT case at recruitment but non-case at follow up). Results: Data were analysed on an intention to treat basis. 19 (58%) of the intervention group recovered compared with only nine (25%) of the control group, a difference of 33% (95% confidence interval 10% to 55%). This powerful treatment effect persisted after controlling for possible confounders in logistic regression analysis, with members of the intervention group more likely than members of the control group to have recovered at follow up (odds ratio 9.0 (2.0 to 41.5)). This did not seem to be a simple effect of antidepressant prescription: use of antidepressants at follow up did not have a significant effect (multiply adjusted odds ratio 0.3 (0.0 to 1.9)). Conclusions: Depression is treatable in elderly people receiving home care. Therapeutic nihilism based on an assumed poor response to treatment in these socially isolated, disabled elderly people in the community is not supported. Key messages This randomised controlled trial evaluated whether intervention by a psychi- atric team would improve depression in elderly people receiving home care Overall, 58% of those receiving the intervention had recovered from their depression six months later compared with only 25% of those receiving unsup- plemented general practitioner care These results should be achievable by other community old age psychiatry services The current comparative inaction on the part of health and social services needs to be changed

EUROCARE: a cross-national study of co-resident spouse carers for people with Alzheimer's disease: II--A qualitative analysis of the experience of caregiving.

BACKGROUND We identified the need to develop a scientifically rigorous measure of health-related quality of life (HRQL) in dementia that would be appropriate for use at all stages of dementia severity and would be available in both self- and proxy-report versions. METHOD We used standard psychometric methods to eliminate items with poor psychometric properties (item-reduction field test) and to assess the acceptability, reliability and validity of the item-reduced instruments (psychometric evaluation field test). We developed and validated two versions of DEMQOL: a 28-item interviewer-administered questionnaire that is self-reported by the person with dementia (DEMQOL) and a 31-item interviewer-administered questionnaire that is proxy-reported by a caregiver (DEMQOL-Proxy). RESULTS DEMQOL shows high reliability (internal consistency and test-retest) and moderate validity in people with mild/moderate dementia. DEMQOL-Proxy shows good acceptability and internal consistency and moderate evidence of validity in people with mild/moderate and severe dementia. Test-retest reliability and performance in people with severe dementia need further testing. CONCLUSIONS DEMQOL and DEMQOL-Proxy show psychometric properties that are comparable with the best available dementia-specific measures of HRQL. We recommend that DEMQOL and DEMQOL-Proxy are used together. Reliability and validity need to be confirmed in independent samples and responsiveness needs to be evaluated.

Community study of people who live in squalor

Spouses caring for a partner with dementia are subject to physical, psychological and social stresses. In view of the part played by spouse carers in preventing admission to institutional care, a fuller understanding of the subjective experience of caring is an important area of enquiry. Qualitative analysis of their accounts of the difficulties and rewards in looking after their partners may indicate strategies to support them and to alleviate the stresses that they experience.