Dementia prevention, intervention, and care

Background and Purpose—This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment ...

Vascular Contributions to Cognitive Impairment and Dementia A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

A rating scale for drug-induced akathisia has been derived that incorporates diagnostic criteria for pseudoakathisia, and mild, moderate, and severe akathisia. It comprises items for rating the observable, restless movements which characterise the condition, the subjective awareness of restlessness, and any distress associated with the akathisia. In addition, there is an item for rating global severity. A standard examination procedure is recommended. The inter-rater reliability for the scale items (Cohen's kappa) ranged from 0.738 to 0.955. Akathisia was found in eight of 42 schizophrenic in-patients, and nine had pseudoakathisia, where the typical sense of inner restlessness was not reported.

A rating scale for drug-induced akathisia

https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2051-5545.2011.tb00014.x

Physical illness in patients with severe mental disorders.I. Prevalence, impact of medications and disparities in health care

An estimated 24 million people worldwide have dementia, the majority of whom are thought to have Alzheimer's disease. Thus, Alzheimer's disease represents a major public health concern and has been identified as a research priority. Although there are licensed treatments that can alleviate symptoms of Alzheimer's disease, there is a pressing need to improve our understanding of pathogenesis to enable development of disease-modifying treatments. Methods for improving diagnosis are also moving forward, but a better consensus is needed for development of a panel of biological and neuroimaging biomarkers that support clinical diagnosis. There is now strong evidence of potential risk and protective factors for Alzheimer's disease, dementia, and cognitive decline, but further work is needed to understand these better and to establish whether interventions can substantially lower these risks. In this Seminar, we provide an overview of recent evidence regarding the epidemiology, pathogenesis, diagnosis, and treatment of Alzheimer's disease, and discuss potential ways to reduce the risk of developing the disease.

SeminarAlzheimer's disease

Background
Memantine, a low affinity antagonist to glutamate NMDA receptors, may prevent excitatory neurotoxicity in dementia.

Objectives
To determine efficacy and safety of memantine for people with Alzheimer's disease (AD), vascular (VD) and mixed dementia.

Search methods
The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group was searched on 8 February 2006. This register contains references from all major healthcare databases and many ongoing trial databases and is updated regularly. In addition, the search engines Copernic and Google were used to identify unpublished trials through inspection of the websites of licensing bodies like the FDA , EMEA and NICE and of companies' websites (Lundbeck, Merz, Forest, Suntori etc) and clinical trials registries.

Selection criteria
Double-blind, parallel group, placebo-controlled, randomized trials of memantine in people with dementia.

Data collection and analysis
Data were pooled where possible. Intention-to-treat (ITT) and observed case (OC) analyses are reported.

Main results
1. Moderate to severe AD. Two out of three six month studies show a small beneficial effect of memantine. Pooled data indicate a beneficial effect at six months on cognition (2.97 points on the 100 point SIB, 95% CI 1.68 to 4.26, P < 0.00001), activities of daily living (1.27 points on the 54 point ADCS-ADLsev, 95% CI 0.44 to 2.09, P = 0.003) and behaviour (2.76 points on the 144 point NPI, 95% CI 0.88 to 4.63, P=0.004), supported by clinical impression of change (0.28 points on the 7 point CIBIC+, 95% CI 0.15 to 0.41, P < 0.0001). 
2. Mild to moderate AD. Pooled data from three unpublished studies indicate a marginal benefical effect at six months on ITT cognition (0.99 points on the 70 point ADAS-Cog, 95% CI 0.21 to 1.78, P = 0.01) which was barely detectable clinically (0.13 CIBIC+ points, 95% CI 0.01 to 0.25, P = 0.03) but no effect on behaviour, activities of daily living or OC analysis of cognition. 
3. Mild to moderate vascular dementia. Pooled data from two six month studies indicated a small beneficial effect of memantine on cognition (1.85 ADAS-Cog points, 95% CI 0.88 to 2.83, P = 0.0002), and behaviour (0.84 95% CI 0.06 to 0.91, P = 0.03) but this was not supported by clinical global measures. 
4. Patients taking memantine were slightly less likely to develop agitation (134/1739, 7.7% versus 175/1873, 9.3% OR 0.78, 95% CI 0.61 to 0.99, P = 0.04). This effect was slightly larger, but still small, in moderate to severe AD (58/506 [12%] vs 88/499 [18%]; OR = 0.6, 95% CI 0.42 to 0.86, P = 0.005). There is no evidence either way about whether it has an effect on agitation which is already present. 
5. Memantine is well tolerated.

Authors' conclusions
Memantine has a small beneficial effect at six months in moderate to severe AD. In patients with mild to moderate dementia, the small beneficial effect on cognition was not clinically detectable in those with vascular dementia and was detectable in those with AD. Memantine is well tolerated.

Memantine for dementia

Background

The World Health Organization (WHO) recommends treating all school children at regular intervals with deworming drugs in areas where helminth infection is common. The WHO state this will improve nutritional status, haemoglobin, and cognition and thus will improve health, intellect, and school attendance. Consequently, it is claimed that school performance will improve, child mortality will decline, and economic productivity will increase. Given the important health and societal benefits attributed to this intervention, we sought to determine whether they are based on reliable evidence.

Objectives

To summarize the effects of giving deworming drugs to children to treat soil-transmitted intestinal worms (nematode geohelminths) on weight, haemoglobin, and cognition; and the evidence of impact on physical well being, school attendance, school performance, and mortality.

Search methods

In February 2012, we searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, EMBASE, LILACS, mRCT, and reference lists, and registers of ongoing and completed trials.

Selection criteria

We selected randomized controlled trials (RCTs) and quasi-RCTs comparing deworming drugs for geohelminth worms with placebo or no treatment in children aged 16 years or less, reporting on weight, haemoglobin, and formal test of intellectual development. In cluster-RCTs treating communities or schools, we also sought data on school attendance, school performance, and mortality. We included trials that included health education with deworming.

Data collection and analysis

At least two authors independently assessed the trials, evaluated risk of bias, and extracted data. Continuous data were analysed using the mean difference (MD) with 95% confidence intervals (CI). Where data were missing, we contacted trial authors. We used GRADE to assess evidence quality, and this is reflected in the wording we used: high quality ("deworming improves...."); moderate quality ("deworming probably improves..."); low quality ("deworming may improve...."); and very low quality ("we don't know if deworming improves....").

Main results

We identified 42 trials, including eight cluster trials, that met the inclusion criteria. Excluding one trial where data are awaited, the 41 trials include 65,168 participants.

Screening then treating

For children known to be infected with worms (by screening), a single dose of deworming drugs may increase weight (0.58 kg, 95% CI 0.40 to 0.76, three trials, 139 participants; low quality evidence) and may increase haemoglobin (0.37 g/dL, 95% CI 0.1 to 0.64, two trials, 108 participants; low quality evidence), but we do not know if there is an effect on cognitive functioning (two trials, very low quality evidence).

Single dose deworming for all children

In trials treating all children, a single dose of deworming drugs gave mixed effects on weight, with no effects evident in seven trials, but large effects in two (nine trials, 3058 participants, very low quality evidence). The two trials with a positive effect were from the same very high prevalence setting and may not be easily generalised elsewhere. Single dose deworming probably made little or no effect on haemoglobin (mean difference (MD) 0.06 g/dL, 95% CI -0.06 to 0.17, three trials, 1005 participants; moderate evidence), and may have little or no effect on cognition (two trials, low quality evidence).

Mulitple dose deworming for all children

Over the first year of follow up, multiple doses of deworming drugs given to all children may have little or no effect on weight (MD 0.06 kg, 95% CI -0.17 to 0.30; seven trials, 2460 participants; low quality evidence); haemoglobin, (mean 0.01 g/dL lower; 95% CI 0.14 lower to 0.13 higher; four trials, 807 participants; low quality evidence); cognition (three trials, 30,571 participants, low quality evidence); or school attendance (4% higher attendance; 95% CI -6 to 14; two trials, 30,243 participants; low quality evidence);
For time periods beyond a year, there were five trials with weight measures. One cluster-RCT of 3712 children in a low prevalence area showed a large effect (average gain of 0.98 kg), whilst the other four trials did not show an effect, including a cluster-RCT of 27,995 children in a moderate prevalence area (five trials, 37,306 participants; low quality evidence). For height, we are uncertain whether there is an effect of deworming (-0.26 cm; 95% CI -0.84 to 0.31, three trials, 6652 participants; very low quality evidence). Deworming may have little or no effect on haemoglobin (0.00 g/dL, 95%CI -0.08 to 0.08, two trials, 1365 participants, low quality evidence); cognition (two trials, 3720 participants; moderate quality evidence). For school attendance, we are uncertain if there is an effect (mean attendance 5% higher, 95% CI -0.5 to 10.5, approximately 20,000 participants, very low quality evidence).
Stratified analysis to seek subgroup effects into low, medium and high helminth endemicity areas did not demonstrate any pattern of effect. In a sensitivity analysis that only included trials with adequate allocation concealment, we detected no significant effects for any primary outcomes.
One million children were randomized in a deworming trial from India with mortality as the primary outcome. This was completed in 2005 but the authors have not published the results.

Authors' conclusions

Screening children for intestinal helminths and then treating infected children appears promising, but the evidence base is small. Routine deworming drugs given to school children has been more extensively investigated, and has not shown benefit on weight in most studies, except for substantial weight changes in three trials conducted 15 years ago or more. Two of these trials were carried out in the same high prevalence setting. For haemoglobin and cognition, community deworming seems to have little or no effect, and the evidence in relation to school attendance, and school performance is generally poor, with no obvious or consistent effect. Our interpretation of this data is that it is probably misleading to justify contemporary deworming programmes based on evidence of consistent benefit on nutrition, haemoglobin, school attendance or school performance as there is simply insufficient reliable information to know whether this is so.

/pdf/deworming-drugs-for-soil-transmitted-intestinal-worms-in-35g9jg86tt.pdf

Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance

Background
Caring for someone with dementia can be emotionally and physically demanding. Respite care is any intervention designed to give rest or relief to caregivers. It is not clear what positive and negative effects such care may have on them, or on people with dementia.

Objectives
To assess the benefits and harms of respite care for people with dementia and their caregivers, in particular the effect of respite care on rates of institutionalisation.

Search methods
The trials were identified from a search of ALOIS, the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, using the terms respite* OR daycare OR caregiver* relief. ALOIS contains up-to-date records from all major healthcare databases and many ongoing trial databases.

Selection criteria
Randomised controlled trials comparing respite care with a control intervention for people with dementia.

Data collection and analysis
Two review authors carried out study selection independently and reached a consensus through discussion. Data were extracted by a single review author. The review authors contacted all investigators for methodological details not reported in the text and for additional data for three studies included in the previous version of the review.

Main results
Four trials are now included in the review, with 753 participants. They were different in many ways including the intervention, duration, outcomes and control group so pooling of data was not possible. Overall, the quality of the evidence was rated as very low. Re-analysis of outcomes using data from the published studies found no significant effects of respite care compared to no respite care on any caregiver variable. When respite care was compared to polarity therapy a significant effect was found in favour of polarity therapy for caregiver perceived stress (n = 38, MD 5.80, 95% CI 1.43 to 10.17), but not for other measures of psychological health and other caregiver outcomes. No studies reported evaluable data on outcomes related to the people with dementia.

Authors' conclusions
Current evidence does not demonstrate any benefits or adverse effects from the use of respite care for people with dementia or their caregivers. These results should be treated with caution, however, as they may reflect the lack of high quality research in this area rather than an actual lack of benefit. Given the frequency with which respite care is advocated and provided, well-designed trials are needed in this area.

Respite care for people with dementia and their carers

Background
Antipsychotic (neuroleptic) medication is used extensively to treat people with chronic mental illnesses. Its use, however, is associated with adverse effects, including movement disorders such as tardive dyskinesia (TD) – a problem often seen as repetitive involuntary movements around the mouth and face. Vitamin E has been proposed as a treatment to prevent or decrease TD.

Objectives
To determine the effects of vitamin E for people with schizophrenia or other chronic mental illnesses who also developed neuroleptic-induced TD.

Search methods
We searched the Cochrane Schizophrenia Group Trials Register (March 2010), inspected references of all identified studies for further trials and contacted authors of trials for additional information.

Selection criteria
We included reports if they were controlled trials dealing with people with neuroleptic-induced TD and schizophrenia who had been randomly allocated to either vitamin E or to a placebo or no intervention.

Data collection and analysis
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who dropped out had no improvement.

Main results
The review now includes 11 poorly reported randomised trials (total 427 people). There was no clear difference between vitamin E and placebo for the outcome of 'clinically relevant improvement in TD' (6 trials, 256 people, RR 0.95 CI 0.89 to 1.02). For the outcome of 'any improvement in TD symptoms', again, we found no clear difference between groups (7 trials, 311 people, RR 0.86 CI 0.75 to 1.00). However, people allocated to placebo showed more deterioration of their symptoms compared with those given vitamin E (5 trials, 98 people, RR 0.38 CI 0.16 to 0.9). There was no difference in the incidence of adverse effects (9 trials, 203 people, RR 1.29 CI 0.51 to 3.24) or leaving the study early (medium term 6 trials, 173 people, RR 1.29 CI 0.72 to 2.3). There is no trial-based information regarding the effect of vitamin E for those with early onset of TD.

Authors' conclusions
Small trials of limited quality suggest that vitamin E may protect against deterioration of TD. There is no evidence that vitamin E improves symptoms of this problematic and disfiguring condition once established. New and better trials are indicated in this under-researched area, and, of the many adjunctive treatments that have been given for TD, vitamin E would be a good choice for further evaluation.

/pdf/vitamin-e-for-neuroleptic-induced-tardive-dyskinesia-piqpi4s144.pdf

Vitamin E for neuroleptic-induced tardive dyskinesia.

Background
Complementary therapy has received great interest within the field of dementia treatment and the use of aromatherapy and essential oils is increasing. In a growing population where the majority of patients are treated by US Food and Drug Administration (FDA)-approved drugs, the efficacy of treatment is short term and accompanied by negative side effects. Utilisation of complimentary therapies in dementia care settings presents as one of few options that are attractive to practitioners and families as patients often have reduced insight and ability to verbally communicate adverse reactions. Amongst the most distressing features of dementia are the behavioural and psychological symptoms. Addressing this facet has received particular interest in aromatherapy trials, with a shift in focus from reducing cognitive dysfunction to the reduction of behavioural and psychological symptoms in dementia.

Objectives
To assess the efficacy of aromatherapy as an intervention for people with dementia.

Search methods
ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, was searched on 26 November 2012 and 20 January 2013 using the terms: aromatherapy, lemon, lavender, rose, aroma, alternative therapies, complementary therapies, essential oils.

Selection criteria
All relevant randomised controlled trials were considered. A minimum length of a trial and requirements for follow-up were not included, and participants in included studies had a diagnosis of dementia of any type and severity. The review considered all trials using fragrance from plants defined as aromatherapy as an intervention with people with dementia and all relevant outcomes were considered.

Data collection and analysis
Titles and abstracts extracted by the searches were screened for their eligibility for potential inclusion in the review. For Burns 2011, continuous outcomes were estimated as the mean difference between groups and its 95% confidence interval using a fixed-effect model. For Ballard 2002, analysis of co-variance was used for all outcomes, with the nursing home being treated as a random effect.

Main results
Seven studies with 428 participants were included in this review; only two of these had published usable results. Individual patient data were obtained from one trial (Ballard 2002) and additional analyses performed. The additional analyses conducted using individual patient data from Ballard 2002 revealed a statistically significant treatment effect in favour of the aromatherapy intervention on measures of agitation (n = 71, MD -11.1, 95% CI -19.9 to -2.2) and behavioural symptoms (n = 71, MD -15.8, 95% CI -24.4 to -7.2). Burns 2011, however, found no difference in agitation (n = 63, MD 0.00, 95% CI -1.36 to 1.36), behavioural symptoms (n = 63, MD 2.80, 95% CI -5.84 to 11.44), activities of daily living (n = 63, MD -0.50, 95% CI -1.79 to 0.79) and quality of life (n = 63, MD 19.00, 95% CI -23.12 to 61.12). Burns 2011 and Fu 2013 found no difference in adverse effects (n = 124, RR 0.97, 95% CI 0.15 to 6.46) when aromatherapy was compared to placebo.

Authors' conclusions
The benefits of aromatherapy for people with dementia are equivocal from the seven trials included in this review. It is important to note there were several methodological difficulties with the included studies. More well-designed, large-scale randomised controlled trials are needed before clear conclusions can be drawn regarding the effectiveness of aromatherapy for dementia. Additionally, several issues need to be addressed, such as whether different aromatherapy interventions are comparable and the possibility that outcomes may vary for different types of dementia.

Nicola Maayan

Papers

Memantine for dementia

Deworming drugs for soil-transmitted intestinal worms in children: effects on nutritional indicators, haemoglobin, and school performance

Respite care for people with dementia and their carers

Vitamin E for neuroleptic-induced tardive dyskinesia.

Aromatherapy for dementia