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Introduction There is evidence that neurofibrillary tangle (NFT) burden is associated with psychotic symptoms in Alzheimer disease (AD). However, it is not clear whether this association is direct or mediated through the increased cognitive impairment associated with NFTs. Methods We sought to determine whether the extended MAPT haplotype was associated with the worsening of delusions and hallucinations in a combined cohort of 95 patients who participated in 2 clinical trials of treatment with memantine. Results After controlling for baseline dementia severity, exposure to memantine, and antipsychotics, analysis shows that carriers of at least one H2 allele had a 5.4-fold ( P = .03) increased risk of worsening hallucinations. There was some evidence of association with worsening delusions but only in analysis by allele. Conclusion These results are the first to indicate that the H2 allele of the extended MAPT haplotype negatively affects the course of psychotic symptoms in AD independently of disease severity. It will be important for future research to examine MAPT transcription in people with AD with and without psychotic symptoms to understand the exact mechanisms underlying these findings. [ABSTRACT FROM AUTHOR]

The article presents a study that calculated the specific attributable risk of key adverse events associated with risperidone in people with Alzheimer's disease. The study reveals the lack of evidence of the benefit of antipsychotics to treat agitation and aggression in people with dementia, the potential harms of antipsychotic use including increased cerebrovascular events, and the alternative treatments offered including analgesia and non-drug based approaches. INSET: Non-drug treatments for use as first line approaches....

Neuropsychiatric symptoms are frequent and troublesome in people with dementia and present a major treatment challenge for clinicians. Most good practice guidelines suggest non-pharmacological treatments as the first-line therapy and there is emerging evidence, including randomized controlled trials, that a variety of psychological and training interventions, including social interaction and person-centred care training, are effective. There is evidence from meta-analyses that some atypical antipsychotic drugs, specifically risperidone and aripiprazole, confer benefit in the treatment of aggression in people with Alzheimer's disease over a period of up to 12 weeks. However, these benefits have to be considered in the context of significant adverse events, including extrapyramidal symptoms, accelerated cognitive decline, stroke and death. In addition, the limited evidence available does not indicate ongoing treatment benefits over longer periods of therapy. The evidence is limited for other pharmacological treatment approaches, but the best evidence is probably for carbamazepine, memantine and citalopram. There is very limited evidence for any therapies in non-Alzheimer dementias. In conclusion, it is important in most situations to limit the use of antipsychotic medication to short-term treatment (up to 12 weeks) of severe neuropsychiatric symptoms to limit harm. Non-pharmacological therapies offer a viable and effective alternative in many situations. Adequately powered randomized controlled trials for the treatment of clinically significant agitation are urgently needed to explore alternative pharmacological therapies. [ABSTRACT FROM AUTHOR]

The article focuses on the behavioral and psychological symptoms of dementia. It mentions that dementia is a significant clinical challenge with an estimation of 35.6 million people with dementia living in the world. Further it mentions that clinical trials focuses on the effectiveness of atypical antipsychotics for the treatment of psychological symptoms of dementia.

Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) account for 10-15% of late onset dementias. Key treatment targets include cognitive and functional impairments, neuropsychiatric symptoms including intense and persistent visual hallucinations, and parkinsonism. Six-month, placebo-controlled randomized controlled trials (RCTs) of the cholinesterase inhibitor rivastigmine have indicated modest but significant benefits in cogni- tion, function, global outcome and neuropsychiatric symptoms in both PDD and DLB. The evidence base for other cholinesterase inhibitors from RCTs is inconclusive. More recent RCTs with memantine in PDD/DLB patients indicate a benefit with regard to global outcome, with some suggestion of a specific benefit with respect to sleep disturbance. Given the risk of severe anti- psychotic sensitivity reactions, antipsychotics should be avoided. A significant proportion of PDD/DLB patients are responsive to levodopa, but care needs to be taken with anti-parkinsonian treatments because of their potential pro- pensity to exacerbate neuropsychiatric symptoms, particularly hallucinations. [ABSTRACT FROM AUTHOR]

Background: Very few interventional studies have directly examined the impact of treatment approaches on health-related quality of life (HRQL) in people with dementia. This is of particular importance in therapies to address behavioural symptoms, where HRQL is often severely affected.Methods: Analysis within the WHELD cluster randomised factorial study in 16 UK care homes examining the impact of person-centred care in combination with antipsychotic review, social interaction and exercise interventions. This study analysed impact on HRQL through the DEMQOL-Proxy.Results: Data on HRQL were available for 187 participants. People receiving antipsychotic review showed a significant worsening in two DEMQOL-Proxy domains (negative emotion: p = 0.02; appearance: p = 0.04). A best-case scenario analysis showed significant worsening for total DEMQOL-Proxy score. Social interaction intervention resulted in a significant benefit to HRQL (p = 0.04). There was no deterioration in HRQL in groups receiving both antipsychotic review and social interaction (p = 0.62).Conclusions: This demonstrates an important detrimental impact of discontinuation of antipsychotics in dementia on HRQL, highlighting the need for careful review of best practice guidelines regarding antipsychotic use and emphasising the importance of providing evidence-based non-pharmacological interventions in conjunction with antipsychotic review. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objectives Apathy is common, impactful, and difficult to manage in people with dementia. We evaluated the efficacy of nonpharmacological interventions, exercise, and social interaction, in combination with antipsychotic review, to reduce apathy in people with dementia living in nursing homes in a cluster randomized controlled trial (RCT). Methods Well-being and health for people with dementia (WHELD) program included a 2 × 2 × 2 factorial cluster RCT involving people with dementia living in 16 nursing homes in the United Kingdom. All homes received training in person-centered care, and were randomized to receive antipsychotic review, social interaction, and exercise, either alone or in combinations. Apathy was one of the secondary outcomes of the WHELD trial, and it was measured by the Neuropsychiatric Inventory–nursing home version at baseline and 9 months (n = 273). We used multilevel mixed effects linear regression models to assess the impact of the interventions on apathy. Results Prevalence of apathy was 44.0% (n = 120; 95% confidence interval [CI] 38.1%–49.9%) at baseline. Severity of apathy had significant positive correlations with dementia severity, neuropsychiatric symptoms, depressive symptoms, agitation, and the needs of the people with dementia ( P < .001). Antipsychotic review reduced antipsychotic use, but it significantly increased apathy (β = 5.37; SE = 0.91; P < . 001). However, antipsychotic review in combination with either social interaction (β = −5.84; SE = 1.15; P < . 001) or exercise (β = −7.54; SE = 0.93; P < . 001) significantly reduced apathy. Conclusions Antipsychotic review can play a significant role in improving apathy in people with dementia living in nursing homes, when combined with psychosocial interventions such as social interaction and exercise. Guidance must be adapted to reflect this subtlety in care. [ABSTRACT FROM AUTHOR]

Objective: This study evaluated the impact of antipsychotic review, social interaction, and exercise, in conjunction with person-centered care, on antipsychotic use, agitation, and depression in people with dementia living in nursing homes.Method: A cluster-randomized factorial controlled trial with two replications was conducted in people with dementia in 16 U.K. nursing homes. All homes received training in person-centered care. Eight homes were randomly assigned to antipsychotic review, to a social interaction intervention, and to an exercise intervention for 9 months, with most homes assigned to more than one intervention. The primary outcome measures were antipsychotic use, agitation, and depression. Secondary outcome measures were overall neuropsychiatric symptoms and mortality.Results: Antipsychotic review significantly reduced antipsychotic use by 50% (odds ratio 0.17, 95% confidence interval [CI] 0.05 to 0.60). Antipsychotic review plus the social interaction intervention significantly reduced mortality (odds ratio 0.26, 95% CI 0.13 to 0.51) compared with the group receiving neither. The group receiving antipsychotic review but not the social intervention showed significantly worse outcome in neuropsychiatric symptoms compared with the group receiving neither (score difference +7.37, 95% CI 1.53 to 13.22). This detrimental impact was mitigated by concurrent delivery of the social intervention (-0.44, CI -4.39 to 3.52). The exercise intervention significantly improved neuropsychiatric symptoms (-3.59, 95% CI -7.08 to -0.09) but not depression (-1.21, CI -4.35 to 1.93). None of the interventions had a significant impact specifically on agitation.Conclusions: While reductions in antipsychotic use can be achieved by using a "real world" intervention, this may not be of benefit to people with dementia in the current climate of more judicious prescribing unless nonpharmacological interventions such as social interaction or exercise are provided in parallel. [ABSTRACT FROM AUTHOR]

Background Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms. Methods The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24 weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI]). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality. Results There was no significant difference between groups on the BADLS or CMAI. At 24 weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI –1.80–2.27; P = .82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI –0.35–8.53; P = .07). Although there were no significant differences in total NPI, there were 5.01 (95% CI –1.68–11.70; P = .05) and 3.63 (95% CI –1.40–8.67; P = .16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24 weeks. Discussion This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk. [ABSTRACT FROM AUTHOR]

Introduction Knowledge regarding the longitudinal course, impact, or treatment implications of pain in people with dementia living in care homes is very limited. Methods We investigated the people with dementia living in 67 care homes in London and Buckinghamshire, United Kingdom. Pain, dementia severity, neuropsychiatric symptoms, depression, agitation, and quality-of-life were measured using appropriate instruments at baseline (N = 967) and after 9 months (n = 629). Results Baseline prevalence of pain was 35.3% (95% CI 32.3–38.3). Pain severity was significantly correlated with dementia severity, neuropsychiatric symptoms, depression, agitation, and quality of life at both time points. Regular treatment with analgesics significantly reduced pain severity. Pain was significantly associated with more antipsychotic prescriptions. Pain was significantly associated (OR 1.48; 95% CI 1.18–1.85) with all-cause mortality during follow-up. Conclusions Pain is an important determinant of neuropsychiatric symptoms, mortality, quality-of-life, and antipsychotic prescriptions. Improved identification, monitoring, and treatment of pain are urgent priorities to improve the health and quality-of-life for people with dementia. [ABSTRACT FROM AUTHOR]

Objectives To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort. Design Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics. Setting Primary and secondary care medical centers in the United States, Canada, Europe, and India. Participants A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis. Interventions Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications (“concurrent APD”) and those who did not take antipsychotic medications at any time during the study (“no APD”). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications. Main Outcome Measures Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson's Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). Results There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13–7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02–4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18–2.29), cognition-related events (IRR 2.70, 95% CI 1.19–5.58), infections (IRR 1.97, 95% CI 1.17–3.16), and edema (IRR 2.61, 95% CI 1.09–5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant. Conclusions This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality. [ABSTRACT FROM AUTHOR]