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To establish the impact of a 3-minute computerized cognitive training program (START) on cognition in older adults with and without genetic risk of Alzheimer's disease. Two-arm randomized controlled trial of the START program. Remote online trial in adults older than 50 taking part from home. The trial compared the START program with placebo in 6544 people older than 50. Primary outcome was executive function measured through Trailmaking B, with other secondary cognitive measures. Genetic risk profile and ApoE4 status were determined by Illumina Array. START conferred benefit to executive function, attention, memory, and a composite measure, including in people with the ApoE4 genotype. The 3-minute START task offers a means of supporting cognitive health in older adults and could be used at scale and within a precision medicine approach to reduce risk of cognitive decline in a targeted way. [ABSTRACT FROM AUTHOR]

Introduction Cognitive training (CT) offers a potential approach for dementia prevention and maintenance of cognitive function in older adults. Online delivery provides a cost-effective means of implementing CT compared with in-person interventions, with the potential of providing an effective public health intervention for risk reduction. Methods A double-blind 6-month online randomized controlled trial in adults older than 50 randomized to General CT, Reasoning CT, or control. The primary outcome was instrumental activities of daily living (IADL) in adults older than 60. Secondary outcomes were reasoning, verbal short-term memory, spatial working memory, verbal learning (VL), and digit vigilance in adults older than 50. Secondary analyses were performed with a group defined as showing age-associated impairment in reasoning according to baseline scores in this domain. Results A total of 2912 adults older than 60 (6742 > 50) participated. General and reasoning packages conferred benefit to IADL ( P = .008, P = .011), reasoning ( P < 0.0001, P < .0001), and VL ( P = .007, P = .008) at 6 months. Benefit in reasoning was evident from 6 weeks. Other benefits developed over 6 months. Analysis of participants with age-associated impairment also showed the same pattern of benefit. A clear dose-response effect was seen. Conclusions Online CT confers significant benefit to cognition and function in older adults, with benefit favoring the Reasoning package. Scale of benefit is comparable with in-person training, indicating its potential as a public health intervention. Impact on the group with age-associated impairment indicates a particular sensitivity to this at-risk group, which merits further investigation. [ABSTRACT FROM AUTHOR]

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]

Context Many older nursing home (NH) residents with cancer experience pain and distressing symptoms. Although some develop cancer during their time in the institution, an increasing number are admitted during their final stages of their lives. Numerous studies have evaluated various treatment approaches, but how pain and symptoms are assessed and managed in people with cancer with and without dementia is unclear. Objectives The objective of this review was to summarize the evidence on cancer-related symptoms among NH residents with and without dementia. Methods We systematically searched the PubMed (1946–2012), Embase (1974–2012), CINAHL (1981–2012), AgeLine, and Cochrane Library (1998–2012) databases using the search terms neoplasms, cancer, tumor, and nursing home. The inclusion criteria were studies including NH residents with a diagnosis of cancer and outcome measures including pain and cancer-related symptoms. Results We identified 11 studies (cross-sectional, longitudinal, clinical trial, and qualitative studies). Ten studies investigated the prevalence and treatment of cancer-related symptoms such as vomiting, nausea, urinary tract infections, and depression. Studies clearly report a high prevalence of pain and reduced prescribing and treatment, regardless of the cognitive status. Only one small study included people with cancer and a diagnosis of dementia. Studies of new cancer diagnoses in NHs could not be identified. Conclusion This review clearly reports a high prevalence of pain and reduced drug prescribing and treatment among NH residents with cancer. This issue appears to be most critical among people with severe dementia, emphasizing the need for better guidance and evidence on pain assessment for these individuals. [ABSTRACT FROM AUTHOR]

Dementia with Lewy bodies is the second most common form of neurodegenerative dementia, yet scarce evidence is available about its prognosis and natural history, which are crucial to inform clinical practice and research. Patients with dementia with Lewy bodies might have a less favourable prognosis, with accelerated cognitive decline, shorter lifespan, and increased admission to residential care than patients with Alzheimer's disease. Health-care costs and, importantly, caregiver burden, are also reported to be higher in dementia with Lewy bodies than in Alzheimer's disease. It is probable that causative factors for this less favourable prognosis are the increased prevalence and early emergence of neuropsychiatric symptoms in patients with dementia with Lewy bodies, and the challenge of accurate diagnosis. Evidence concerning quality of life and hospital admission rates is limited, despite their clinical and economic relevance. [ABSTRACT FROM AUTHOR]

Background: In the absence of disease-modifying treatments, identifying potential psychosocial risk factors for dementia is paramount. Depression and anxiety have been identified as potential risk factors. Studies however have yielded mixed findings, lending possibility to the fact that potential constellations of co-occurring depression and anxiety symptoms may better explain the link between affective symptoms and cognitive decline.Methods: Data from participants (aged 50 and above) of the PROTECT study was used. Latent Class Analysis (LCA) was conducted on 21,684 participants with baseline anxiety and depression measures. Multiple linear regressions models, using a subset of these participants (N = 6136) who had complete cognition data at baseline and at 2-year follow-up, were conducted to assess for associations between class membership and longitudinal changes in cognition.Results: The LCA identified a 5-class solution: "No Symptoms", "Sleep", "Sleep and Worry", "Sleep and Anhedonia", and "Co-morbid Depression and Anxiety". Class membership was significantly associated with longitudinal change in cognition. Furthermore, this association differed across different cognitive measures.Limitations: Limitations included significant attrition and a generally healthy sample which may impact generalisability.Conclusions: Substantial heterogeneity in affective symptoms could explain previous inconsistent findings concerning the association between affective symptoms and cognition. Clinicians should not focus solely on total symptom scores on a single affective domain, but instead on the presence and patterns of symptoms (even if sub-clinical) on measures across multiple affective domains. Identifying particular subgroups that are at greater risk of poor cognitive outcomes may support targeted prevention work. [ABSTRACT FROM AUTHOR]

Digital approaches to delivering person-centered care training to nursing home staff have the potential to enable widespread affordable implementation, but there is very limited evidence and no randomized controlled trials (RCTs) evaluating digital training in the nursing home setting. The objective was to evaluate a digital person-centered care training intervention in a robust RCT. We conducted a 2-month cluster RCT in 16 nursing homes in the United Kingdom, randomized equally to receive a digitally adapted version of the WHELD person-centered care home training program with virtual coaching compared to the digital training program alone. The study was conducted in UK nursing homes. There were 175 participants (45 nursing home staff and 130 residents with dementia). The key outcomes were the well-being and quality of life (QoL) of residents with dementia and the attitudes and knowledge of nursing home staff. There were significant benefits in well-being (t = 2.76, P =.007) and engagement in positive activities (t = 2.34, P =.02) for residents with dementia and in attitudes (t = 3.49, P =.001), including hope (t = 2.62, P =.013) and personhood (t = 2.26, P =.029), for staff in the group receiving digital eWHELD with virtual coaching compared to the group receiving digital learning alone. There was no improvement in staff knowledge about dementia. The study provides encouraging initial clinical trial evidence that a digital version of the WHELD program supported by virtual coaching confers significant benefits for care staff and residents with dementia. Evidence-based digital interventions with remote coaching may also have particular utility in supporting institutional recovery of nursing homes from the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

To examine the bidirectional temporal relationship between depressive symptoms and cognition in relation to risk, reaction, and prodrome. Cross-lag analysis of longitudinal data collected online at baseline and 12-month follow-up. A United Kingdom population cohort of 11,855 participants aged 50 years and over. Patient Health Questionnaire-9 (depressive symptoms), cognitive measures: Paired Associate Learning, Verbal Reasoning, Spatial Working Memory, and Digit Span. Depressive symptoms predicted a decline in paired associates learning [ β = −.020, P =.013, (95% confidence interval [CI], ‒.036, −.004)] and verbal reasoning [ β = −.014, P =.016, (95% CI ‒.025, −.003)] but not vice versa. Depressive symptoms predicted [ β = −.043, P <.001, (95% CI ‒.060, −.026); β = −.029, P <.001, (95% CI ‒.043, −.015)] and were predicted by [ β = −.030, P = <.001, (95% CI ‒.047, −.014); β = −.025, P =.003, (95% CI ‒.041, −.009)], a decline in spatial working memory and verbal digit span, respectively. Depressive symptoms may be either a risk factor or prodrome for cognitive decline. In addition, a decline in attention predicts depressive symptoms. Clinical implications and implications for further research are discussed. [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]

Down's syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. Genetic drivers result in a high frequency of Alzheimer's pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult. Evidence regarding the benefits of cholinesterase inhibitors and other therapeutic options to treat or delay progressive cognitive decline or dementia is very scarce. Despite close similarities with late-onset Alzheimer's disease, individuals with Down's syndrome respond differently to treatment, and a targeted approach to drug development is thus necessary. Genetic and preclinical studies offer opportunities for treatment development, and potential therapies have been identified using these approaches. [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]

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]