Adults with intellectual disabilities and third-wave therapies: A systematic review and meta-ethnography.

BACKGROUND: In recent years, third-wave therapies have risen to prominence. Research into adapting and evaluating third-wave therapies for adults with intellectual disabilities has identified that third-wave therapies are accessible, acceptable, and effective (improving a range of symptoms and skills). METHOD: This meta-ethnography followed Noblit and Hare's approach to synthesising findings from qualitative studies to examine how adults with intellectual disabilities experience third-wave therapy groups. A systematic review of three databases identified 13 studies that met our inclusion criteria. RESULTS: We identified that third-wave therapy groups can be a 'Transformational' process for adults with intellectual disabilities that involves three stages: 'Concealment', 'Opening up' and 'Flourishing'. CONCLUSION: Findings highlight the importance of therapeutic processes; especially, working with defences, and developing and maintaining safety/trust. Recommendations include the development of an objective measure of group safety/trust.

High-Dose Thiamine Supplementation in Older Patients With Heart Failure: A Pilot Randomized Controlled Crossover Trial (THIAMINE-HF).

Background: Thiamine supplementation may improve cardiac function in older adults with heart failure (HF). Our objectives were to determine the following: (i) the feasibility of conducting a large trial of thiamine supplementation in HF; and (ii) the effects of thiamine on clinical outcomes. Methods: We conducted a double-blinded randomized placebo-controlled 2-period crossover feasibility study from June 2018 to April 2021. Adults aged ≥ 60 years with symptomatic HF and reduced ejection fraction (≤ 45%) were included. Participants were randomized to thiamine mononitrate 500 mg, or placebo, for 90 days and were switched to the opposite treatment for 90 days after a 6-week washout period. The primary feasibility outcome was recruitment of 24 participants in 11 months. Results: We screened 330 patients over 21 months to recruit 24 patients. Participants' mean age was 73.4 years. The targets for refusal rate, retention rate, and adherence rate were met. Nonsignificant improvements occurred in left ventricular ejection fraction and N-terminal pro-brain natriuretic peptide (NT-proBNP) level with thiamine. A total of 13 serious adverse events occurred in 7 patients; none were related to the study drug. Conclusions: Although we did not reach our recruitment target, we found high-dose thiamine supplementation to be well tolerated, with potential improvements in biomarker outcomes. A larger trial of thiamine supplementation is warranted.

Introduction: La supplémentation en thiamine peut améliorer la fonction cardiaque chez les personnes âgées atteintes d'insuffisance cardiaque (IC). Nos objectifs visaient à déterminer : (i) la faisabilité d'un essai de grande envergure sur la supplémentation en thiamine lors d'IC ; (ii) les effets de la thiamine sur les résultats cliniques. Méthodes: Nous avons réalisé une étude de faisabilité croisée à double insu et à répartition aléatoire contre placebo sur deux périodes de juin 2018 à avril 2021. Nous avons retenu les adultes de ≥ 60 ans qui avaient une IC symptomatique et une fraction d'éjection réduite (≤ 45 %). Nous avons réparti les participants de façon aléatoire pour recevoir 500 mg de mononitrate de thiamine ou le placebo durant 90 jours, et avons inversé le traitement durant 90 jours après une période de lavage de 6 semaines. Le principal critère de faisabilité était le recrutement de 24 participants en 11 mois. Résultats: Nous avons recruté 24 patients sur les 330 patients sélectionnés durant 21 mois. L'âge moyen des participants était de 73,4 ans. Les cibles des taux de refus, des taux de rétention et des taux d'adhésion ont été atteintes. Avec la thiamine, nous avons observé des améliorations non significatives de la fraction d'éjection ventriculaire gauche et de la concentration de propeptide natriurétique de type B N-terminal (NT-proBNP). Parmi les 13 événements indésirables sérieux qu'ont subis sept patients, aucun n'a été associé au médicament étudié. Conclusions: Bien que nous n'ayons pas atteint notre cible de recrutement, nous avons observé que la supplémentation en thiamine à dose élevée était bien tolérée et qu'il y avait des améliorations potentielles des résultats des biomarqueurs. Un essai de plus grande envergure sur la supplémentation en thiamine est justifié.

Using an arts-based approach to explore the building of social capital at a therapeutic recreation camp.

Therapeutic recreation is beneficial for people with and without disabilities, promoting an empowered, connected, and joyful life. The present study aimed to analyse canvas art created on a therapeutic recreation programme called Recovery Camp, to discover what they reveal about the shared experiences which have occurred. This study utilized an arts-based research method and thematic analysis to discover what participants have communicated via their artwork from ten camps between 2018 and 2019. This study adheres to the COREQ guidelines for qualitative studies. Reflexive thematic analysis produced subthemes which informed three main themes and an identified core meaning of Social Capital. The three main themes were Togetherness and teamwork, Positivity, and Gratitude for Recovery Camp. Based on these findings, canvas art has revealed that shared experiences during a therapeutic recreation camp were positive and connecting. Social capital was created and bridged at Recovery Camp through teamwork and prosocial attitudes. Gratitude has also been disclosed by participants for their shared positive experience.

Experiences of outdoor nature-based therapeutic recreation programs for persons with a mental illness: a qualitative systematic review.

OBJECTIVE: The objective of this review was to identify, appraise, and synthesize the best available evidence related to participation in outdoor nature-based therapeutic recreation programs for adults with a mental illness living in the community. INTRODUCTION: Therapeutic recreation is posited to be beneficial for persons living with a mental illness. Research evidence indicates that therapeutic recreation programs can foster mental health recovery. It is important to understand the effectiveness of this from the perspective of persons living with mental illness how outdoor nature-based therapeutic recreation programs are meaningful and helpful for recovery. INCLUSION CRITERIA: This review considered studies that collected qualitative data on the experiences and perspectives of adults with a mental illness regarding their participation in outdoor nature-based therapeutic recreation programs. METHODS: The databases PsycINFO, CINAHL, MEDLINE, Scopus, and Informit, as well as unpublished sources in gray literature (Google Scholar, OpenGrey), were searched and reference lists were checked to locate any additional studies. Studies published in English were considered, with a date range from inception to 2019. Three reviewers independently assessed the methodological quality of the studies that met the inclusion criteria using the JBI critical appraisal approach for qualitative research. Data were extracted by one reviewer using the standardized qualitative extraction tool and checked for accuracy by three other reviewers. The qualitative research findings were pooled using JBI methodology. The JBI process of meta-aggregation was used to identify categories and synthesized findings, and a level of confidence was assigned to both synthesized findings. RESULTS: Eighteen papers met the inclusion criteria and were included in the data extraction phase. A total of 84 findings were extracted and aggregated into six categories based on similarity of meaning and two synthesized findings. The methodological quality of the studies varied, and the overall level of confidence of the synthesized findings was determined to be moderate. CONCLUSIONS: This review identified that persons living with mental illness perceive outdoor nature-based therapeutic recreation as enjoyable and that therapeutic recreation makes a positive contribution to mental health. Congruent with the literature, therapeutic recreation offers a socially inclusive and psychologically safe environment. The intentionally structured social milieu enhances the formation of social relationships and meaningful connections for persons with mental illness. Elements linked with psychological well-being, such as intrinsic motivation, overcoming perceived challenges, and finding purpose and meaning, are enhanced through participation in therapeutic recreation in outdoor nature-based settings. Increased levels of physical activity, greater self-esteem, and enhanced sense of identity were some of the perceived positive changes. This review provides important insights into the subjective needs of persons with mental illness who undertake therapeutic recreation in outdoor nature-based settings. The qualitative findings can inform health care providers, or those interested in therapeutic recreation programming, to use alongside quantitative evidence of effectiveness to design nature-based therapeutic recreation activities that are meaningful for persons with mental illness. Limitations of the research were that papers published in languages other than English were not searched, and papers not located may have influenced the findings of this review.

Alternative mental health clinical placements: Knowledge transfer and benefits for nursing practice outside mental healthcare settings.

AIM AND OBJECTIVES: To explore whether nursing student's experiences at Recovery Camp have impacted their current nursing practices. BACKGROUND: Recently, there has been a move towards more holistic models of nursing care, which seek to break down barriers of stigmatisation and embrace the tenets of self-determination, to acknowledge people with lived experiences of mental illness and their ability to manage their recovery. In that regard, future health professionals such as nursing students will need to be educated in a manner that recognises the importance of lived experience. In this paper, we propose that Recovery Camp, an alternative clinical placement setting model, enhances clinical practice in multiple domains and is beneficial for both nursing practitioners and people with lived experiences of mental illness, as well as offering an effective nontraditional alternative to conventional clinical placement opportunities. METHODS: This study employed a phenomenological research design, involving individual semi-structured telephone interviews. The Standards for Reporting Qualitative Research (SRQR) checklist was adhered to. RESULTS: Three main themes were identified from the analysis: (a) engagement, (b) understanding mental health and (c) holistic care. "I definitely look at people with mental health conditions in a different light." At Recovery Camp, participants felt that they had greater opportunities for engagement with people with lived experiences, and through this engagement, their preconceptions of mental illness began to change. CONCLUSIONS: Recovery Camp may have facilitated the transfer of knowledge that is more person-centred among nursing students, consequently impacting their current nursing practices. RELEVANCE TO CLINICAL PRACTICE: Nurses should be equipped with mental health skills regardless of their career trajectory. While Recovery Camp represents a promising approach to facilitate knowledge transfer, further investigation will be required to determine which other factors are instrumental. This approach may have wider implications for nursing education.

Experiences of outdoor nature-based therapeutic recreation programs for persons with a mental illness: a qualitative systematic review protocol.

OBJECTIVE: The objective of this review is to identify, appraise and synthesize the best available qualitative evidence on participation in outdoor therapeutic recreation programs for adults with a mental illness living in the community. INTRODUCTION: Therapeutic recreation is posited to be beneficial for persons living with a mental illness. Research indicates that therapeutic recreation programs can foster mental health recovery. It is necessary to understand how nature-based therapeutic recreation programs are beneficial from the perspective of persons living with mental illness. INCLUSION CRITERIA: The review will consider studies that have collected qualitative data on the experiences and perspectives of adults with a mental illness of their participation in nature-based therapeutic recreation programs. METHODS: The databases PsycINFO, CINAHL, MEDLINE, Scopus and Informit and unpublished sources in gray literature databases (Google) will be searched and reference lists will be checked to locate any additional studies. Studies published in English will be considered with no date limit. Two reviewers will independently assess the methodological quality of the studies which meet the inclusion criteria using the Joanna Briggs Institute (JBI) critical appraisal checklist for qualitative research. Data will be extracted by one reviewer using the standardized qualitative extraction tool and checked for accuracy by a second reviewer. The qualitative research findings will be pooled using JBI methodology. The JBI process of meta-aggregation will be used to identify categories and synthesized findings.

Third-wave therapies and adults with intellectual disabilities: A systematic review.

BACKGROUND: Third-wave therapies appear to produce positive outcomes for people without intellectual disabilities. This systematic review aimed to establish which third-wave therapies have been adapted for adults with intellectual disabilities and whether they produced positive outcomes. METHOD: Four databases were searched systematically (PsycINFO, Web of Science, MEDLINE and PubMed), yielding 1,395 results. Twenty studies (N = 109) met the present review's inclusion/exclusion criteria. RESULTS: Included studies used mindfulness-based approaches, dialectical behaviour therapy, compassion focused therapy and acceptance and commitment therapy. Due to considerable heterogeneity in the designs and outcome measures used, a meta-analysis was not possible. CONCLUSIONS: Evidence indicated that third-wave therapies improved mental health symptoms for some and improved challenging/offending behaviour, smoking and mindfulness/acceptance skills for most. These findings must be interpreted with caution due to the low methodological quality of included studies. Future research should build on the current evidence base, using scientifically rigorous designs and standardized measures.

Thiamine versus placebo in older heart failure patients: study protocol for a randomized controlled crossover feasibility trial (THIAMINE-HF).

BACKGROUND: Heart failure (HF) is a major cardiovascular disease with increasing prevalence. Thiamine deficiency occurs in 33% of patients with HF. However, the effectiveness of thiamine supplementation in HF is not known. METHODS: In a placebo-controlled randomized two-period crossover feasibility trial, patients age ≥ 60 years with HF and reduced ejection fraction (HFrEF, EF ≤ 45%) will be randomized to thiamine 500 mg oral capsule once daily or placebo for 3 months, then crossed over to the other intervention after a 6-week washout period. The primary outcome is recruitment rate. Secondary outcomes include feasibility and clinical measures. Feasibility outcomes include refusal rate, retention rate, and compliance rate. Secondary clinical outcomes include left ventricular ejection fraction, peak global longitudinal strain measured by echocardiography, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) quality of life score, and clinical outcomes (all-cause mortality, HF hospitalizations, and HF emergency room visits). DISCUSSION: Thiamine is potentially a safe and low-cost treatment for older patients with HFrEF. Results from this study will inform the feasibility of a large clinical trial with clinical endpoints. The findings will be published in a peer review journal and presented at a relevant conference. This study has received full approval from the Hamilton Integrated Research Ethics Board (18-4537) and Health Canada (210603). This trial is funded by the Hamilton Health Sciences New Investigator Grant (15-387) and the McMaster/St. Peter's Hospital Chair of Aging. TRIAL REGISTRATION: NCT03228030 (ClinicalTrials.gov), registered July 24, 2017.

A multidisciplinary learning experience contributing to mental health rehabilitation.

Purpose People who access health services often have a range of needs that require the involvement of members from a multidisciplinary team. Teaching future health professionals about the importance of a multidisciplinary approach can be challenging. The aim of this paper is to describe a project called Recovery Camp that enhanced multidisciplinary health education through experiential and immersive engagement with people experiencing mental illness. Method Future health professionals and people with a lived experience of mental illness took part in Recovery Camp - an innovative five-day therapeutic recreation initiative in the Australian bush. Results are presented in a case study format and provide the reflective quotes of participants. The quotes were analyzed using a content analysis to identify core concepts. Results Analyses identified a common appreciation of multidisciplinary learning. The interactions among students and between students and consumers, promoted inter-professional practice and a holistic understanding of mental health care. Conclusions An immersive multidisciplinary approach, embedded within a recovery-based programme, enhances students' understanding of the significance of multidisciplinary mental health care and treatment. Implications for Rehabilitation People with a lived experience of mental illness have a range of complex needs that require involvement of members from a multidisciplinary rehabilitation team. This study suggested a multidisciplinary, experiential, immersive health education experience - drawing on the principles of therapeutic recreation - can promote inter-professional rehabilitative practice and an appreciation for holistic mental health care.

Patterns of health service use in community living older adults with dementia and comorbid conditions: a population-based retrospective cohort study in Ontario, Canada.

BACKGROUND: Patients with dementia have increased healthcare utilization and often have comorbid chronic conditions. It is not clear if the increase in utilization is driven by dementia, the comorbidities or both. The objective of this study was to describe the number and types of comorbid conditions in a population-based cohort of older adults with dementia and how the level of comorbidity impacts dementia-related and non-dementia-related health service utilization. METHODS: This study is a retrospective cohort study using multiple linked administrative databases to examine health service utilization and costs of 100,630 community-living older adults living with pre-existing dementia in Ontario, Canada. Comorbid conditions and health service utilization were measured using administrative data (physician visits, emergency department visits, hospitalizations, and homecare contacts). RESULTS: Nearly all, 96.3 %, had at least one comorbid condition, while 18.4 % had five or more comorbid conditions. The most common comorbid conditions were hypertension (77.8 %), and arthritis (66.2 %). All types of utilization increased consistently with the number of comorbid conditions. The average number of dementia-related services tended to be similar across all levels of comorbidity while the average number of non-dementia related visits tended to increase with the level of comorbidity. CONCLUSIONS: Comorbidities in community-living older adults with dementia are common and account for a substantial proportion of health service use and costs in this population. Our results suggest that comprehensive programs that take a holistic view to identify the needs of patients in the context of other comorbidities are required for persons with dementia living in the community.

Ibrutinib in previously treated Waldenström's macroglobulinemia.

BACKGROUND: MYD88(L265P) and CXCR4(WHIM) mutations are highly prevalent in Waldenström's macroglobulinemia. MYD88(L265P) triggers tumor-cell growth through Bruton's tyrosine kinase, a target of ibrutinib. CXCR4(WHIM) mutations confer in vitro resistance to ibrutinib. METHODS: We performed a prospective study of ibrutinib in 63 symptomatic patients with Waldenström's macroglobulinemia who had received at least one previous treatment, and we investigated the effect of MYD88 and CXCR4 mutations on outcomes. Ibrutinib at a daily dose of 420 mg was administered orally until disease progression or the development of unacceptable toxic effects. RESULTS: After the patients received ibrutinib, median serum IgM levels decreased from 3520 mg per deciliter to 880 mg per deciliter, median hemoglobin levels increased from 10.5 g per deciliter to 13.8 g per deciliter, and bone marrow involvement decreased from 60% to 25% (P<0.01 for all comparisons). The median time to at least a minor response was 4 weeks. The overall response rate was 90.5%, and the major response rate was 73.0%; these rates were highest among patients with MYD88(L265P)CXCR4(WT) (with WT indicating wild-type) (100% overall response rate and 91.2% major response rate), followed by patients with MYD88(L265P)CXCR4(WHIM) (85.7% and 61.9%, respectively) and patients with MYD88(WT)CXCR4(WT) (71.4% and 28.6%). The estimated 2-year progression-free and overall survival rates among all patients were 69.1% and 95.2%, respectively. Treatment-related toxic effects of grade 2 or higher included neutropenia (in 22% of the patients) and thrombocytopenia (in 14%), which were more common in heavily pretreated patients; postprocedural bleeding (in 3%); epistaxis associated with the use of fish-oil supplements (in 3%); and atrial fibrillation associated with a history of arrhythmia (5%). CONCLUSIONS: Ibrutinib was highly active, associated with durable responses, and safe in pretreated patients with Waldenström's macroglobulinemia. MYD88 and CXCR4 mutation status affected responses to this drug. (Funded by Pharmacyclics and others; ClinicalTrials.gov number, NCT01614821.).

Interprofessional and integrated care of the elderly in a family health team.

PROBLEM ADDRESSED: Family physicians provide most of the care for the frail elderly population, but many challenges and barriers can lead to difficulties with fragmented, ineffective, and inefficient services. OBJECTIVE OF PROGRAM: To improve the quality, efficiency, and coordination of care for the frail elderly living in the community and to enhance geriatric and interprofessional skills for providers and learners. PROGRAM DESCRIPTION: The Seniors Collaborative Care Program used an interprofessional, shared-care, geriatric model. The feasibility of the program was evaluated through a pilot study conducted between November 2008 and June 2009 at Stonechurch Family Health Centre, part of the McMaster Family Health Team. The core team comprised a nurse practitioner, an FP, and a registered practical nurse. Additional team members included a pharmacist, a dietitian, a social worker, and a visiting geriatrician. Twenty-five seniors were evaluated through the pilot program. Patients were assessed within 5 weeks of initial contact. Patients and practitioners valued timely, accessible, preventive, and multidisciplinary aspects of care. The nurse practitioner's role was prominent in the program, while the geriatrician's clinical role was focused efficiently. CONCLUSION: The family health team is ideally positioned to deliver shared care for the frail elderly. Our model allowed for a short referral time and easy access, which might allow seniors to remain in their environment of choice.

Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial.

BACKGROUND: Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia, but the effect in women with diabetes is unknown. We aimed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes. METHODS: We enrolled women from 25 UK antenatal metabolic clinics in a multicentre randomised placebo-controlled trial. Eligibility criteria were type 1 diabetes preceding pregnancy, presentation between 8 weeks' and 22 weeks' gestation, singleton pregnancy, and age 16 years or older. Women were randomly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E (alpha-tocopherol) or matched placebo daily until delivery. The randomisation sequence was stratified by centre with balanced blocks of eight patients. All trial personnel and participants were masked to treatment allocation. The primary endpoint was pre-eclampsia, which we defined as gestational hypertension with proteinuria. Analysis was by modified intention to treat. This study is registered, ISRCTN27214045. FINDINGS: Between April, 2003, and June, 2008, 762 women were randomly allocated to treatment groups (379 vitamin supplementation, 383 placebo). The primary endpoint was assessed for 375 women allocated to receive vitamins, and 374 allocated to placebo. Rates of pre-eclampsia did not differ between vitamin (15%, n=57) and placebo (19%, 70) groups (risk ratio 0.81, 95% CI 0.59-1.12). No adverse maternal or neonatal outcomes were reported. INTERPRETATION: Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes. However, the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing. FUNDING: The Wellcome Trust.

Resveratrol exerts antiproliferative activity and induces apoptosis in Waldenström's macroglobulinemia.

PURPOSE: Resveratrol (3,4',5-tri-hydroxy-trans-stilbene) is an antioxidant constituent of a wide variety of plant species including grapes. It has gained considerable attention because of its anticancer properties, as shown in solid and hematologic malignancies. Whether resveratrol could inhibit proliferation or induce cytotoxicity in Waldenström's macroglobulinemia (WM) was investigated. EXPERIMENTAL DESIGN: We studied resveratrol-induced inhibition of proliferation and induction of cytotoxicity in WM cell lines, WM primary tumor cells, IgM-secreting cells, and peripheral blood mononuclear cells. The mechanisms of action and different signaling pathways involved were studied using Western blot and gene expression profile analysis. Resveratrol activity was also evaluated in the bone marrow microenvironment. We finally investigated whether or not resveratrol could have any synergistic effect if used in combination with other drugs widely used in the treatment of WM. RESULTS: A schematic image illustrating the location and expression of the aurora kinases A, B, and C during mitosis. Resveratrol inhibited proliferation and induced cytotoxicity against WM cells, IgM-secreting cells, as well as primary WM cells, without affecting peripheral blood mononuclear cells; down-regulated Akt, extracellular signal-regulated kinase mitogen-activated protein kinases, and Wnt signaling pathways, as well as Akt activity; induced cell cycle arrest and apoptosis; and triggered c-Jun-NH(2)-terminal-kinase activation, followed by the activation of intrinsic and extrinsic caspase pathways. Lastly, adherence to bone marrow stromal cells did not confer protection to WM cells against resveratrol-induced cytotoxicity. Furthermore, resveratrol showed synergistic cytotoxicity when combined with dexamethasone, fludarabine, and bortezomib. CONCLUSION: Our data show that resveratrol has significant antitumor activity in WM, providing the framework for clinical trials in this disease.

Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline.

BACKGROUND: The effectiveness of the 5 U.S. Food and Drug Administration-approved pharmacologic therapies for dementias in achieving clinically relevant improvements is unclear. PURPOSE: To review the evidence for the effectiveness of cholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and the neuropeptide-modifying agent memantine in achieving clinically relevant improvements, primarily in cognition, global function, behavior, and quality of life, for patients with dementia. DATA SOURCES: Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE, EMBASE, Allied and Complementary Medicine Database, CINAHL, AgeLine, and PsycINFO from January 1986 through November 2006. STUDY SELECTION: English-language randomized, controlled trials were included in the review if they evaluated pharmacologic agents for adults with a diagnosis of dementia, did not use a crossover design, and had a quality score of at least 3 on the Jadad scale. DATA EXTRACTION: Data were extracted on study characteristics and outcomes, including adverse events. Effect sizes were calculated and data were combined when appropriate. DATA SYNTHESIS: 96 publications representing 59 unique studies were eligible for this review. Both cholinesterase inhibitors and memantine had consistent effects in the domains of cognition and global assessment, but summary estimates showed small effect sizes. Outcomes in the domains of behavior and quality of life were evaluated less frequently and showed less consistent effects. Most studies were of short duration (6 months), which limited their ability to detect delay in onset or progression of dementia. Three studies directly compared different cholinesterase inhibitors and found no differences in cognition and behavior. LIMITATIONS: Limitations of available studies included short duration, inclusion of only patients with mild to moderate Alzheimer disease, poor reporting of adverse events, lack of clear definitions for statistical significance, limited evaluation of behavior and quality-of-life outcomes, and limited direct comparison of different treatments. CONCLUSIONS: Treatment of dementia with cholinesterase inhibitors and memantine can result in statistically significant but clinically marginal improvement in measures of cognition and global assessment of dementia.

Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease.

BACKGROUND: In addition to nonmodifiable genetic risk factors, potentially modifiable factors such as hypertension, hyperlipidemia and environmental exposures have been identified as risk factors for Alzheimer disease. In this article, we provide physicians with practical guidance on risk assessment and primary prevention of Alzheimer disease based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. METHODS: We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that met the following criteria: dementia (all-cause, Alzheimer disease or vascular dementia) as the outcome; longitudinal cohort study; study population broadly reflective of Canadian demographics; and genetic risk factors and general risk factors (e.g., hypertension, education, occupation and chemical exposure) identified. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: Of 3424 articles on potentially modifiable risk factors for dementia, 1719 met our inclusion criteria; 60 were deemed to be of good or fair quality. Of 1721 articles on genetic risk factors, 62 that met our inclusion criteria were deemed to be of good or fair quality. On the basis of evidence from these articles, we made recommendations for the risk assessment and primary prevention of Alzheimer disease. For the primary prevention of Alzheimer's disease, there is good evidence for controlling vascular risk factors, especially hypertension (grade A), and weak or insufficient evidence for manipulation of lifestyle factors and prescribing of medications (grade C). There is good evidence to avoid estrogens and high-dose (> 400 IU/d) of vitamin E for this purpose (grade E). Genetic counselling and testing may be offered to at-risk individuals with an apparent autosomal dominant inheritance (grade B). Screening for the apolipoprotein E genotype in asymptomatic individuals in the general population is not recommended (grade E). INTERPRETATION: Despite the personal and societal burden of dementia, our understanding of genetic predisposition to dementias and the contribution of other risk factors remains limited. More importantly, there are few data to explain the overall risks and benefits of prevention strategies or their impact of risk modification.