Informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders: Systematic review and report from a CCCDTD5 Working Group.

OBJECTIVE: As part of the fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, we assessed the literature on informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders (NCDs) to provide evidence-based recommendations for clinicians and researchers. METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards guidelines. Publications that validated the informant-based tools or described their key properties were reviewed. Quality of the studies was assessed using the modified Quality Assessment tool for Diagnostic Accuracy Studies. RESULTS: Out of 386 publications identified through systematic search, 34 that described 19 informant-based tools were included in the final review. Most of these tools are backed by good-quality studies and are appropriate to use in clinical care or research. The tools vary in their psychometric properties, domains covered, comprehensiveness, completion time, and ability to detect longitudinal change. Based on these properties, we identify different tools that may be appropriate for primary care, specialized memory clinic, or research settings. We also identify barriers to use of these tools in routine clinical practice. CONCLUSION: There are several good-quality tools available to collect informant-report for assessment and monitoring of cognition, behavior, or function in patients with NCDs. Clinicians and researchers may choose a particular tool based on their specific needs such as domains of interest, desired psychometric properties, and feasibility. Further work is needed to make the tools more user-friendly and to adopt them into routine clinical care.

Quetiapine for Psychosis in Parkinson Disease and Neurodegenerative Parkinsonian Disorders: A Systematic Review.

We performed a systematic review of randomized controlled trials to assess the high-level evidence regarding the role of quetiapine in the treatment of psychosis in patients with neurodegenerative parkinsonian disorders. Studies were included in the qualitative review if they (1) enrolled participants with diagnosis of Parkinson disease, Lewy body dementia, or any other neurodegenerative parkinsonian disorders; (2) assessed the efficacy of quetiapine; and (3) evaluated psychotic and motor outcomes using validated tools. Of the 341 manuscripts identified, 7 studies fulfilled our inclusion criteria. The studies' risk of bias was considered low. A total of 241 participants enrolled in these trials. Heterogeneity was high due to inclusion criteria, user definitions, assessment tools, and study design. Although not causing any motor deterioration, quetiapine failed to significantly reduce psychotic symptoms compared to placebo when objectively assessed on the Brief Psychotic Rating Scale, the most frequently reported scale in these studies. High loss to follow-up and dropout rates as well as significant improvement in psychotic symptoms in the placebo groups may have affected measurements of possible positive medication effects.

Prevalence of glaucoma in hospitalized older adults with Alzheimer's disease.

OBJECTIVE: To determine the prevalence of glaucoma in older adults with dementia of the alzheimer's type (DAT). METHODS: retrospective chart review: the prevalence of glaucoma was determined in older adults with a diagnosis of DAT or mixed dementia (DAT with vascular contribution) admitted to the geriatric and neurology units of the Centre hospitalier de l'université de Montréal and the hôpital Maisonneuve-rosemont between april 2008 and april 2009 (n=220; DAT group). they were matched for age and date of hospitalisation to the first 220 individuals without dementia (control group) recruited from other medical units in the same hospitals: gastroenterology, internal medicine or cardiology. a diagnosis of glaucoma was deemed positive if recorded in the chart or if there was a medication compatible with this diagnosis. Chi-square tests were used for between-group comparisons. RESULTS: Subjects' age ranged from 66 to 101 years. the prevalence of glaucoma was 6.8% in our study population (n=30/440). glaucoma was significantly more prevalent in the DAT group (n= 21; 9.5%) than in the control group (n= 9; 4.1%) [χ1² = 5.15; p = 0.023]. CONCLUSIONS: the prevalence of glaucoma was higher in a group of older adults with DAT than in a comparable control group. these results underscore the importance of providing regular eyecare for persons affected by DAT.

The profile of executive functioning in amnestic mild cognitive impairment: disproportionate deficits in inhibitory control.

Amnestic mild cognitive impairment (aMCI) represents a group of individuals who are highly likely to develop Alzheimer's disease (AD). Although aMCI is typically conceptualized as involving predominantly deficits in episodic memory, recent studies have demonstrated that deficits in executive functioning may also be present, and thorough categorization of cognitive functioning in MCI may improve early diagnosis and treatment of AD. We first provide an extensive review of neuropsychology studies that examined executive functioning in MCI. We then present data on executive functioning across multiple sub-domains (divided attention, working memory, inhibitory control, verbal fluency, and planning) in 40 aMCI patients (single or multiple domain) and 32 normal elderly controls (NECs). MCI patients performed significantly worse than NECs in all 5 sub-domains, and there was impairment (>1.0 SD below the mean of NECs) in all sub-domains. Impairment on each test was frequent, with 100% of MCI patients exhibiting a deficit in at least one sub-domain of executive functioning. Inhibitory control was the most frequently and severely impaired. These results indicate that executive dysfunction in multiple sub-domains is common in aMCI and highlights the importance of a comprehensive neuropsychological evaluation for fully characterizing the nature and extent of cognitive deficits in MCI.

CCCDTD5 recommendations on the deprescribing of cognitive enhancers in dementia.

INTRODUCTION: Cognitive enhancers (ie, cholinesterase inhibitors and memantine) can provide symptomatic benefit for some individuals with dementia; however, there are circumstances in which the risks of continuing treatment may potentially outweigh benefits. The decision to deprescribe cognitive enhancers must consider each patient's preferences, treatment indications, current clinical status and symptoms, prognosis, and dementia type. METHODS: The 5th Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5) established a subcommittee of experts to review current evidence on the deprescribing of cognitive enhancers. The questions answered by this group included: When should cognitive enhancers be deprescribed in persons with dementia and mild cognitive impairment? How should cognitive enhancers be deprescribed? And, what clinical factors should be considered when deprescribing cognitive enhancers? RESULTS: Patient and care-partner preferences should be incorporated into all decisions to deprescribe cognitive enhancers. Cognitive enhancers should be discontinued in individuals without ongoing evidence of benefit or when the indication for cognitive enhancer use was inappropriate (eg, mild cognitive impairment). Deprescribing should occur gradually and cognitive enhancers should be reinitiated if patients' cognition or function deteriorates. Cognitive enhancers should be continued in individuals whose neuropsychiatric symptoms improve in response to treatment. Clinicians should not deprescribe cognitive enhancers in individuals with significant neuropsychiatric symptoms until symptoms have stabilized. CONCLUSION: CCCDTD5 deprescribing recommendations provide evidence-informed recommendations related to cognitive enhancer deprescribing that will facilitate shared decision making among patients, care partners, and clinicians.

Pharmacological treatment of Alzheimer disease.

OBJECTIVE: To review the different pharmacological approaches to the cognitive, functional, and behavioural manifestations of Alzheimer disease (AD). METHODS: We searched and critically analyzed the most recent relevant literature on pharmacological treatment of AD. RESULTS: The current pharmacological approach to AD treatment is based on vascular prevention and symptomatic therapy with cholinesterase inhibitors (ChEIs) and memantine, an N-methyl-d-aspartic acid antagonist. Clinical trials of 6- to 12-month duration have shown statistically significant benefits with ChEIs and memantine on cognitive, global, functional, and behavioural outcome measures. In general, these benefits are modest. However, they are dose-dependent and reproducible across studies. Most importantly, these benefits are symptomatic as they do not alter disease course. According to the third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, these agents are considered standard treatment options in AD. We will discuss practical issues related to current pharmacological management, such as setting realistic expectations, management of side effects, switching ChEIs, and the decision to discontinue treatment. The results of clinical trials studying potentially disease-modifying approaches in AD will also be reviewed. Unfortunately, although there remains much promise and enthusiasm, none of these agents has shown consistent benefits, and none are available for use in clinical practice. CONCLUSION: Pharmacological options are presently available for the symptomatic treatment of AD. These treatments provide mild but sustained benefits. Before disease-modifying approaches become available, optimizing the use of the available treatment options is crucial.

Switching cholinesterase inhibitors in older adults with dementia.

BACKGROUND: Cholinesterase inhibitors (ChEIs) represent the mainstay of symptomatic treatment in Alzheimer's disease. Three medications belonging to this class are presently widely available. These agents differ in their individual mechanisms of action and pharmacokinetic properties. Switching ChEIs can be a reasonable option in cases of intolerance or lack of clinical benefit. METHODS: A systematic literature search of switching ChEIs was conducted, and all studies specifically evaluating this issue were identified. Published consensus guidelines were also searched for recommendations on ChEI switching. RESULTS: Eight clinical studies are summarized and discussed. All of these studies are open-label or retrospective and they cannot be readily compared because of heterogeneity in design, number of patients, agents used, and endpoints. Switching in most of these studies was done for both "lack of benefit" or "loss of response" after up to 29 months of treatment. Nevertheless, the majority of studies did not include individuals switched for lack of response after several years of treatment. Lack of satisfactory response or intolerance with the initial agent was not predictive of similar results with the second agent. CONCLUSIONS: In light of these findings, we propose the following practical approach to switching ChEIs: (1) in the case of intolerance, switching to a second agent should be done only after the complete resolution of side-effects following discontinuation of the initial agent; (2) in the case of lack of efficacy, switching can be done overnight, with a quicker titration scheme thereafter; (3) switching ChEIs is not recommended in individuals who show loss of benefit several years after initiation of treatment.

CCCDTD5 recommendations on early and timely assessment of neurocognitive disorders using cognitive, behavioral, and functional scales.

INTRODUCTION: Earlier diagnosis of neurocognitive disorders and neurodegenerative disease is needed to implement preventative interventions, minimize harm, and reduce risk of exploitation in the context of undetected disease. Along the spectrum from subjective cognitive decline (SCD) to dementia, evidence continues to emerge with respect to detection, staging, and monitoring. Updates to previous guidelines are required for clinical practice. METHODS: A subcommittee of the 5th Canadian Consensus Conference on Diagnosis and Treatment of Dementia (CCCDTD) reviewed emerging evidence to address the following: (1) Is there a role for screening at-risk patients without clinical concerns? In what context is assessment for dementia appropriate? (2) What tools can be used to evaluate patients in whom cognitive decline is suspected? (3) What important information can be gained from an informant, using which measures? (4) What instruments can be used to get more in-depth information to diagnose mild cognitive impairment (MCI) or dementia? (5) What is the approach to those with cognitive concerns but without objective changes (ie, SCD)? (6) How do we track response to treatment and change over time? The Grading of Recommendations Assessment, Development, and Evaluation system was used to rate quality of the evidence and strength of the recommendations. RESULTS: We recommend instruments to assess and monitor cognition, behavior, and function across the cognitive spectrum, including reports from patient and informant. We recommend against screening asymptomatic older adults but recommend investigation for self- or informant reports of changes in cognition, emergence of behavioral or psychiatric symptoms, or decline in function or self-care. Standardized assessments should be used for cognitive and behavioral change that have sufficient validity for use in clinical practice. DISCUSSION: The CCCDTD5 provides evidence-based recommendations for detection, assessment, and monitoring of neurocognitive disorders. Although these guidelines were developed for use in Canada, they may also be useful in other jurisdictions.

Impact of vascular risk factors and diseases on cognition in persons with mild cognitive impairment.

BACKGROUND/AIM: To investigate the impact of vascular burden (assessed by the number of vascular risk factors and diseases) on the cognition of persons with amnestic mild cognitive impairment (aMCI). METHODS: This study included 145 participants; 68 meeting criteria for amnesic single-domain or multiple-domain MCI and 77 matched controls. Four cognitive domains were assessed: executive functions, processing speed, episodic memory and general cognitive functioning. RESULTS: A larger vascular burden among aMCI is correlated with lower performance in the executive domain. In addition, persons with aMCI with high vascular burden were more frequently of the multiple domain subtype, whereas persons with no vascular burden were more frequently of the single domain subtype. CONCLUSION: Our findings suggest that the combined effect of multiple vascular risk factors and diseases increases the amount of executive impairment in persons with aMCI. Vascular burden may play an important role in the heterogeneity of aMCI by impairing cognitive functions other than memory.

Detection of cognitive impairment and dementia using the animal fluency test: the DECIDE study.

OBJECTIVES: To evaluate the performance of a one-minute screening test measured against a validated 10-minute screening test for mild cognitive impairment (MCI) in detecting CI in patients aged > or = 65 years with two or more vascular risk factors (VRF). METHODS: Patients (n=1523) aged 65 years or older without documented CI symptoms or dementia with two or more VRF participated in this study set in Canadian primary care practice. Baseline data was collected, followed by the 1-minute animal fluency (AF) test and the 10-minute Montreal Cognitive Assessment (MoCA). Physicians (n=122) completed case reports during patient interviews and reported their diagnostic impression. AF test sensitivity, specificity, and accuracy in predicting a positive MoCA was assessed. RESULTS: Study sample mean age was 79.7 years, 55% were female, 97.6% were Caucasian and 75% had < or = 12 years of education. The AF test and MoCA detected CI in 52 and 56 percent of the study population, respectively. The AF test demonstrated sensitivity, specificity, and accuracy in predicting a positive MoCA of 67 percent each. Physicians diagnostic impression of MCI was reported for 37% of patients, and of dementia for 6%. CONCLUSION: In an elderly population with at least two VRF, using AF can be useful in detecting previously unknown symptoms of CI or dementia. Screening for CI in this high risk population is warranted to assist physician recognition of early CI. The short AF administration time favours its incorporation into clinical practice.

Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF): Methods and Design.

BACKGROUND: Compelling evidence showing a link between atrial fibrillation (AF) and cognitive decline and dementia is accumulating. METHODS: Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) is a prospective, multicentric, double-blind, randomized-controlled trial, recruiting patients with nonvalvular AF and a low risk of stroke. Patients with a high risk of bleeding will be excluded from the study. Participants will be randomized to receive either rivaroxaban (15 mg daily) or standard of care (placebo in patients without vascular disease or acetylsalicylic acid 100 mg daily in patients with vascular disease). RESULTS: The primary outcome is the composite of stroke, transient ischemic attack, and cognitive decline (defined by a decrease in the Montreal Cognitive Assessment score ≥ 3 at any follow-up visit after baseline). Approximately 3250 patients will be enrolled in approximately 130 clinical sites until 609 adjudicated primary outcome events have occurred. CONCLUSIONS: BRAIN-AF determines whether oral anticoagulation therapy with rivaroxaban compared with standard of care reduces the risk of stroke, transient ischemic attack, or cognitive decline in patients with nonvalvular AF and a low risk of stroke.

Diagnosis and treatment of dementia: 3. Mild cognitive impairment and cognitive impairment without dementia.

BACKGROUND: Mild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, 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 had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles published between January 2006 and January 2008. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: We identified 2483 articles, of which 314 were considered to be relevant and of good or fair quality. From a synthesis of the evidence in these studies, we made 16 recommendations. In brief, family physicians should be aware that most types of dementia are preceded by a recognizable phase of mild cognitive decline. They should be familiar with the concepts of mild cognitive impairment and of cognitive impairment, no dementia. Patients with these conditions should be closely monitored because of their increased risk for dementia. Leisure activities, cognitive stimulation and physical activity could be promoted as part of a healthy lifestyle in elderly people and those with mild cognitive impairment. Vascular risk factors should be treated optimally. No other specific therapies can yet be recommended. INTERPRETATION: Physicians will increasingly see elderly patients with mild memory loss, and learning an approach to diagnosing states such as mild cognitive impairment is now warranted. Close monitoring for progression to dementia, promotion of a healthy lifestyle and treatment of vascular risk factors are recommended for the management of patients with mild cognitive impairment.

The role of functional assessment as an outcome measure in antidementia treatment.

Functional assessment refers to the evaluation of performance in basic activities of daily living, instrumental activities of daily living, professional duties, and hobbies. This assessment is particularly relevant in the evaluation of cognitive impairment. In fact, functional decline represents a core feature of dementia according to the DSM-IV criteria. Clinically, functional deterioration represents a diagnostic marker, can be used to chart the course of the disease, and as a prognostic marker as it contributes significantly to caregiver burden and institutionalization. For all these reasons, functional assessment has been widely used as an outcome measure in intervention trials of Alzheimer disease (AD). Appropriate function assessment scales have been developed for use in clinical trials of AD. Studies have shown that functional decline benefits from pharmacological interventions in AD and some other cognitive syndromes. This benefit translates into a stabilization ranging between 6 to 12 months compared to a gradual deterioration in the placebo group. There is rarely reversibility for IADL's lost. There are no functional scales specifically designed for assessment of subjects with non-AD cognitive impairment. Scales specifically developed for Mild Cognitive Impairment and other dementias are needed.

Mild cognitive impairment and cognitive impairment, no dementia: Part A, concept and diagnosis.

Mild cognitive impairment (MCI) and cognitive impairment, no dementia (CIND) are controversial emerging terms that encompass the clinical state between elderly normal cognition and dementia. This article reviews recent work on the classification of MCI and CIND, their prognosis, and diagnostic approaches and presents evidence-based recommendations approved at the meeting of the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD3) held in Montreal in March, 2006. New short tools such as the Montreal Cognitive Assessment are making it easier for family physicians to confidently attach the label of MCI.

Mild cognitive impairment and cognitive impairment, no dementia: Part B, therapy.

Mild cognitive impairment (MCI) and cognitive impairment, no dementia (CIND) might be the optimum stage at which to intervene with preventative therapies. This article reviews recent work on the possible treatment and presents evidence-based recommendations approved at the meeting of the Third Consensus Conference on the Diagnosis and Treatment of Dementia held in Montreal in March, 2006. A number of promising nonpharmacologic interventions have been examined. Associations exist with both cognitive and physical activity that suggest that both of these, together or separately, can delay progression to dementia. Similarly, case control studies as well as prospective long-term studies suggest a number of low toxicity interventions and supplements that might significantly impact on MCI progression; folate, B(6), and B(12) to lower homocysteine levels, omega-fatty acids, and anti-oxidants (fruit juices or red wine) are good examples. In selected genotypes such as individuals with APOE e4, therapy with donepezil might slow progression. The concern, however, is that none of these therapies (including cholinesterase inhibitors) have demonstrated a clinically meaningful effect with randomized, placebo-controlled studies. Just as randomized controlled studies have failed to support primary prevention of dementia by using estrogen or nonsteroidal anti-inflammatory drugs (NSAIDs), there exists the possibility that well-designed randomized controlled trials might fail to definitively demonstrate putative or promising mild cognitive impairment interventions. Pharmacologic interventions and nonpharmacologic therapies, while tantalizing, are currently for the most part insufficiently proven to allow serious consideration by physicians. Recommendation were supported for a general "healthy lifestyle" including physical exercise, healthy nutrition, smoking cessation, and mental stimulation. Close monitoring and treatment of vascular risk factors are justified and were also supported.

[Alzheimer Disease]. / Maladie d'Alzheimer. Mise à jour en 2007.

OBJECTIVE: Alzheimer disease (AD) is the most common form of dementia. There have been many advances in the pharmacological treatment of AD in recent years. This article discusses 2 of these advances: vascular prevention and a new molecule, memantine. QUALITY OF EVIDENCE: The conclusions and recommendations in this article are based on data from studies providing level I and level II evidence. MAIN MESSAGE: Recent data suggest that vascular disease plays an important role in the physiopathology of AD. Memantine is a non-competitive, low-affinity N-methyl-D-aspartate receptor antagonist of glutamate that offers a very attractive efficacy and safety profile for treating moderate to severe AD. CONCLUSION: The prevention and treatment of vascular risk factors should be an integral part of the management of AD. For the treatment of moderate to severe AD, memantine is a new option that is effective and well tolerated.

[Validation of indicators of the management of cognitive impairment in geriatric assessment units]. / Validation d'indicateurs de la prise en charge des atteintes des fonctions cognitives dans les unités d'évaluation gériatrique.

OBJECTIVE: To analyze and adapt a set of quality indicators for assessment and management of patients with cognitive disorders, which are seen very frequently in geriatric assessment units in Quebec. DESIGN: Modified Delphi technique. SETTING: Province of Quebec. PARTICIPANTS: Seven clinicians from 3 different medical faculties in Quebec were selected for their expertise in dementia and geriatric care. METHOD: From among the indicators developed in 2001 using the RAND method, 22 items selected for their relevance to evaluation and management of cognitive disorders were adapted to clinical practice in the Quebec hospital system. These indicators, along with evidence from the literature, were submitted by mail to a panel of experts. The experts were asked to rate, on a scale of 1 to 9, their level of agreement with the indicators in terms of their validity and quality and the need for them to be recorded in patients' medical charts. For an indicator to be retained, it had to be accepted according to its median value, to be rated in the upper third of the scale, and to be approved by the panelists. Indicators not accepted at first were modified according to experts' comments and then re-submitted to the same panel for a second round. RESULTS: Of 22 indicators submitted in the first round, 21 were validated. They covered assessment, investigation, evaluation, treatment, and follow-up. The indicator found questionable was modified and then accepted during the second round. CONCLUSION: This study identified 22 indicators relevant to assessment and management of patients with cognitive disorders in geriatric assessment units. These indicators will serve as a basis for evaluation of dementia in a larger study of the quality of care in all short-term geriatric assessment units in Quebec.