16-Year Survival of the Canadian Collaborative Cohort of Related Dementias.

Background Survival estimates are integral to care for patients diagnosed with dementia. Few Canadian studies have carried out long-term follow-up of well-described cohorts, analyzing survival related to multiple risk factors. Methods Survival analysis of an inception cohort enrolled at a British Columbia (BC) tertiary dementia referral clinic between 1997 and 1999 was undertaken. Vital status was completed for 168 patients diagnosed with dementia. An evaluation of the effects of demographics, vascular risk factors, cognitive and functional ratings, apolipoprotein 4-status, and cholinesterase use on survival was performed using a log-rank test and time-dependent Cox regression. Survival of this dementia cohort was compared with the age-matched life expectancy of persons in BC. Results In all, 158/168 (94.0%) subjects died over 16.6 years, with a median survival of 7.08 years. Risk factors associated with shorter survival in dementia groups included age of onset ≥80 (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.05-2.32); greater functional disability (Disability Assessment for Dementia<55% [HR 1.47, 95% CI 1.04-2.08]); and cumulative medical illness severity (Cumulative Illness Rating Scale≥7 [HR 1.51, 95% CI 1.08-2.12)]. Compared with the BC population, years of potential life lost for dementia subjects aged <65 was 15.36 years, and for dementia subjects aged ≥80 it was 1.82 years. Conclusions Survival in dementia subjects is shorter than population life expectancies for each age strata, with greatest impact on younger patients. For people diagnosed with dementia, age ≥80 years, cumulative medical illness severity, and functional disabilities are the most significant survival predictors and can be used to guide prognosis.

Cognitive functioning, cognitive reserve, and residential care placement in patients with Alzheimer's and related dementias.

OBJECTIVE: To test the hypothesis that patients with mild to moderate dementia with higher initial cognitive reserve (higher education levels exhibit faster cognitive decline at later stages of disease progression as they approach residential care (RC) placement. METHOD: Two provincial administrative databases were used. One contained individuals' scores of cognitive functioning (assessed at 6- to 12-month intervals using the Standardized Mini-Mental State Examination, SMMSE, 2007-2014) and education level; the second (BC Ministry of Health Home and Community Care database, 2001-2014) contained individuals' RC placement; N = 10531. RESULTS: During 2.5-0.5 years prior to placement, SMMSE scores of patients with 0-8 years of education dropped slightly (M D 20.6 to 20.0), while patients with 9-12 years and 13+ years of education started higher (M D 21.8 and 21.4), but decreased faster and ended up lower (M D 19.5 and 18.8). Six-months prior to placement, SMMSE scores of all groups dropped almost 2 points. CONCLUSIONS: Once cognitive reserve of more highly educated dementia patients is depleted and they approach RC placement, their cognitive functioning deteriorates faster. Finding effective interventions that maintain or enhance cognitive reserve may increase the time in the community for dementia patients.

C-TOC (Cognitive Testing on Computer): investigating the usability and validity of a novel self-administered cognitive assessment tool in aging and early dementia.

INTRODUCTION: Cognitive Testing on Computer (C-TOC) is a novel computer-based test battery developed to improve both usability and validity in the computerized assessment of cognitive function in older adults. METHODS: C-TOC's usability was evaluated concurrently with its iterative development to version 4 in subjects with and without cognitive impairment, and health professional advisors representing different ethnocultural groups. C-TOC version 4 was then validated against neuropsychological tests (NPTs), and by comparing performance scores of subjects with normal cognition, Cognitive Impairment Not Dementia (CIND) and Alzheimer disease. C-TOC's language tests were validated in subjects with aphasic disorders. RESULTS: The most important usability issue that emerged from consultations with 27 older adults and with 8 cultural advisors was the test-takers' understanding of the task, particularly executive function tasks. User interface features did not pose significant problems. C-TOC version 4 tests correlated with comparator NPT (r=0.4 to 0.7). C-TOC test scores were normal (n=16)>CIND (n=16)>Alzheimer disease (n=6). All normal/CIND NPT performance differences were detected on C-TOC. Low computer knowledge adversely affected test performance, particularly in CIND. C-TOC detected impairments in aphasic disorders (n=11). DISCUSSION: In general, C-TOC had good validity in detecting cognitive impairment. Ensuring test-takers' understanding of the tasks, and considering their computer knowledge appear important steps towards C-TOC's implementation.

The influence of culture on the oral health-related beliefs and behaviours of elderly chinese immigrants: a meta-synthesis of the literature.

Neglect of the mouth can lead to impairment, disability, and discomfort; as a result, it can have a negative impact on quality of life in old age. Some minority groups in North America shoulder a disproportionate burden of dental impairment compared to people of European origins, possibly because of different cultural beliefs and a distrust of Western oral healthcare. This paper explores these factors in elderly Chinese immigrants through a meta-synthesis of selected literature that reveals a dynamic interplay of traditional Chinese beliefs about oral health, immigration, and structural factors mediating access to Western dentistry. It also identifies several conceptual issues and gaps in knowledge, offers avenues of research including the cross-cultural application of two recent models of oral health, and discusses various strategies for improving access to dental services for minority populations.

Prevalence of mild cognitive impairment and its subtypes in the Mexican population.

BACKGROUND/AIM: To estimate the prevalence of mild cognitive impairment (MCI) and its subtypes, taking into account education and health status. METHODS: This is the first report of our Study on Aging and Dementia in Mexico. This study included 2,944 elderly individuals 60 years old or more with in-home assessment for cognitive impairment. The prevalence of MCI was based on Petersen criteria. MCI was classified as amnestic of single domain (a-MCI-s) or multiple domain (a-MCI-md) or nonamnestic of single domain (na-MCI-s) or multiple domain (na-MCI-md). In addition to a battery of neuropsychological measures, a self-report depression measure and a medical history including history of stroke, heart disease and other health conditions were recorded. RESULTS: The global estimated prevalence of MCI in the Mexican population was 6.45%. Of these subjects, 2.41% met criteria for a-MCI-s, 2.56% for a-MCI-md, 1.18% for na-MCI-s and 0.30% for na-MCl-md. Women showed a higher prevalence of MCI than men (63.7 vs. 36.3%, respectively). The analysis showed that heart disease [odds ratio (OR) 1.5], stroke (OR 1.2) and depression (OR 2.1) were associated with an increased risk of MCI. CONCLUSIONS: The prevalence of MCI in Mexico is similar to that in other countries. The results suggest that stroke, heart disease and depression may have an important role in the etiology of MCI.

Self-efficacy is independently associated with brain volume in older women.

BACKGROUND: ageing is highly associated with neurodegeneration and atrophy of the brain. Evidence suggests that personality variables are risk factors for reduced brain volume. We examine whether falls-related self-efficacy is independently associated with brain volume. METHOD: a cross-sectional analysis of whether falls-related self-efficacy is independently associated with brain volumes (total, grey and white matter). Three multivariate regression models were constructed. Covariates included in the models were age, global cognition, systolic blood pressure, functional comorbidity index and current physical activity level. MRI scans were acquired from 79 community-dwelling senior women aged 65-75 years old. Falls-related self-efficacy was assessed by the activities-specific balance confidence (ABC) scale. RESULTS: after accounting for covariates, falls-related self-efficacy was independently associated with both total brain volume and total grey matter volume. The final model for total brain volume accounted for 17% of the variance, with the ABC score accounting for 8%. For total grey matter volume, the final model accounted for 24% of the variance, with the ABC score accounting for 10%. CONCLUSION: we provide novel evidence that falls-related self-efficacy, a modifiable risk factor for healthy ageing, is positively associated with total brain volume and total grey matter volume. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00426881.

Predictors of patient self-ratings of quality of life in Alzheimer disease: cross-sectional results from the Canadian Alzheimer's Disease Quality of Life Study.

OBJECTIVES: To assess whether the core symptoms of Alzheimer disease (AD) consistently predict patient self-rated quality of life (QOL) as assessed by a variety of QOL measures in a large national sample of AD patients. DESIGN: Cross-sectional. SETTING: Fifteen dementia and geriatric clinics across Canada. PARTICIPANTS: Community-living patients with AD (n = 370) with Mini-Mental State Exam (MMSE) scores greater than 10. MEASUREMENTS: Patients rated their QOL by using two utility indexes, the European QOL-5 Dimensions and the Quality of Well-Being Scale, a global QOL Visual Analog Scale, and the disease-specific QOL-AD instrument. Cognition was assessed with the AD Assessment Scale-Cognitive subscale and MMSE, function with the Disability Assessment for Dementia, and behavioral and psychological symptoms with the Neuropsychiatric Inventory and the Geriatric Depression Scale (GDS). One-way analysis of variance and fully adjusted multiple linear regression were used to assess the relationship between core dementia symptoms and QOL ratings. RESULTS: The QOL measures had only small-to-moderate correlations with each other. For all QOL measures, patient ratings were significantly lower among patients with more depressive symptoms. In multivariable analyses, the GDS score was the only significant independent predictor of patient self-ratings for all four QOL measures. CONCLUSIONS: Self-rated symptoms of depression were a consistent independent predictor of patient-rated QOL across diverse QOL measures, while performance-based measures of cognition and informant-based functional status were not. These findings confirm the importance of identifying and treating depression in patients with AD and endorse the use of measures of self-rated depressive symptoms and QOL as outcomes in AD clinical trials.

Predictors of family caregiver ratings of patient quality of life in Alzheimer disease: cross-sectional results from the Canadian Alzheimer's Disease Quality of Life Study.

OBJECTIVES: To assess whether the core symptoms of Alzheimer disease (AD) and caregiver factors consistently predict family caregiver ratings of patient quality of life (QOL) as assessed by a variety of QOL measures in a large national sample. DESIGN: : Cross-sectional. SETTING: Fifteen dementia and geriatric clinics across Canada. PARTICIPANTS: : Family caregivers (n = 412) of community-living patients with AD of all severities. MEASUREMENTS: Caregiver ratings of patient QOL using three utility indexes, the European Quality of Life-5 Dimensions, Quality of Well-Being Scale and Health Utilities Index; a global QOL visual analogue scale; a disease-specific measure, the Quality of Life-Alzheimer's Disease; and a generic health status measure, the Short Form-36. Patient cognition was assessed with the cognitive subscale of the Alzheimer's Disease Assessment Scale and Mini-Mental State Examination, function with the Disability Assessment for Dementia, and behavioral and psychological symptoms with the Neuropsychiatric Inventory and the Geriatric Depression Scale. Caregiver burden was assessed with the Zarit Burden Interview and caregiver depression with the Center for Epidemiologic Studies Depression scale. One-way analysis of variance and fully adjusted multiple linear regression were used to assess the relationship between patient dementia symptom and caregiver variables with QOL ratings. RESULTS: In multivariable analyses, caregiver ratings of patient function and depressive symptoms were the only consistent independent predictors of caregiver-rated QOL across the QOL measures. CONCLUSIONS: Caregiver ratings of patient function and depression were consistent independent predictors of caregiver-rated QOL, using a spectrum of QOL measures, while measures of patient cognition and caregiver burden and depression were not. These findings support the continued use of caregiver ratings as an important source of information about patient QOL and endorse the inclusion in AD clinical trials of caregiver-rated measures of patient function, depression, and QOL.

Genetic counseling for early-onset familial Alzheimer disease in large Aboriginal kindred from a remote community in British Columbia: unique challenges and possible solutions.

A novel, pathogenic presenilin 1 (PS1) mutation has recently been identified in a large Aboriginal kindred living in dispersed communities throughout British Columbia, Canada. Disseminating genetic information and ensuring that appropriate genetic counseling services are provided to all concerned relatives have posed several unique challenges. These challenges include knowledge exchange and continuity of care in a geographically remote and culturally distinct community. To our knowledge, this is the first time a specific genetic counseling approach has been needed for early-onset familial Alzheimer disease (EOFAD) in a North American Aboriginal community.

Stakeholder opinions on a transformational model of pain management in long-term care.

Pain in older adults with dementia who reside in long-term care (LTC) facilities tends to be undertreated, despite important guidelines designed to ameliorate this problem. A group of public policy and geriatric pain experts recently concluded that existing guidelines are not being implemented because they fail to take into account policy and resource realities. The group published a set of more feasible guidelines that confront these realities (e.g., a recommendation for very brief pain assessments that can be conducted by nursing staff at least weekly). We asked stakeholders to provide opinions on the possibility of implementation of these guidelines within their LTC facilities. Our results support the feasibility of, interest in, and desirability of implementation. They also support an increased role for nurse leadership in LTC pain management. These results could be used to strengthen advocacy efforts for improvement in pain management.

A landscape for training in dementia knowledge translation (DKT).

Meaningful translation of dementia research findings from the bench to the bedside is dependent on the quality of the knowledge to transfer and the availability and skills of investigators engaged in the knowledge translation process. Although there is no shortage of research on dementia, the latter has been more challenging. Results from a survey of 173 researchers from across Canada suggest that workshops and self-paced online training in dementia knowledge translation are needed to bridge the research-to-practice gap. Sharing information among professionals and with the public and formulating actionable messages to policy makers are primary goals.

A novel PS1 gene mutation in a large Aboriginal kindred.

BACKGROUND: There is currently little information on the genetic epidemiology of Alzheimer disease (AD) among North American Aboriginal populations. No cases of familial AD (FAD) in these populations have been published to date. METHODS: Here, we describe a large North American Aboriginal kindred with early onset FAD (EOFAD) in which genetic testing was done. RESULTS AND CONCLUSIONS: A novel Presenilin 1 (PS1) gene mutation (L250F) has been identified. In contrast to the three previously reported families with PS1 codon 250 mutations, affected members of this kindred demonstrate neither myoclonus nor seizures. Furthermore, the identification of a PS1 mutation in a North American Aboriginal kindred presents several unique challenges with respect to knowledge transfer and continuity of care in a geographically remote and culturally distinct community.

Psychological resilience predicts depressive symptoms among spouses of persons with Alzheimer disease over time.

This study examines the three facets of psychological resilience (i.e., perceived control, commitment to living, challenge versus stability) as predictors of depressive symptoms over time among spousal caregivers of persons with Alzheimer disease; these resilience factors were considered over and above dementia-related and socio-demographic control variables. A sample of 105 cohabiting spouses of persons diagnosed with probable or possible Alzheimer disease was recruited for this study. Multilevel modeling enabled us to examine baseline resilience, and the direction and magnitude of change in resilience over time, as distinct predictors of depressive symptoms one year later, and change in depressive symptoms between points of measurement. Both Time 1 control and challenge predicted lower levels of depressive symptoms one year later; furthermore, an increase in challenge over this interval predicted lower Time 2 depressive symptoms. In contrast, commitment did not emerge as a statistically significant predictor of caregiver depression. Findings of this study provide general support for the stress process model of caregiving; in particular, the central role of intra-psychic factors as significant predictors of depressive symptoms over time.

Cognitive impairment no dementia - neuropsychological and neuroimaging characterization of an amnestic subgroup.

BACKGROUND/AIMS: Cognitive impairment no dementia (CIND) describes individuals whose cognitive functioning falls below normal but who do not meet dementia criteria. An important goal within CIND is to identify subgroups that will predictably progress to Alzheimer disease. CIND with amnestic deficits has been associated with high risk of Alzheimer disease but has until now been investigated on a retrospective basis. In this study a prospectively defined amnestic CIND group was characterized on a detailed neuropsychological test battery and on structural magnetic resonance imaging (MRI) measures. METHODS: Amnestic CIND was defined as meeting at least 1 but not all DSM-IV-TR criteria for dementia, scoring > or =1 SD below norms on Rey Auditory Verbal Learning Test delayed recall, having a Clinical Dementia Rating score of 0.5 and a Mini-Mental State Exam score > or =24. This cross-sectional study compared subjects meeting these criteria (n = 25) to age- and education-matched controls (n = 26). The neuropsychological battery included memory and nonmemory measures that were analyzed as continuous variables and dichotomized into impaired (> or =1 SD below controls) versus nonimpaired. MRI scans were evaluated with a global-brain volumetric measure [brain fractional ratio (BFR)] and with visually based medial temporal lobe atrophy (MTA) ratings. RESULTS: Amnestic CIND had neuropsychological impairment in the episodic memory domain and also in nonmemory domains. There were 80% of CIND subjects with multidomain impairment. The most clear-cut nonmemory impairment was in the verbal ability domain, with 64% of subjects affected and a moderate effect size (d = 0.7). On MRI, BFR was lower (74.5 +/- 4.6 vs. 75.5 +/- 4.4) and MTA higher (72 vs. 38% with MTA > or =1) in CIND than in control subjects. BFR correlated with MTA (r = -0.45) and with a composite memory score (r = 0.296). CONCLUSION: A prospective amnestic CIND grouping appears to identify individuals with a multidomain pattern of neuropsychological impairment and with both medial temporal lobe and global brain atrophy.

Consent in Alzheimer's disease research: risk/benefit factors.

In the era of chronic disease, we are challenged to find therapies that provide symptomatic relief and ideally, alter the course of the underlying disease. In Alzheimer's disease (AD), these issues are complicated by the disease itself, which affects the subject's decision-making capacity for participation in the research. According to established ethical guidelines it is clear that individuals with impaired capacity may participate in research and their risk should be no greater than that which the individual would have in day to day activities with anticipation of benefits within that realm. Decision making processes are complex and involve proxies who themselves have biases about their loved one and the potential for participating in the research. Newer disease-modifying approaches such as immunotherapy have potential for affecting the course of the underlying disease but with greater risk of more significant side effects. Ideally the health care of the subjects is not disadvantaged by research participation. At the same time, trials of potentially riskier therapy are relevant in subjects with the disease. Research for subjects with AD must have appropriate safeguards in place to enable effective progress in innovative therapy for a vulnerable, often elderly population. Recommendations are made which could further our capacity to undertake ethical research in the AD population.

Ethical considerations for decision making for treatment and research participation.

Here we review issues of patient decision-making and consent to treatment and research by persons with cognitive impairment and dementia. Clinicians and researchers must recognize their primary duty to care for the individual and must clearly distinguish their role as a clinician and/or researcher. Distinctions between standard care and research must be clearly understood by everyone, as must the clinician's role in each. Both actual and perceived conflicts of interest must be avoided. At present there is insufficient evidence to recommend specific methods for determining competency for decision-making, but a diagnosis of cognitive impairment or dementia does not preclude such competence. Competency is not a unitary or static construct and must be considered as the ability to make an informed decision about participation in the particular context of the specific treatment or study. Clinicians and researchers should consider consent as a process involving both the patient with cognitive impairment and his or her family/caregiver, particularly given the potential that competency for decision-making will change over time. As the availability of advance directives remains limited, clinicians and researchers must make efforts to ensure that decisions made by proxies are based on the prior attitudes and values of the patient.

Disclosure of the diagnosis of dementia.

Most ethical guidelines strongly promote disclosure of a diagnosis of dementia to the affected individual, based on the principle of autonomy. Nevertheless, codes of medical ethics allow for various interpretations of this issue and surveys of clinical practice illustrate that such disclosure is by no means the rule. We argue that diagnostic disclosure for persons with dementia must be considered a process that begins when cognitive impairment is first suspected and that evolves over time as information is obtained. Whenever possible and appropriate, this process should involve not only the affected individual but also their family and/or other current or potential future care providers. Once a diagnosis is established it should be disclosed in a manner consistent with the expressed wishes of the patient, using an individualized patient-centered approach that maintains the individual's personal integrity. Diagnostic disclosure of dementia is a process that may require additional time as well as follow-up or referral to other specialists. We recommend that a progressive disclosure process be employed to address issues including: remaining diagnostic uncertainty, treatment options, future plans, financial planning, assigning power of attorney, wills and "living wills", driving privileges and the need for eventual driving cessation, available support services, and potential research participation. The potential for adverse psychological consequences to diagnostic disclosure must be assessed and these should be addressed through education and support of the patient and their family/caregivers throughout the diagnostic disclosure process. At present, few data are available regarding patients' perspectives on the diagnostic disclosure process and its consequences. This limitation and the apparent discrepancies in physician and caregiver opinions about the disclosure process, make it incumbent upon health care professionals to evaluate the diagnostic disclosure process within their practice.

The 2002 NIMH Provisional Diagnostic Criteria for Depression of Alzheimer's Disease (PDC-dAD): Gauging their Validity over a Decade Later.

Presented herein is evidence for criterion, content, and convergent/discriminant validity of the NIMH-Provisional Diagnostic Criteria for depression of Alzheimer's Disease (PDC-dAD) that were formulated to address depression in Alzheimer's disease (AD). Using meta-analytic and systematic review methods, we examined criterion validity evidence in epidemiological and clinical studies comparing the PDC-dAD to Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV), and International Classification of Disease (ICD 9) depression diagnostic criteria. We estimated prevalence of depression by PDC, DSM, and ICD with an omnibus event rate effect-size. We also examined diagnostic agreement between PDC and DSM. To gauge content validity, we reviewed rates of symptom endorsement for each diagnostic approach. Finally, we examined the PDC's relationship with assessment scales (global cognition, neuropsychiatric, and depression definition) for convergent validity evidence. The aggregate evidence supports the validity of the PDC-dAD. Our findings suggest that depression in AD differs from other depressive disorders including Major Depressive Disorder (MDD) in that dAD is more prevalent, with generally a milder presentation and with unique features not captured by the DSM. Although the PDC are the current standard for diagnosis of depression in AD, we identified the need for their further optimization based on predictive validity evidence.

The Neurocognitive Basis for Impaired Dual-Task Performance in Senior Fallers.

Falls are a major health-care concern, and while dual-task performance is widely recognized as being impaired in those at-risk for falls, the underlying neurocognitive mechanisms remain unknown. A better understanding of the underlying mechanisms could lead to the refinement and development of behavioral, cognitive, or neuropharmacological interventions for falls prevention. Therefore, we conducted a cross-sectional study with community-dwelling older adults aged 70-80 years with a history of falls (i.e., two or more falls in the past 12 months) or no history of falls (i.e., zero falls in the past 12 months); n = 28 per group. We compared functional activation during cognitive-based dual-task performance between fallers and non-fallers using functional magnetic resonance imaging (fMRI). Executive cognitive functioning was assessed via Stroop, Trail Making, and Digit Span. Mobility was assessed via the Timed Up and Go test (TUG). We found that non-fallers exhibited significantly greater functional activation compared with fallers during dual-task performance in key regions responsible for resolving dual-task interference, including precentral, postcentral, and lingual gyri. Further, we report slower reaction times during dual-task performance in fallers and significant correlations between level of functional activation and independent measures of executive cognitive functioning and mobility. Our study is the first neuroimaging study to examine dual-task performance in fallers, and supports the notion that fallers have reduced functional brain activation compared with non-fallers. Given that dual-task performance-and the underlying neural concomitants-appears to be malleable with relevant training, our study serves as a launching point for promising strategies to reduce falls in the future.

Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study.

OBJECTIVES: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation's knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. METHODS: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. RESULTS: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. CONCLUSION: The analysis brings the theoretical framework of "two-eyed seeing" to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease.