Alzheimer's Disease In Canada Research Articles

Potential of anti-amyloid therapies for patients with Alzheimer disease in Canada.

Potential of anti-amyloid therapies for patients with Alzheimer disease in Canada.

Utilization of Cholinesterase Inhibitors for Alzheimer Disease in Canada


 Due to upcoming Canadian market approvals of biologics for Alzheimer disease, a utilization study was conducted to assess the current utilization patterns and funding criteria for cholinesterase inhibitors (ChEIs) in selected Canadian jurisdictions from 2017 to 2020.
 Most jurisdictions list ChEIs as exception status, special authorization, or limited use drugs except Manitoba; as of 2018, Manitoba lists donepezil and galantamine as regular benefits and rivastigmine as an exception status drug. Additionally, British Columbia and New Brunswick fund galantamine and rivastigmine after a patient is deemed intolerant to donepezil.
 The following are insights from the utilization analysis.
 
 Across Canada, there has been a decrease in the number of beneficiaries and claims for all ChEIs from 2017 to 2020 in all jurisdictions except Manitoba:
 
 There was a 12% reduction in number of beneficiaries and a 17% reduction in the number of total claims from 2017 to 2020.
 In Manitoba, there was an increase in the number of ChEI beneficiaries that peaked in 2018, which corresponds to the formulary changes for donepezil and galantamine during this period.
 
 
 Across Canada, donepezil had the highest market share among all ChEIs each year from 2017 to 2020, which increased from 71.2% in 2017 to 75.8% in 2020. Galantamine had the second-highest market share each year. The market shares for both galantamine and rivastigmine decreased over time, indicating there is a preference for prescribing donepezil to patients with Alzheimer disease.
 
 The greater use of donepezil may be explained by prescriber preferences or coverage criteria for ChEIs (e.g., donepezil is considered first line in British Columbia and New Brunswick).
 
 
 The cumulative costs of all ChEIs paid for by public drug plans across Canada in 2020 was $20,659,136, a decrease of 43% from $36,325,781 in 2017, which corresponds with the decrease in the total number of ChEI beneficiaries.
 
 Donepezil had the highest national total costs, followed by galantamine, then rivastigmine, which corresponds to the market share for each of these drugs. However, on a cost-per-beneficiary basis, donepezil was associated with the lowest cost estimates in each year from 2017 to 2020.
 
 
 
 

Resident-Level Predictors of Dementia Pharmacotherapy at Long-Term Care Admission: The Impact of Different Drug Reimbursement Policies in Ontario and Saskatchewan: Prédicteurs de la pharmacothérapie de la démence au niveau des résidents lors de l'hospitalisation dans des soins de longue durée : l'impact de différentes politiques de remboursement des médicaments en Ontario et en Saskatchewan.

Cholinesterase inhibitors (ChEIs) and memantine are approved for Alzheimer disease in Canada. Regional drug reimbursement policies are associated with cross-provincial variation in ChEI use, but it is unclear how these policies influence predictors of use. Using standardized data from two provinces with differing policies, we compared resident-level characteristics associated with dementia pharmacotherapy at long-term care (LTC) admission. Using linked clinical and administrative databases, we examined characteristics associated with dementia pharmacotherapy use among residents with dementia and/or significant cognitive impairment admitted to LTC facilities in Saskatchewan (more restrictive reimbursement policies; n = 10,599) and Ontario (less restrictive; n = 93,331) between April 1, 2009, and March 31, 2015. Multivariable logistic regression models were utilized to assess resident demographic, functional, and clinical characteristics associated with dementia pharmacotherapy. On admission, 8.1% of Saskatchewan residents were receiving dementia pharmacotherapy compared to 33.2% in Ontario. In both provinces, residents with severe cognitive impairment, aggressive behaviors, and recent antipsychotic use were more likely to receive dementia pharmacotherapy; while those who were unmarried, admitted in later years, had a greater degree of frailty, and recent hospitalizations were less likely. The direction of the association for older age, rural residency, medication number, and anticholinergic therapy differed between provinces. While more restrictive criteria for dementia pharmacotherapy coverage in Saskatchewan resulted in fewer residents entering LTC on dementia pharmacotherapy, there were relatively few differences in the factors associated with use across provinces. Longitudinal studies are needed to assess how differences in prevalence and characteristics associated with use impact patient outcomes.

Risk Factors for Progression of Alzheimer Disease in a Canadian Population: The Canadian Outcomes Study in Dementia (COSID).

To determine risk factors for clinically significant progression during 12 months in patients with mild-to-moderate Alzheimer disease. Community-dwelling patients with mild-to-moderate Alzheimer disease were enrolled in a 3-year prospective study, the Canadian Outcomes Study in Dementia (commonly referred to as COSID), at 32 Canadian sites. Assessments included the Global Deterioration Scale (GDS) for disease severity, the Mini-Mental State Examination (MMSE) for cognition, the Functional Autonomy Measurement System (SMAF) for daily functioning, and the NeuroPsychiatric Inventory (NPI) for behaviour, measured at baseline and at 12 months. Logistic regression identified factors associated with GDS decline, and subsequent stepwise regression identified key independent predictors. Area under the curve (AUC) was then calculated for the model. Among 488 patients (mean age 76.5 years [SD 6.4], MMSE 22.1 [SD4.6], 44.1% male), 225 (46%) showed GDS decline. After adjusting for age, baseline risk factors for deterioration included the following: poorer cognition (lower MMSE score, OR 0.55; 95% CI 0.4 to 0.72 per 5 points, P ≤ 0.001), greater dependence (lower SMAF, OR 0.72; 95% CI 0.63 to 0.83 per 5 points, P ≤ 0.001), and more neuropsychiatric symptoms (higher NPI, OR 1.11; 95% CI 1.02 to 1.2 per 5 points, P = 0.02), with a protective effect of male sex (OR 0.59; 95% CI 0.39 to 0.9, P = 0.02), and higher (worse) GDS score (very mild, compared with mild OR 0.25; 95% CI 0.09 to 0.70, P ≤ 0.01; compared with moderate, OR 0.08; 95% CI 0.03 to 0.23, P < 0.001; compared with moderately severe, OR 0.03; 95% CI 0.01 to 0.11, P < 0.001). The AUC was 73% (P < 0.001) (sensitivity 90% and specificity 33%). The progression of Alzheimer disease in Canada can be predicted using readily available clinical information.

Treatment of Alzheimer Disease: The Past, the Present, and the Future

Can J Psychiatry. 2011;56(10):577-578. Many thanks to the editor-in-chief for this timely opportunity to provide the readers of The Canadian Journal of Psychiatry (The CJP) with an update on the fast-moving field of Alzheimer disease (AD). As detailed in the reviews by Dr Fadi Massoud and Dr Gabriel C Leger1 and by Dr Clive Ballard and colleagues2 in this issue of The CJP, the current symptomatic drugs are only 1 0 years old, cognitive training is still under development, and disease-modifying drugs are under study. This past spring alone you will have seen the publication, in Alzheimer 's & Dementia: the Journal of the Alzheimer 's Association, of revised diagnostic criteria for AD probable at the traditional dementia stage,3 for AD at the predementia stage,4 and even for AD in the presymptomatic stage,5 in Brain, of cognitive training-related plasticity in people with mild cognitive impairment,6 and in The Lancet, of a seminar on the epidemiology and pathophysiology of AD.7 How is Canada doing in the field of AD? The Canadian Study on Health and Aging8 gave us a good head start, with incidence and prevalence figures across the country for the late 1980s against which we will compare later this decade. When Cholinesterase inhibitors (ChEIs) first became available, family doctors were allowed to prescribe these medications and they are following evidence-based guidelines for diagnosis and treatment common to all interested physicians, the latest revision being done in 20069 and the next one scheduled for 2012. A network of specialized memory clinics was created in the early 1990s to facilitate randomized clinical trials for AD in Canada: the Consortium of Canadian Centres for Clinical Cognitive Research (commonly referred to as C5R). This network is 1 of 5, worldwide, currently planning for global prevention studies.10 More recently, the Canadian Institutes of Health Research initiated the International Collaborative Research Strategy for Alzheimer's Disease (commonly referred to as ICRSAD), including partnership with the United States in the Alzheimer Disease Neuro-Imaging (commonly referred to as ADNI) program, with Germany, the United Kingdom, and other European countries in biomarkers and other technical platforms, and with China for 5-year studies. The Alzheimer Society of Canada has been a strong supporter of AD research in Canada, particularly in training young people from different disciplines. The less positive side of treatment of AD in Canada has been the difficulty in obtaining reimbursement for AD medications across the country. The rivastigmine patch is reimbursed only in 1 province, despite the evidence for better tolerability than the oral formulation, which allows 1 0 mg (current maximal dose), compared with 1 5 mg dosing, in a randomized study about to be concluded. Memantine is reimbursed in only 2 provinces, despite the evidence for benefit on agitation and speech impairment, and even in that 1 province memantine is reimbursed only as monotherapy; for example, not with a ChEI, despite growing evidence for the value of combining the 2 drug classes.1112 In the United States and France, these 2 classes of drugs are routinely combined in the moderate stage of AD. There are even greater challenges ahead: if and when treatments become available to significantly slow down disease progression, how will we convince payers to reimburse them? We need to do a better job of finding responders to treatment during phases II and III of drug development: age at onset of symptoms and severity of symptoms may modify which drug to use, apoE genotype and possibly other genes - the pharmacogenomics of AD.13 Clear start and stopping rules will have to be established. It is conceivable that reimbursement will be conditional on positive biomarkers, such as amyloid deposition measured by positron emission tomography scanning or abnormal beta-amyloid and tau protein levels in cerebrospinal fluid. …

The Relation between Disease Severity and Cost of Caring for Patients with Alzheimer Disease in Canada

to characterize the cost of caring for an outpatient in Canada with Alzheimer disease (AD) based on disease severity, and to describe how costs change with increases in disease severity. community-dwelling patients with mild-to-moderate AD were enrolled in a 3-year, naturalistic, observational study. Assessments included cognition (Mini Mental Status Examination), global ratings (Global Deterioration Scale [GDS]), and daily function (Functional Autonomy Measurement System) as part of the Canadian Outcomes Study in Dementia. Direct (medical and nonmedical) and indirect costs were collected using resource use questionnaires. Costs at baseline were compared with costs at follow-up and correlated with disease severity. total costs associated with treating AD were significantly higher with greater disease severity. The mean total cost to treat patients with very mild AD (GDS = 2) was $367 per month, compared with $4063 per month for patients with severe or very severe AD (GDS = 6). From baseline to follow-up, the greatest changes in cost were observed in the group of patients with the most severe AD as measured by all scales. The largest component of total cost was indirect costs at most severity levels, though medication costs contributed the most in patients with very mild AD. Significant independent contributors to cost were being female, having more impaired activities of daily living, and exhibiting more neuropsychiatric symptoms. costs for treating a patient with AD were strongly associated with disease severity, even though none of the patients were institutionalized. Delaying the progression of AD may reduce indirect costs and burden to caregivers.

A retrospective study of cholinesterase inhibitors for Alzheimer's disease: cerebrovascular disease as a predictor of patient outcomes

ABSTRACTBackground: Dementia may be caused by Alzheimer's disease (AD), cerebrovascular disease (CVD), or a combination of both. When CVD is associated with dementia, survival is thought to be reduced. It is unclear whether treatment with cholinesterase inhibitors (ChEIs), which has been found to slow disease progression in AD patients, has similar benefits in vascular forms of dementia.Objectives: The present study was designed to determine whether co-existing CVD is associated with survival or time to nursing home placement (NHP) among AD patients treated with ChEIs. Findings of poorer outcomes in patients with versus without CVD might argue against the use of ChEIs for AD patients in whom CVD co-exists.Methods: A retrospective cohort study was undertaken using the Régie de l’Assurance Maladie du Québec (RAMQ) databases to examine the time to NHP or death for AD patients aged 66+, with or without CVD, treated with ChEIs between July 1, 2000, and June 30, 2003. Because ChEIs are approved only for AD in Canada, a ChEI prescription was used as a surrogate for an AD diagnosis. Separate analyses were performed for patients with persistent ChEI use and those who discontinued ChEI therapy.Results: A total of 4428 patients met inclusion criteria for AD with CVD; 13 512 were classified as having AD alone. For the composite endpoint of NHP or death, 1000-day survival rates were lower among AD patients with versus without CVD (p < 0.01), but absolute differences were very small (84 vs. 86% with continuous ChEI use; 77 vs. 78% with discontinuous ChEI therapy). Of the secondary endpoints, time to death was shorter for patients with versus without CVD, but time to NHP did not differ between groups.Limitations: Results may have been affected by selection (misclassification) bias and between-group differences in smoking, body mass index, and duration of ChEI therapy.Conclusions: Associations between co-existing CVD and time to NHP or death appeared to be of little clinical relevance among AD patients treated with ChEIs. The lack of difference between AD patients with and without CVD suggests that CVD should not be used as a reason to deny AD patients access to ChEI treatment.

Cost-Effectiveness of Memantine Compared with Standard Care in Moderate-to-Severe Alzheimer Disease in Canada

To conduct a cost-effectiveness analysis comparing the addition of memantine to standard care (that is, without acetylcholinesterase inhibitors) with standard care alone in moderate-to-severe Alzheimer disease (AD) in Canada. A 2-year Markov model estimated clinical effects in terms of quality-adjusted life years (QALYs) and time in complete dependence as well as societal costs in four 6-month cycles. Health states were defined by AD severity assessed with the Mini-Mental State Examination (moderate = 10 to 19; severe < 10), by level of dependence in activities of daily living, and by death. Transition probabilities were estimated by combining data of patients with moderate-to-severe AD from all relevant clinical trials. QALYs were estimated from a UK epidemiologic study. The initial distribution and use of medical and support services for each health state was obtained from the Canadian Study on Health and Aging with current estimates of frequency of use and unit prices applied. Compared with standard care, the memantine strategy saved more than 1 month of complete dependence and produced 0.03 additional QALYs, with no additional cost. Probabilistic sensitivity analyses give an 83.3% chance that memantine treatment is cost-neutral, an 89.5% chance of its being cost-effective if the decision maker is willing to pay $20 000 for a QALY, and a 96.2% chance with a willingness to pay $100 000 per QALY. Robustness of results was confirmed through 1-way and scenario-based sensitivity analyses. Our evaluation found that memantine monotherapy produced relevant health benefit, compared with standard care alone, with no additional costs. Results are consistent with other economic evaluations of memantine conducted in Europe and the United States.

Savings in the cost of caring for patients with Alzheimer's disease in Canada: An analysis of treatment with rivastigmine

Objective To estimate per-patient potential cost savings using rivastigmine in the treatment of Alzheimer's disease (AD) in Canada. Background In recent years, new members of a class of pharmaceuticals known as cholinesterase inhibitors have been introduced for the treatment of patients with AD. Two recent studies conducted in the United Kingdom and the United States estimated potential cost savings from the new cholinesterase inhibitor rivastigmine. The present study combined the disease-progression model used in those 2 studies with Canadian costs to estimate per-patient potential savings resulting from the treatment of AD in Canada. Methods Efficacy data from 2 pivotal, phase III clinical trials of rivastigmine were used in a hazard model of disease progression to estimate long-term differences in cognitive functioning between patients receiving rivastigmine and patients receiving no treatment. We used the Mini-Mental State Examination (MMSE) score as our measure of disease progression. We also used Canadian costs of AD care, estimated as a function of MMSE score, to estimate cost savings experienced by treated patients compared with patients receiving no treatment. All costs and cost savings are presented in 1997 Canadian dollars. We used a societal perspective in this analysis. Results Rivastigmine was estimated to delay the transition to more severe stages of AD by up to 188 days for patients with mild AD after 2 years of treatment. For patients with mild-to-moderate and moderate disease, this delay was estimated to be 106 and 44 days, respectively. For patients with the mild stage of AD, estimated average daily cost savings (excluding the cost of rivastigmine) ranged from Can $0.45 per patient per day at 6 months to Can $6.44 per patient per day after 2 years of treatment. For all patients, these estimated average daily cost savings ranged from a low of Can $0.71 per patient per day after 6 months of treatment to a high of Can $4.93 per patient per day after 2 years. Conclusion On average, treatment with rivastigmine yields savings in the direct cost of caring for AD patients that exceed the cost of the drug after 2 years of treatment.

Economic evaluation of donepezil for the treatment of Alzheimer's disease in Canada.

Donepezil is a new drug recently approved in the United States and Canada for the treatment of Alzheimer's disease (AD). We estimated the cost-effectiveness of donepezil 5 mg daily as an adjunct to usual care in the management of persons with mild-to-moderate AD defined as a Mini-Mental Health State Examination (MMSE) score in the range 10 to 26. Treatment effect data as MMSE change-over-baseline scores were obtained from a 30-week placebo-controlled trial of donepezil. MMSE scores beyond observed trial data were estimated using a Markov model with 10 cycles of 24 weeks based on the placebo MMSE progression observed in the trial. Data from AD subjects in the Canadian Study of Health and Aging were used to estimate costs of nursing home care, community services, medications, and caregiver time as a function of MMSE score. A clinic-based cohort study from Alberta was used to estimate the distribution of AD patients by MMSE score presenting for treatment. The effectiveness measure for the economic model was expected time (over 5 years) spent with nonsevere AD (MMSE > or = 10). Over 5 years of treatment, donepezil is predicted to reduce health care costs by CA$929 per patient but increase caregiver time costs by CA$48 per patient for an overall cost saving to society of CA$882 per patient. Patients not receiving donepezil are predicted to spend 2.21 years of the 5 years in nonsevere AD compared with 2.41 years for treated patients (a gain of just over 2 months). Sensitivity analysis reveals that cost savings per patient increase if more AD patients are assumed to survive to 5 years; however, if donepezil treatment continues when patients' MMSE score falls below 10, the incremental cost is higher for treatment at CA$1554 per patient. Based on the limited available data, our model predicts that the use of donepezil for mild-to-moderate AD in Canada is associated with lower 5-year costs and less time spent with severe AD when compared with the alternative of usual care with no donepezil therapy. As more reliable long-term data become available, these predictions should be confirmed and/or updated.