Dependence Clusters in Alzheimer Disease and Medicare Expenditures: A Longitudinal Analysis From the Predictors Study.

INTRODUCTION: Dependence in Alzheimer disease has been proposed as a holistic, transparent, and meaningful representation of disease severity. Modeling clusters in dependence trajectories can help understand changes in disease course and care cost over time. METHODS: Sample consisted of 199 initially community-living patients with probable Alzheimer disease recruited from 3 academic medical centers in the United States followed for up to 10 years and had ≥2 Dependence Scale recorded. Nonparametric K-means cluster analysis for longitudinal data (KmL) was used to identify dependence clusters. Medicare expenditures data (1999-2010) were compared between clusters. RESULTS: KmL identified 2 distinct Dependence Scale clusters: (A) high initial dependence, faster decline, and (B) low initial dependence, slower decline. Adjusting for patient characteristics, 6-month Medicare expenditures increased over time with widening between-cluster differences. DISCUSSION: Dependence captures dementia care costs over time. Better characterization of dependence clusters has significant implications for understanding disease progression, trial design and care planning.

Preclinical Alzheimer Disease Drug Development: Early Considerations Based on Phase 3 Clinical Trials.

The number of people in the United States living with Alzheimer disease (AD) is growing, resulting in significant clinical and economic impact. Substantial research investment has led to drug development in stages of AD before symptomatic dementia, such as preclinical AD. Although there are no treatments approved for preclinical AD, there are currently 6 phase 3 clinical trials for preclinical AD treatments. In this article, we review these clinical trials and highlight considerations for future coverage decisions. In line with the definition of preclinical AD, enrollment in these trials focuses on cognitively unimpaired patients that are at high risk of AD because of family history and then genetic testing or brain imaging. Enrollment in most of these trials also allows for younger patients, including those aged under 65 years. Primary clinical trial endpoints focus on cognition often 4 or more years after treatment. Secondary endpoints include other measures of cognition and function, as well as biomarkers. Review of these trials brings to light a few potential considerations when covering these new medications in the future. First, novel and potentially costly approaches involving genetic testing and/or positron emission tomography imaging may be needed to identify appropriate patients and should be developed efficiently. Second, the long duration of these clinical trials suggest that there may be a need for alternative payment approaches in the United States that encourage early payers to pay for a medication for which the long-term benefits may not be realized until after the beneficiary is no longer with the health plan. Third, the value of AD treatments may differ across populations, creating a potential role for indication-based or population-based contracting. Finally, considering the potentially high budgetary impact and little real-world evidence for a new drug class, payers and manufacturers may want to consider outcomes-based payment approaches and coverage with evidence development to mitigate uncertainty about the value of the treatment demonstrated in well-defined populations in clinical trials versus more heterogeneous real-world settings. DISCLOSURES: This work was funded through a generous gift from the Global CEO Initiative on Alzheimer Disease. Hung reports grants from Agency for Healthcare Research and Quality and Pharmaceutical Research and Manufacturers of America outside the submitted work and past employment at CVS Health and BlueCross BlueShield Association. McClellan is an independent board member on the boards of Johnson & Johnson, Cigna, Alignment Healthcare, and Seer; co-chairs the Accountable Care Learning Collaborative and the Guiding Committee for the Health Care Payment Learning and Action Network; and receives fees for serving as an advisor for Cota and MITRE. Hamilton Lopez and Schneider have nothing to disclose. Part of this work was presented at the 2019 AMCP Nexus Meeting, October 29-November 1, 2019, in National Harbor, MD.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil

Objective: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. Method: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. Results: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. Conclusions: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Systems Delivery Innovation for Alzheimer Disease.

OBJECTIVE: The authors describe a comprehensive care model for Alzheimer disease (AD) that improves value within 1-3 years after implementation by leveraging targeted outpatient chronic care management, cognitively protective acute care, and timely caregiver support. METHODS: Using current best evidence, expert opinion, and macroeconomic modeling, the authors designed a comprehensive care model for AD that improves the quality of care while reducing total per capita healthcare spending by more than 15%. Cost savings were measured as reduced spending by payers. Cost estimates were derived from medical literature and national databases, including both public and private U.S. payers. All estimates reflect the value in 2015 dollars using a consumer price index inflation calculator. Outcome estimates were determined at year 2, accounting for implementation and steady-state intervention costs. RESULTS: After accounting for implementation and recurring operating costs of approximately $9.5 billion, estimated net cost savings of between $13 and $41 billion can be accomplished concurrently with improvements in quality and experience of coordinated chronic care ($0.01-$6.8 billion), cognitively protective acute care ($8.7-$26.6 billion), timely caregiver support ($4.3-$7.5 billion), and caregiver efficiency ($4.1-$7.2 billion). CONCLUSION: A high-value care model for AD may improve the experience of patients with AD while significantly lowering costs.

Cost-effectiveness analysis of the treatment of mild and moderate Alzheimer's disease in Brazil.

OBJECTIVE: To perform a cost-effectiveness analysis of donepezil and rivastigmine therapy for mild and moderate Alzheimer's disease (AD) from the perspective of the Brazilian Unified Health System. METHOD: A hypothetical cohort of 1,000 individuals of both sexes, aged >65 years, and diagnosed with AD was simulated using a Markov model. The time horizon was 10 years, with 1-year cycles. A deterministic and probabilistic sensitivity analysis was performed. RESULTS: For mild AD, the study showed an increase in quality-adjusted life years (QALYs) of 0.61 QALY/21,907.38 Brazilian reais (BRL) for patients treated with donepezil and 0.58 QALY/BRL 24,683.33 for patients treated with rivastigmine. In the moderate AD group, QALY increases of 0.05/BRL 27,414.96 were observed for patients treated with donepezil and 0.06/BRL 34,222.96 for patients treated with rivastigmine. CONCLUSIONS: The findings of this study contradict the standard of care for mild and moderate AD in Brazil, which is based on rivastigmine. A pharmacological treatment option based on current Brazilian clinical practice guidelines for AD suggests that rivastigmine is less cost-effective (0.39 QALY/BRL 32,685.77) than donepezil. Probabilistic analysis indicates that donepezil is the most cost-effective treatment for mild and moderate AD.

Anticoagulation Therapy for Atrial Fibrillation in Patients With Alzheimer's Disease.

Background and Purpose- Direct oral anticoagulants (DOACs) are safer, at least equally efficacious, and cost-effective compared to warfarin for stroke prevention in atrial fibrillation (AF) but they remain underused, particularly in demented patients. We estimated the cost-effectiveness of DOACs compared with warfarin in patients with AF and Alzheimer's disease (AD). Methods- We constructed a microsimulation model to estimate the lifetime costs, quality-adjusted life-years (QALYs), and cost-effectiveness of anticoagulation therapy (adjusted-dose warfarin and various DOACs) in 70-year-old patients with AF and AD from a US societal perspective. We stratified patient cohorts based on stage of AD and care setting. Model parameters were estimated from secondary sources. Health benefits were measured in the number of acute health events, life-years, and QALYs gained. We classified alternatives as cost-effective using a willingness-to-pay threshold of $100 000 per QALY gained. Results- For patients with AF and AD, compared with warfarin, DOACs increase costs but also increase QALYs by reducing the risk of stroke. For mild-AD patients living in the community, edoxaban increased lifetime costs by $6603 and increased QALYs by 0.076 compared to warfarin, yielding an incremental cost-effectiveness ratio of $86 882/QALY gained. Even though DOACs increased QALYs compared with warfarin for all patient groups (ranging from 0.019 to 0.085 additional QALYs), no DOAC treatment alternative had an incremental cost-effectiveness ratio <$150 000/QALY gained for patients with moderate to severe AD. For patients living in a long-term care facility with mild AD, the DOAC with the lowest incremental cost-effectiveness ratio (rivaroxaban) costs $150 169 per QALY gained; for patients with more severe AD, the incremental cost-effectiveness ratios were higher. Conclusions- For patients with AF and mild AD living in the community, edoxaban is cost-effective compared with warfarin. Even though patients with moderate and severe AD living in the community and patients with any stage of AD living in a long-term care setting may obtain positive clinical benefits from anticoagulation treatment, DOACs are not cost-effective compared with warfarin for these populations. Compared to aspirin, no oral anticoagulation (warfarin or any DOAC) is cost effective in patients with AF and AD.

Confidentiality in preclinical Alzheimer disease studies: when research and medical records meet.

Clinical trials to advance the diagnosis and treatment of Alzheimer disease (AD) may expose research subjects to discrimination risks. An individual enrolled in a research study that uses positive test results from amyloid PET imaging or CSF measures of ß-amyloid 42 as inclusion criteria has biomarkers indicative of AD pathology. If insurers and employers learn this information, it could expose subjects to discrimination. Unfortunately, current legal and regulatory mechanisms are not sufficient to protect against harms that have significant consequences for subjects. Existing law that prohibits employment and insurance discrimination based on genetic status does not apply to amyloid biomarkers or any other biomarkers for neurodegenerative diseases. Gaps in legal protections fail to protect research subjects from discrimination by long-term care and disability insurers. This risk is particularly concerning because individuals with AD dementia ultimately need long-term care services. To maximize subject protections and advance valuable research, policymakers, investigators, and research institutions must address shortcomings in the design of the electronic medical record, revise laws to limit discrimination, and develop practices that inform research participants of risks associated with loss of confidentiality.

The UP-TECH project, an intervention to support caregivers of Alzheimer's disease patients in Italy: study protocol for a randomized controlled trial.

BACKGROUND: The epidemic of Alzheimer's disease (AD) represents a significant challenge for the health care and social service systems of many developed countries. AD affects both patients and family caregivers, on whom the main burden of care falls, putting them at higher risk of stress, anxiety, mortality and lower quality of life. Evidence remains controversial concerning the effectiveness of providing support to caregivers of AD patients, through case management, counseling, training, technological devices and the integration of existing care services. The main objectives of the UP-TECH project are: 1) to reduce the care burden of family caregivers of AD patients; and 2) to maintain AD patients at home. METHODS/DESIGN: A total of 450 dyads comprising AD patients and their caregivers in five health districts of the Marche region, Italy, will be randomized into three study arms. Participants in the first study arm will receive comprehensive care and support from a case manager (an ad hoc trained social worker) (UP group). Subjects in the second study arm will be similarly supported by a case manager, but in addition will receive a technological toolkit (UP-TECH group). Participants in the control arm will only receive brochures regarding available services. All subjects will be visited at home by a trained nurse who will assess them using a standardized questionnaire at enrollment (M0), 6 months (M6) and 12 months (M12). Follow-up telephone interviews are scheduled at 24 months (M24). The primary outcomes are: 1) caregiver burden, measured using the Caregiver Burden Inventory (CBI); and 2) the actual number of days spent at home during the study period, defined as the number of days free from institutionalizations, hospitalizations and stays in an observation unit of an emergency room. DISCUSSION: The UP-TECH project protocol integrates previous evidence on the effectiveness of strategies in dementia care, that is, the use of case management, new technologies, nurse home visits and efforts toward the integration of existing services in an ambitious holistic design. The analysis of different interventions is expected to provide sound evidence of the effectiveness and cost of programs supporting AD patients in the community. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01700556.

[Using markov model to cost-effectiveness analysis of traditional Chinese medicine interference].

Mild cognitive impairment (MCI) is the transition state between normal aging and AD. There are better detection and treatment methods to screen a population of patients with MCI. Through intervention, the probability of MCI conversion to AD can be significantly reduced. This paper first introduces the concept of cost-effectiveness analysis, reconsiders the concept of cost for the particularity of MCI, and uses QALY to evaluate the health effects of the quality of life. Then measure the health quality of life of elderly MCI population, and use Markov model to study the cost of intervention with traditional Chinese medicine-effectiveness analysis. Finally, according to the QALY measure and CEA results, we draw the conclusion that it's helpful to get early intervention in MCI.

Alzheimer's disease and vascular dementia in developing countries: prevalence, management, and risk factors.

Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

[A contribution to the current discussion on anti-dementia drugs in Germany]. / Ein Beitrag zur aktuellen Antidementivadiskussion in Deutschland.

In Germany, the role of acetylcholinesterase inhibitors in the treatment of Alzheimer's disease (AD) has become a topic of recent discussion. The present article addresses issues which, in the opinion of the authors, have not received sufficient attention. These include the distinction between statistical and clinical significance, outcome parameters, the duration of clinical trials, variability in treatment response and the definition of treatment responders. The authors argue that these issues need to be considered in an in-depth evaluation of acetylcholinesterase inhibitors in the treatment of AD.

[Treatment of Alzheimer's disease utilising the best available evidence-based medicine -- utopia?]. / Therapie der Alzheimer-Demenz mit der besten verfügbaren Evidenz -- eine Utopie?

STUDY OBJECTIVES: To practice evidence-based medicine is considered to improve health care, particularly of chronically ill patients. Taking Alzheimer's as an example the objective of this study is to explore as to how far ambulatory Alzheimer's patients receive the medical treatment with the best evidence available. METHOD: In 2000 and 2002 the health care situation of Alzheimer's disease patients was assessed by conducting telephone interviews with one hundred randomly selected general practitioners and specialists listed in the panel of the Institut fur Medizinische Statistik (IMS -- Institute for Medical Statistics). By means of a standardised questionnaire the interviewees' prescriptions were assessed as well as their knowledge of the medical therapy for Alzheimer's and the use of non-medical therapeutic measures. Besides, the interviewees' prescriptions were checked on the basis of quantitative data taken from the IMS panel. Cholinesterase inhibitors (ChE-I), which are accorded the best evidence presently available in the medical treatment of Alzheimer's, were seen as a marker for the improvement of health care in the course of the study. RESULTS AND CONCLUSIONS: The interviewed physicians considered the evidence of medical Alzheimer's disease therapy with cholinesterase inhibitors high. 67 % of the interviewees would use ChE-I as the drug of first choice if a near relative fell ill with Alzheimer's. However, the ChE-I prescriptions were limited to 13 % in the base year 2000 and to 24 % in the base year 2002. Obviously, the implementation of this medical therapy is hampered by budgetary regulations. The interviewees find it particularly disadvantageous that the prescription of ChE-I may overstrain the budgets allocated to their practices. As a consequence, the effort to improve the quality of health care by implementing evidence-based medicine is thwarted by the increasing pressure on German physicians to prescribe drugs according to economic viability.

Canadian Outcomes Study in Dementia: study methods and patient characteristics.

OBJECTIVE: To describe the methods and patient characteristics of the Canadian Outcomes Study in Dementia (COSID). METHODS: COSID is a 3-year prospective study of dementia patients living in the community at the time of study registration. We assessed patients' cognition, behaviour, and functioning every 6 months, using the Modified Mini-Mental State Examination (3MS), the Neuropsychiatric Inventory (NPI), and the Functional Autonomy Measurement System (SMAF), respectively. We assessed caregivers, using the Zarit Burden Interview (ZBI). Additional information included the Global Deterioration Scale (GDS), patients' driving status, and clinical information including family history, dementia type, concomitant medications, and comorbid conditions. From the patient or caregiver, we collected details of inpatient and outpatient resources used by the patient and (or) caregiver. RESULTS: We enrolled 766 patients from 31 Canadian sites. Overall mean age was 76.8 years, and mean age of onset was 73.1 years. Of the total patients, 98% were white, 54% were women, and 84% were diagnosed with Alzheimer's disease. Mean baseline 3MS was 66.5, NPI was 9.5, and SMAF was 18.30. Of these patients, 48% reported a GDS score of 3 (that is, moderate), 16% reported a GDS score of 4 (that is, moderately severe), and the remaining 36% reported a GDS score of 1 or 2 (that is, mild or very mild). At baseline, 83% of patients received cholinesterase inhibitors, 46% received nonsteroidal antiinflammatory drugs, 39% received vitamin E, and 25% received antidepressants. Adult day care and home help were the largest cost factors in this population, with mean monthly costs of $65 and $64, respectively. We found interesting differences in the resources used among geographic regions and care settings. CONCLUSIONS: COSID is already generating valuable information about treatment patterns, outcomes, and resource use in Canadian patients with dementia. As the data mature, it will be possible to build robust models on treatment effectiveness and costs of care.

[Pharmacotherapy of patients with dementia]. / Pharmakotherapie bei Menschen mit Demenzerkrankungen.

Dementing illnesses present among the most frequent and most consequential psychiatric disorders in old age. They thus constitute a particular challenge for science politics and society as a whole. Knowledge about multifactorial etiological and pathological factors is still rather limited. By way of stratified diagnostic procedures various dementia disorders can be differentiated rather reliably. Anti-dementia drugs can enhance cognitive performance and temporarily slow down the progress of the most frequently occurring dementias (Alzheimer-dementia, vascular dementia). In the treatment of behavioral symptoms in dementia newly developed psychopharmological agents are of particular relevance. They constitute an important element of a multi-modal therapeutic strategy.

Alzheimer's disease: emerging noncholinergic treatments.

With population trends skewing toward a larger percentage of elderly, Alzheimer's disease is projected to afflict many millions in the United States and around the world in the next 50 years. In terms of cost and psychological burden, the anticipated burden of this disease on caregivers and society at large is staggering. It is hoped that, with the development of new insights into the processes of this devastating illness and the development of new medications that may interrupt those processes, the projected incidence and impact of AD may be modified in the near future.

[Pharmaco-economic evaluation of Ginkgo special extract EGb 761 for dementias in Austria]. / Pharmakoökonomische Bewertung von Ginkgo-Spezialextrakt EGb 761 im Indikationsgebiet dementielle Erkrankungen bezogen auf Osterreich.

The aim of the study was to carry out an economic evaluation of the therapeutic effects achievable with ginkgo special extract Egb 761 in dementia in Austria. The care-cost savings that could be achieved with ginkgo special extract Egb 761 therapy were estimated on the basis of the extent to which it delayed growing dependency and an increasing need for care--this being ascertained from the active treatment/placebo differences on GERRI after 6 months of treatment with Egb 761 and evaluated using the rates of the Austrian Federal Care Allowance Law--and compared with the cost of this therapy. The duration of illness, the start and duration of treatment, and the Egb 761 dose were varied in a series of scenarios in a sensitivity analysis. In all the scenarios the care-cost savings exceed the costs of the ginkgo special extract Egb 761 therapy. The cost/savings ratio is most favourable when the treatment is started early and when it is used in patients with dementia of the Alzheimer type. For every month by which the transition from the stage requiring a small to moderate amount of care to the stage requiring considerable or very considerable care can be delayed, one can save 812 [symbol: see text]. Prescribing ginkgo special extract Egb 761 for dementia makes sense from the national economic viewpoint because the product can yield care-cost savings that exceed the cost of the treatment itself.

Acetylcholinesterase treatment--modelling potential demand and auditing practice.

BACKGROUND: Acetylcholinesterase inhibitors represent an entirely novel treatment option for patients with Alzheimer's disease (AD). As such they represent a significant change in practice and a significant cost pressure on funding bodies. OBJECTIVES: To assess the impact of cholinesterase inhibitors on routine clinical practice. METHODS: We estimated potential demand for the compounds taking into account eligibility criteria and prescribing practice agreed between clinicians and funders. We then audited actual prescribing practice assessing whether the estimated demand matched actual demand and whether practice and prescribing criteria were adhered to. RESULTS: Over a two-year period we estimated the demand for treatment at a total of 89 patient years for the population of the audit unit. In practice only 24.5 patient years of therapy were received, the short fall apparently being due to low referral rates for treatment. Prescribing by clinicians matched practice guidelines and a high proportion of three monthly assessments using scales for cognition, function and global state were performed. Using these assessment procedures treatment successes could be differentiated from primary and secondary treatment failures and, where apparently appropriate, treatment could be stopped. CONCLUSION: In the real world of clinical practice demand for treatment in AD is modest but likely to grow and assessment with an aim to identifying those receiving benefit from treatment can be achieved.