A comparison of self and proxy quality of life ratings for people with dementia and their carers: a European prospective cohort study.

Objectives: To identify correlates of self-rated and proxy-rated quality of life (QoL) in people with dementia on (i) a dementia-specific and (ii) a capability-wellbeing QoL measure at baseline and 12-month follow-up, and to consider such factors in the context of QoL intervention development.Method: Prospective clinical and demographic data were collected from 451 community-dwelling dyads (mild-moderate dementia) across eight European countries. QoL was measured using the QOL-AD and the ICECAP-O. Multivariate modelling identified correlates of self- and proxy-rated QoL at baseline and at 12-month follow-up.Results: Carer's proxy-ratings of QoL were significantly lower than self-ratings at all time-points for both measures. Proxy-ratings declined over time, but self-ratings remained stable. Baseline predictors of greater self-rated QoL were education, and greater functional ability and relationship quality. Greater proxy-rated QoL was associated with education and greater functional ability, relationship quality, carer social support and carer QoL, lower carer anxiety/depression and less severe neuropsychiatric symptoms in people with dementia. At follow-up, greater self-rated QoL was predicted by greater functional ability, relationship quality, carer social support and having a spousal carer. Greater proxy-rated QoL at follow-up was associated with the same factors as at baseline; however, the dyad living together was an additional predictive factor.Conclusion: Both proxy-ratings and self-ratings of QoL should be interpreted with caution and in the context of each individual caregiving relationship. Different functional, psychosocial, relational and contextual factors influence self- and proxy-ratings, and both sets of factors should be considered in the context of QoL intervention development for the dyad.

Access to community care for people with dementia and their informal carers : Case vignettes for a European comparison of structures and common pathways to formal care.

BACKGROUND: People with dementia and their informal carers often do not receive appropriate professional support or it is not received at the right time. OBJECTIVES: Description and comparison of common pathways to formal community dementia care in eight European countries as a part of the transnational Actifcare project. MATERIALS AND METHODS: The German team was responsible for creating an individual case scenario as a starting point. The research teams in Ireland, Italy, the Netherlands, Norway, Portugal, Sweden, and the United Kingdom were then asked to describe a common pathway to formal dementia care by writing their own vignette using the provided individual case scenario. RESULTS: A transnational qualitative content analysis was used to identify the following categories as being the most important: involved professionals, dementia-specific and team-based approaches, proactive roles, and financial aspects. General practitioners (GPs) are described as being the most important profession supporting the access to formal care in all the involved countries. In some countries other professionals take over responsibility for the access procedure. Dementia-specific approaches are rarely part of standard care; team-based approaches have differing significances in each of the countries. Informal carers are mainly proactive in seeking formal care. The Nordic countries demonstrate how financial support enhances access to the professional system. CONCLUSION: Enhanced cooperation between GPs and other professions might optimize access to formal dementia care. Team-based approaches focusing on dementia care should be developed further. Informal carers should be supported and relieved in their role. Financial barriers remain which should be further investigated and reduced.

Health economic evaluation of treatments for Alzheimer's disease: impact of new diagnostic criteria.

The socio-economic impact of Alzheimer's disease (AD) and other dementias is enormous, and the potential economic challenges ahead are clear given the projected future numbers of individuals with these conditions. Because of the high prevalence and cost of dementia, it is very important to assess any intervention from a cost-effectiveness viewpoint. The diagnostic criteria for preclinical AD suggested by the National Institute on Aging and Alzheimer's Association workgroups in combination with the goal of effective disease-modifying treatment (DMT) are, however, a challenge for clinical practice and for the design of clinical trials. Key issues for future cost-effectiveness studies include the following: (i) the consequences for patients if diagnosis is shifted from AD-dementia to predementia states, (ii) bridging the gap between clinical trial populations and patients treated in clinical practice, (iii) translation of clinical trial end-points into measures that are meaningful to patients and policymakers/payers and (iv) how to measure long-term effects. To improve cost-effectiveness studies, long-term population-based data on disease progression, costs and outcomes in clinical practice are needed not only in dementia but also in predementia states. Reliable surrogate end-points in clinical trials that are sensitive to detect effects even in predementia states are also essential as well as robust and validated modelling methods from predementia states that also take into account comorbidities and age. Finally, the ethical consequences of early diagnosis should be considered.

Estimates of Current Capacity for Diagnosing Alzheimer's Disease in Sweden and the Need to Expand Specialist Numbers.

BACKGROUND: The emergence of disease-modifying Alzheimer's (AD) treatments provides new hope to patients and families but concerns have been raised about the preparedness of healthcare systems to provide timely access to such treatments because of a combination of a complex diagnostic process and a large prevalent pool. OBJECTIVES: We assess the preparedness of Sweden, a high-income country known for its dementia-friendly policies, to diagnose AD patients eligible for treatment within a six-month window, given current capacity for specialist evaluations and biomarker testing. We calculate the investment requirements for Sweden to achieve this target over a timeframe of 20 years. DESIGN: Desk research to identify data for population, mortality, disease burden, cost of services and current capacity, expert consultation to inform assumptions about patient journey, and use of a Markov model to predict waiting times. The model simulates the patients' journey through different evaluation stages: initial evaluation by a primary care specialist, neurocognitive testing by an AD specialist, and confirmatory biomarker testing with PET scanning or cerebrospinal fluid (CSF) testing. The model assumes specialist appointments and PET scans are capacity constrained, and patients progress from cognitively normal to MCI and from MCI to dementia in the resulting waiting times. MEASUREMENTS: Projected waiting times for diagnosis of eligibility for disease-modifying Alzheimer's treatment from 2023 to 2042 assuming current capacity, assuming 20% of Swedish residents aged 60 years and above would seek an evaluation for cognitive decline. Investments required to scale capacity up to reach target of providing diagnosis within six months on average. RESULTS: Initial average waiting times for AD specialist appointments would be around 21 months in 2023 and remain around 55 months through 2042, as demand would continue to outstrip supply throughout the 20-year model horizon. Waiting times for biomarker testing would be stable at less than four weeks, as patients would be held up in the queue for their first specialist consultations, and use of CSF testing is widely accepted in Sweden. An additional 25% of AD specialists would have to be added above the current growth trend to reduce waiting times to less than 6 months at an average annual cost of approximately 805 million SEK. The increased cost of volume of biomarker testing would amount to about 106 million SEK per year. CONCLUSIONS: At current capacity, the Swedish healthcare system is unable to provide timely diagnosis of patients eligible for disease-modifying AD treatment. Although future diagnostic technologies, such as digital cognitive assessments and blood tests for the AD pathology, might decrease demand for capacity-constrained services, substantial investments will be required to meet a target of less than six months of waiting time for a diagnosis.

Costs explained by function rather than diagnosis--results from the SNAC Nordanstig elderly cohort in Sweden.

BACKGROUND: Because the prevalence of many brain disorders rises with age, and brain disorders are costly, the economic burden of brain disorders will increase markedly during the next decades. AIM: The purpose of this study is to analyze how the costs to society vary with different levels of functioning and with the presence of a brain disorder. METHODS: Resource utilization and costs from a societal viewpoint were analyzed versus cognition, activities of daily living (ADL), instrumental activities of daily living (IADL), brain disorder diagnosis and age in a population-based cohort of people aged 65 years and older in Nordanstig in Northern Sweden. Descriptive statistics, non-parametric bootstrapping and a generalized linear model (GLM) were used for the statistical analyses. RESULTS: Most people were zero users of care. Societal costs of dementia were by far the highest, ranging from SEK 262,000 (mild) to SEK 519,000 per year (severe dementia). In univariate analysis, all measures of functioning were significantly related to costs. When controlling for ADL and IADL in the multivariate GLM, cognition did not have a statistically significant effect on total cost. The presence of a brain disorder did not impact total cost when controlling for function. The greatest shift in costs was seen when comparing no dependency in ADL and dependency in one basic ADL function. CONCLUSION: It is the level of functioning, rather than the presence of a brain disorder diagnosis, which predicts costs. ADLs are better explanatory variables of costs than Mini mental state examination. Most people in a population-based cohort are zero users of care.

Multimodal Preventive Trial for Alzheimer's Disease: MIND-ADmini Pilot Trial Study Design and Progress.

BACKGROUND: Interventions simultaneously targeting multiple risk factors and mechanisms are most likely to be effective in preventing cognitive impairment. This was indicated in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) testing a multidomain lifestyle intervention among at-risk individuals. The importance of medical food at the early symptomatic disease stage, prodromal Alzheimer's disease (AD), was emphasized in the LipiDiDiet trial. The feasibility and effects of multimodal interventions in prodromal AD are unclear. OBJECTIVES: To evaluate the feasibility of an adapted FINGER-based multimodal lifestyle intervention, with or without medical food, among individuals with prodromal AD. METHODS: MIND-ADmini is a multinational proof-of-concept 6-month randomized controlled trial (RCT), with four trial sites (Sweden, Finland, Germany, France). The trial targeted individuals with prodromal AD defined using the International Working Group-1 criteria, and with vascular or lifestyle-related risk factors. The parallel-group RCT includes three arms: 1) multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); 2) multimodal lifestyle intervention+medical food (Fortasyn Connect); and 3) regular health advice/care (control group). Primary outcomes are feasibility and adherence. Secondary outcomes are adherence to the individual intervention domains and healthy lifestyle changes. RESULTS: Screening began on 28 September 2017 and was completed on 21 May 2019. Altogether 93 participants were randomized and enrolled. The intervention proceeded as planned. CONCLUSIONS: For the first time, this pilot trial tests the feasibility and adherence to a multimodal lifestyle intervention, alone or combined with medical food, among individuals with prodromal AD. It can serve as a model for combination therapy trials (non-pharma, nutrition-based and/or pharmacological interventions).

Incremental patterns in the amount of informal and formal care among non-demented and demented elderly persons: results from a 3-year follow-up population-based study.

OBJECTIVE: Elderly care includes complex interactions between formal services, informal care, morbidity and disabilities. Studies of the incremental effects of formal and informal care are rare and thus the objective was to describe the longitudinal patterns in formal and informal care given to non-demented and demented persons living in a rural area in Sweden. METHODS: Transitions in the Kungsholmen-Nordanstig Project (n=919) was followed up 3 years later (n=579), presented as different combinations of informal and formal care, institutionalization and mortality. Number of hours spent on care was examined by the Resource Utilization in Dementia instrument (RUD). Bootstrapped descriptive statistics and regression models were applied. RESULTS: The overall mortality during follow-up was 34%, and 15% had been institutionalized. Of those who lived at home, those receiving only formal care had been institutionalized to the greatest extent (29%; p<0.05). In terms of hours, informal care decreased amongst demented. The ratio between demented and non-demented was greater at baseline, both regarding informal care (10:1 and 3:1, respectively) and formal care (5:1 and 4:1, respectively). People with mild cognitive decline and no home support at baseline had a great risk of being receiver of care (formal or informal) or dead at follow-up. CONCLUSIONS: The amount of informal care was lower for demented persons still living at home at follow-up than at baseline, probably due to selection effects (institutionalization and mortality). Mild cognitive decline of non-users of care at baseline was strongly associated with receiving care or being dead at follow-up.

The economic impact of dementia in Europe in 2008-cost estimates from the Eurocode project.

OBJECTIVE: Care for demented people is very resource demanding, the prevalence is increasing and there is so far no cure. Cost of illness (CoI) studies are important by identifying the distribution of costs between different payers of care. The European Union (EU) funded the European Collaboration on Dementia (Eurocode) as part of the EU's 2005 work plan of the Community public health programme. Eurocode was administered by Alzheimer Europe. The aim was to describe the economic impact of dementia in Europe in 2008. METHODS: Eurocode's new estimates for dementia prevalence were included in a cost model based on published European CoI papers. For countries where no CoI figures were available, imputation was used. RESULTS: The total CoI of dementia in the EU27 in 2008 was estimated to be €160 billion (€22 000 per demented per year), of which 56% were costs of informal care. The corresponding costs for the whole Europe was €177 billion. In northern Europe, the direct costs are estimated to be considerabe, while the cost of informal care is the major cost component in southern Europe. The sensitivity analysis showed a range for total EU27 costs between €111 and 168 billion. CONCLUSIONS: The estimated CoI in this study is higher than in previous studies. There are also large differences in different European regions. Notwithstanding the methodological challenges, the societal costs of dementia in Europe are very high which in turn have substantial resource impacts on the social and health care systems in Europe.

Do Malnutrition, Sarcopenia and Frailty Overlap in Nursing-Home Residents?

OBJECTIVES: To study the prevalence and overlap between malnutrition, sarcopenia and frailty in a selected group of nursing home (NH) residents. DESIGN: Cross-sectional descriptive study. SETTING: Nursing homes (NH). PARTICIPANTS: 92 residents taking part in an exercise and oral nutritional supplementation study; >75 years old, able to rise from a seated position, body mass index ≤30 kg/m2 and not receiving protein-rich oral nutritional supplements. MEASUREMENTS: The MNA-SF and Global Leadership Initiative on Malnutrition (GLIM) criteria were used for screening and diagnosis of malnutrition (moderate or severe), respectively. Sarcopenia risk was assessed by the SARC-F Questionnaire (0-10p; ≥4=increased risk), and for diagnosis the European Working Group of Sarcopenia in Older People (EWGSOP2) criteria was used. To screen for frailty the FRAIL Questionnaire (0-5p; 1-2p indicating pre-frailty, and >3p indicating frailty), was employed. RESULTS: Average age was 86 years; 62% were women. MNA-SF showed that 30 (33%) people were at risk or malnourished. The GLIM criteria verified malnutrition in 16 (17%) subjects. One third (n=33) was at risk for sarcopenia by SARC-F. Twenty-seven (29%) subjects displayed confirmed sarcopenic according to EWGSOP2. Around 50% (n=47) was assessed as pre-frail or frail. Six people (7%) suffered from all three conditions. Another five (5%) of the residents were simultaneously malnourished and sarcopenic, but not frail, while frailty coexisted with sarcopenia in 10% (n=9) of non-malnourished residents. Twenty-nine (32%) residents were neither malnourished, sarcopenic nor frail. CONCLUSIONS: In a group of selected NH residents a majority was either (pre)frail (51%), sarcopenic (29%) or malnourished (17%). There were considerable overlaps between the three conditions.

Cost analysis of day care centres in Norway.

BACKGROUND: Day care services aim to offer meaningful activities and a safe environment for the attendees and a respite for family caregivers while being cost effective. This study compares the use of formal and informal care in users and non-users of day care centres designed for persons with dementia. METHOD: Users of day care designed for dementia (DC group) and non-users (NDC group) were followed over a period of 24 months or until nursing home admission (NHA) respectively death. Demographic and clinical characteristics were collected at baseline and after 12 and 24 months. The use of care was recorded by Resource Utilization in Dementia (RUD). RESULTS: A total of 257 persons with dementia participated in the study, 181 in the DC group and 76 in the NDC group. Users of day care centres cause higher costs due to the expenses for day care, while neither the use of home nursing, secondary care, informal care nor the time until NHA did show any differences between users and non-users. The overall costs were higher in the DC group at baseline and after 12 months, but this difference was no longer present at the end of the two-year study period. CONCLUSION: Our results indicate no potential cost-saving effect of day care designed for people with dementia, as the use of day care did neither result in a reduced use of care nor in a delay of NHA. Future research should balance the non-monetary benefits of day care against its costs for a full cost-effectiveness analysis, most favourable in a RCT-design.

Formal and Informal Care of Community-Living Older People: A Population-Based Study from the Swedish National Study on Aging and Care.

OBJECTIVES: Study formal and informal care of community-living older people in the Swedish National study of Aging and Care (SNAC). DESIGN: Cross-sectional, population based cohort. SETTING: Three areas in Sweden: Municipality of Nordanstig, Stockholm and Skåne County. PARTICIPANTS: 3,338 persons ≥72 years. MEASUREMENTS: Patterns and amounts of informal and formal care by cognition and area of residence. RESULTS: 73% received no care; 14% formal care; and 17% informal care (7% received both). In the whole study population, including those who used no care, individuals in small municipalities received 9.6 hours of informal care/month; in mid-size municipalities, 6.6; and in urban areas, 5.6. Users of informal care received 33.1 hours of informal care/month in small municipalities, 54.6 in mid-size municipalities and 36.1 in urban areas. Individuals with cognitive impairment received 14.1 hours of informal care/month, 2.7 times more than people with no/slight impairment. In the whole study population, individuals in small municipalities received an average of 3.2 hours of formal care/month; in mid-size municipalities 1.4; and in urban areas, 2.6. Corresponding figures for formal care users were 29.4 hours in small municipalities, 13.6 in mid-size municipalities and 16.7 in urban areas. Formal care users received 7.1 hours, and informal care users, 5.9 hours for each hour/month received by people in the study population as a whole. CONCLUSIONS: More informal than formal care was provided. Informal care is more frequent in small municipalities than urban areas and for those with than without cognitive impairment. The relationship between data on the whole population and the data on users or care indicates that population-based data are needed to avoid overestimates of care.

Underweight, weight loss and related risk factors among older adults in sheltered housing--a Swedish follow-up study.

BACKGROUND: Underweight and weight loss are important factors in detecting malnutrition. OBJECTIVE: To describe underweight, weight loss and related nutritional factors after 12 months among individuals 75 years or older and living in sheltered housing. A further aim was to identify possible risk factors associated with underweight and weight loss. DESIGN: This is a part of a cross-sectional follow-up study from a county in Sweden, examining the disabilities, resources and needs of 719 older adults in sheltered housing units. Data were collected twice, with a 12-month interval using the Resident Assessment Instrument. RESULTS: Among the 503 remaining chronically ill individuals with cognitive and functional disabilities, 35% were classified as underweight at the initial assessment and 38% at the second, a non-significant difference. A further analysis showed 39% had decreased weight, 27% remained stable and 28% gained weight. A weight loss of 5% occurred in 27% of the older adults and a loss of 10% occurred in 14%. Risk factors associated with being underweight and weight loss, using scales derived from the instrument were cognitive and functional decline. Dementia and Parkinson's disease, eating dependencies and constipation were the strongest risk factors when analyzed as single items. CONCLUSION: A high percentage was underweight or exhibited weight loss and several risk factors were identified. Ensuring adequate nutritional status in individuals with a variety of diseases and declining health status is challenging. Increased combined efforts using a wide range of measures, nutritional programs and routines need to be regularly implemented.

Combination Therapy of Anti-Tau and Anti-Amyloid Drugs for Disease Modification in Early-stage Alzheimer's Disease: Socio-economic Considerations Modeled on Treatments for Tuberculosis, HIV/AIDS and Breast Cancer.

Current drugs for treatment of mild to severe dementia of the Alzheimer's type include cholinesterase inhibitors and the NMDA non-competitive receptor antagonist memantine. There is controversy as to the additive benefit of these symptomatic drugs, and their effects are clinically modest. Patients with Alzheimer's disease (AD) are known to have characteristic pathology, including senile plaques with amyloid beta-protein aggregates and neurofibrillary tangles with assembled tau proteins, which start in the hippocampus and spread to neighboring areas. Amyloid and tau modifying drugs are under clinical testing. Based on this pathophysiology, it is crucial to investigate whether anti-amyloid and anti-tau combined therapy would show efficacy in early stage of AD, beyond what could be achieved with anti-amyloid or anti-tau monotherapy. It is equally important to consider the socio-economic implications of such a combination therapy, if effective. We hypothesize that the high costs of combination therapy for early-stage AD patients will require societal and public health initiatives to ensure universal access to AD treatment. In order to better predict these socio-economic implications, we summarize the management of other combination therapies used for tuberculosis, HIV/AIDS, and breast cancer, based on a database search of PubMed and other relevant sources. We put forward a framework for testing a potential anti-amyloid and anti-tau disease modifying combination therapy for early-stage AD patients and present an analysis of the socio-economic implications of such a combination therapy.

The Road Ahead To Cure And Prevent Alzheimer's Disease: Implementing Prevention into Primary Care.

Most old adults receive their health care from their primary care practitioner; as a consequence, as the population ages, the manifestations and complications of cognitive impairment and dementia impose a growing burden on providers of primary care. Current guidelines do not recommend routine cognitive screening for older persons by primary care physicians, although the vast majority recommend a cognitive status assessment and neurological examination for subjects with a cognitive complaint. Also, no clinical practice guidelines recommend interventions in older adults with cognitive impairment in primary care settings. However, primary care physicians need to conduct a review of risks and protective factors associated with cognitive decline and organize interventions to improve or maintain cognitive function. Recent epidemiological studies have indicated numerous associations between lifestyle-related risk factors and incidental cognitive impairment. The development of biomarkers could also help in diagnosis, prognosis, selection for clinical trials, and objective assessment of therapeutic responses. Interventions aimed at cognitive impairment prevention should be pragmatic and easy to implement on a large scale in different health care systems, without generating high additional costs or burden on participants, medical and social care teams.

A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.

OBJECTIVE: To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD. METHODS: Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year. RESULTS: The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Bråne-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population. CONCLUSION: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.

Economic aspects on drug therapy of dementia.

The great number of people suffering from dementia present a great challenge for the health care and social support systems. In a situation where resources are scarce, health economical aspects of dementia care are of great importance in order to identify cost-effective care. However, the literature in this field is limited. There are also aspects where there methodological development is necessary (e.g. informal care, quality of life, long term effects). In the absence of prospective long term data, it is necessary to use pharmacoeconomical models. It is also important to have population based data for the description of how resources and costs are allocated between the different care sectors. Current data show that there is a strong relationship between cognitive functioning and costs. The number of pharmacoeconomical evaluations of drugs influencing on the symptomatology of dementia is low. Available data show that there is support for a view that treatment is cost-neutral or perhaps cost saving which in combination with positive effects in terms of efficacy may indicate cost-effectiveness.

Economic impact of introducing propentofylline for the treatment of dementia in Sweden.

The purpose of this study was to estimate the impact of the introduction of propentofylline, a glial-cell modulator with neuroprotective properties, on the costs of dementia care in Sweden. To estimate the clinical effects of propentofylline treatment on dementia, we conducted a meta-analysis of four double-masked, placebo-controlled, randomized clinical trials and a simulation in a cohort of 57,000 patients with Alzheimer's disease (AD) or vascular dementia (VaD). This cohort represented the fraction of the total AD and VaD population in Sweden with mild-to-moderate disease, the target population for propentofylline treatment. The rate of progression of dementia was expressed in terms of the annual rate of change in score on the Mini-Mental State Examination (MMSE). The costs of care were estimated on the basis of a prospective population-based study. A regression model was used to quantify the costs of dementia care as a function of MMSE score. The estimates obtained were used to calculate and compare the costs of dementia care until death, with or without propentofylline treatment. The sensitivity of the results to a variety of model assumptions was also assessed. The total gross cost for 9 years under the current treatment strategy was SEK (Swedish kronor) 168.06 billion. Including propentofylline in the treatment strategy yielded net savings of SEK 0.8 billion, since the savings in the cost of patient care outweighed the drug acquisition costs. Over 9 years, this saving represents 3.8% of the costs of dementia care in the target population (MMSE score, 15-25 points) and 0.5% of the costs in the total AD and VaD population. The annual savings per patient ranged from SEK 5517 to 6387 during the first 4 years of propentofylline treatment. If an extended neuroprotective effect of propentofylline is assumed, savings increase to SEK 1.6 billion, equivalent to 7.6% of total care costs in the target population and 1.0% in the total population. Savings increase to SEK 14.6 billion if the extended neuro-protective effect is assumed to be effective in an extended target population (MMSE score, 0-25 points) without increased survival. In the sensitivity analysis, most scenarios yielded benefits in favor of propentofylline treatment. The clinical effects of propentofylline translate into meaningful economic effects. The drug acquisition costs are more than offset by the savings achieved in the cost of care. The inclusion of a broader range of outcomes may increase these savings.

The cost-effectiveness of donepezil therapy in Swedish patients with Alzheimer's disease: a Markov model.

This study compared the cost-effectiveness of donepezil, a new cholinesterase inhibitor indicated for the treatment of mild-to-moderate probable Alzheimer's disease (AD), with no treatment. A Markov state transition model was employed to simulate treatment costs based on Swedish epidemiologic data. The Markov states used in the model were defined according to cognitive function, as assessed by the Mini-Mental State Examination. Data on costs and baseline transition probabilities were taken from the Kungsholmen Project, an observational, population-based study of persons aged >75 years in Sweden. Data on the treatment effect were taken from a clinical trial comparing donepezil to placebo over 24 weeks and were applied to the baseline transition probabilities to assess the effect of treating the clinical manifestations of AD in Swedish patients. Also, a within-trial analysis was performed for comparison, using transition probabilities taken from the clinical study. Both models were run for 5 years in half-year cycles, and both demonstrated various degrees of cost savings and improved effectiveness, as measured by increased time in nonsevere disease states. Thus donepezil had superior cost-effectiveness compared with no treatment.

Costs of Mini Mental State Examination-related cognitive impairment.

OBJECTIVE: To investigate the relationship between cognitive impairment, measured with the Mini Mental State Examination (MMSE), and the cost of care. DESIGN: The study uses data from the Kungsholmen project, a population-based study in Sweden in which people 75 years and older were observed over time. The initial study population (n = 1810) was divided into 4 health states based on the MMSE. A Markov model was constructed from the transition probabilities between different states between the first and second phases of the study. The expected cost of cognitive impairment for a period of 10 years was estimated for the cohort of patients studied. MAIN OUTCOME MEASURES AND RESULTS: There was a strong correlation between cognitive impairment in terms of the MMSE and the annual cost of care. A multivariate statistical analysis showed that a decrease in the MMSE by 1 point was associated with an increase in the cost of care of 15,000 Swedish kronor (SEK) [$US2000; 1995 values]. CONCLUSIONS: The results show that large savings are possible if the decline in cognitive functioning can be prevented. The model developed can be used to estimate the impact on cost of care of treatments which reduce the cognitive decline in patients with Alzheimer's disease.