| 1. |
- Saha, Sanjib, et al.
(author)
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Economic Evaluation of Interventions for Screening of Dementia
- 2018
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Other publication (other academic/artistic)abstract
- OBJECTIVE: The objective is to systematically review the literature on economic evaluations of screening interventions for early diagnosis of dementia disorders. METHODS: A systematic search of published economic evaluation studies in English was conducted using specified key words in relevant databased and websites. Data extracted included methods and empirical evidence (costs, effects, incremental cost-effectiveness ratio) and we assessed if the conclusions made in terms of cost-effectiveness were supported by the reported evidence. The included studies were also assessed for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Fourteen studies were identified and broadly fell into two groups: screening without biomarkers and screening using biomarkers. There was a considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives as well as types of biomarkers used. The sensitivity and specificity of screening instruments are one of the important aspects in estimating the cost-effectiveness of the interventions. Cost-effectiveness of non-biomarker based interventions cannot be judged due to lack of information. The biomarkers based screening have the potential to be cost-effective but their effectiveness has to be established first. CONCLUSION: More economic evaluations studies as well as good quality effectiveness studies are required in screening strategies before these can be implemented in the clinical practice.
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| 2. |
- Saha, Sanjib, et al.
(author)
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Economic Evaluation of Management of Dementia Patients - A Systematic Literature Review
- 2018
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Other publication (other academic/artistic)abstract
- Objective: The objective is to systematically review the literature on economic evaluations of the interventions for the management of dementia and Alzheimer patients in home, hospital or institutional care. Methods: A systematic search of published economic evaluation studies in English was conducted using specified key words in relevant databased and websites. Data extracted included methods and empirical evidence (costs, effects, incremental cost-effectiveness ratio) and we assessed if the conclusions made in terms of cost-effectiveness were supported by the reported evidence. The included studies were also assessed for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: Twelve studies were identified and there was a considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives as well as types of interventions. Interventions for the management of dementia patients are in general, not cost-effective. Interventions at the community and home setting for managing both the dementia patients and caregivers on a large scale may have the potential to save societal resources. Conclusion: More effectiveness studies as well as good quality economic evaluations are required before implementation decisions on management strategies can be made based on cost-effectiveness.
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| 3. |
- Saha, Sanjib, et al.
(author)
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Economic Evaluation of Nonpharmacological Interventions for Dementia Patients and their Caregivers - A Systematic Literature Review
- 2018
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Other publication (other academic/artistic)abstract
- Background: The rising prevalence of dementia represents an important public health issue. There is currently no available cure for dementia disorders, only symptom-relieving therapies which can be either pharmacological or non-pharmacological. The number of non-pharmacological interventions for patients with dementia disorders and their caregivers have been increasing in recent years without much knowledge on their cost-effectiveness. The objective is to review the existing evidence on cost-effectiveness of non-pharmacological interventions targeting patients with dementia disorders, their caregivers, and the patient-caregiver dyad. Method: A systematic search of published economic evaluation studies in English was conducted using specified key words in relevant databased and websites. Data extracted included methods and empirical evidence (costs, effects, ICER) and we assessed if the conclusions made in terms of cost-effectiveness were supported by the reported evidence. The included studies were also assessed for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results: We included seventeen studies in this review categorised into three groups: physical exercise, occupational therapy, and psychological/psychosocial treatment. In almost all the studies (except one), economic evaluation was performed for a randomised controlled trial alongside the non-pharmacological intervention or retrospectively. There was a considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives as well as types of intervention. This prevents an informative comparison between most of the studies. However, we found that physical exercise was the most-effective non-pharmacological interventions for patients with dementia. For occupational therapy and psychological/psychosocial interventions we found mixed results although the majority was not cost-effective. Conclusion: More economic evaluations studies are required in non-pharmacological interventions. However, the interventions need to have a strong study design with the intention to perform economic evaluation in parallel.
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| 4. |
- Saha, Sanjib, et al.
(author)
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Economic Evaluation of Pharmacological Treatments in Dementia Disorders - A Systematic Literature Review
- 2018
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Other publication (other academic/artistic)abstract
- The objective is to systematically review the literature on economic evaluations of pharmacological treatments of dementia disorders. A systematic search of published economic evaluation studies in English was conducted using specified key words in relevant databased and websites. Data extracted included methods and empirical evidence (costs, effects, incremental cost-effectiveness ratio) and we assessed if the conclusions made in terms of cost-effectiveness were supported by the reported evidence. The included studies were also assessed for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Fourteen studies were included in this review. There was a considerable heterogeneity in methodological approaches, use of simulation models, target populations, study time frames, and perspectives as well as comparators used. Keeping these issues in mind, we find that Cholinesterase Inhibitors (ChEIs), and especially donepezil, are dominating no treatment (i.e. less costly and more effective) for mild to moderate AD patients. For moderate to severe AD patients memantine is cost-effective compared to memantine or ChEIs alone. However, the effect of these drugs on survival is yet not established, which could have a major impact on the cost-effectiveness of these drugs. Conclusion: Pharmaceutical treatments are cost-effective comparing to no treatment for dementia patients. However, more research is required on the long-term effectiveness of these drugs, especially on the effects of drugs on survival.
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| 5. |
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| 6. |
- Wattmo, Carina, et al.
(author)
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Cholinesterase inhibitor therapy does not affect time spent in nursing homes in patients with Alzheimer’s disease.
- 2016
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Conference paper (other academic/artistic)abstract
- Background: The time spent in nursing homes (NHs) by patients with Alzheimer’s disease (AD) might be influenced by many factors, e.g., sociodemographic and clinical characteristics, rate of disease progression, and concomitant disorders. Whether different aspects of cholinesterase inhibitor (ChEI) therapy (drug agent, dose, and duration) affect time spent in NHs has not been investigated. We studied the relationship between these potential predictors and time spent in NHs. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for the long-term assessment of ChEI therapy in a routine clinical setting. This presentation includes 220 deceased SATS participants clinically diagnosed with mild-to-moderate AD (Mini-Mental State Examination score, 10–26 at the start of ChEI treatment) who were admitted to NHs during the study. Cognitive and activities of daily living (ADL) capacities were evaluated at the baseline and semiannually over 3 years. The dates of nursing home placement (NHP) and death were recorded. Variables that determined time spent in NHs were analyzed using general linear models. Results: The mean (95% confidence interval) time spent in NHs was 4.06 (3.69–4.43) years: 2.78 (2.19–3.38) years for men vs 4.53 (4.09–4.96) years for women; P < 0.001. When considering the interaction effect of sex and living status, males living with a family member spent a shorter time in NHs (2.15 (1.48–2.83) years) vs the other groups: females living with family, 4.75 (4.00–5.50) years; males living alone, 4.00 (2.96–5.05) years; and females living alone, 4.41 (3.87–4.95) years; P < 0.001. The multivariate model showed that a shorter stay in NHs was independently related to being a man living with family, lower basic ADL at NHP, and more concomitant medications. Age, cognitive or instrumental ADL capacities at NHP, rates of decline in cognition or function, and ChEI type, dose, and treatment duration were not significant predictors. Conclusions: Women cared for their spouses with AD at home longer than did men. The situation of these female informal caregivers needs attention and possibly support. There was no indication that any aspects of ChEI therapy influenced the time spent in NHs.
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| 7. |
- Wattmo, Carina, et al.
(author)
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Levels of cerebrospinal fluid biomarkers total tau and phosphorylated tau do not predict survival time after diagnosis of Alzheimer’s disease – An 18-year follow-up.
- 2017
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Conference paper (other academic/artistic)abstract
- Background: The pathological process in Alzheimer’s disease (AD) probably starts decades before the onset of symptoms and the clinical AD diagnosis. In patients with AD, the level of cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ42) is usually lower, and the levels of total tau (T-tau) and phosphorylated tau (P-tau) higher than in healthy elderly people. However, the cutoffs differ between studies and the predictive values are too low to diagnose AD using only CSF biomarkers. Several previous reports have shown that the levels of T-tau and P-tau become pathological later in the course of AD compared with Aβ42, yet it is unclear if higher levels of tau shorten the individuals’ life expectancy after diagnosis. The current study aims to investigate whether pathological levels of T-tau and/or P-tau can predict survival in AD. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for the longitudinal assessment of cholinesterase inhibitor treatment in a routine clinical setting. This presentation includes all 151 participants clinically diagnosed with AD, who underwent a lumbar puncture. Patients were evaluated regarding cognitive and functional abilities at baseline (time of diagnosis) and semi-annually over 3 years. Socio-demographic characteristics, concomitant medications and the date of death were recorded. CSF was collected in polypropylene tubes, stored at −80 °C and analyzed after the clinical follow-up of the study was completed. The levels of T-tau, P-tau phosphorylated at Thr181 and Aβ42 were determined using xMAP technology. Pathological levels of CSF biomarkers were defined as: T-tau >100 ng/ml, P-tau >51 ng/ml and Aβ42 <209 ng/ml. Cox proportional hazards regression was used to determine the patient characteristics that affected mortality. Potential predictors were investigated, including sex, age at baseline, apolipoprotein E (APOE) e4 carrier status, years of education, the clinician’s estimated duration of AD, cognitive and functional abilities at baseline, the number of concomitant medications, and levels of CSF biomarkers. Results: The number and frequency of SATS participants with pathological CSF biomarkers were: T-tau, n=18 (12%); P-tau, n=14 (9%); and both T-tau and P-tau, n=46 (31%). All 151 individuals had pathological Aβ42. The group with normal T-tau and P-tau (n=73, 48%) had a higher education level, mean (95% confidence interval [CI]) 10.2 (9.5–10.8) vs. 9.1 (8.7–9.6) years, p=0.013; better cognitive ability at baseline, Mini-Mental State Examination, 22.8 (21.9–23.8) vs. 20.6 (19.5–21.6) points, p=0.002; and higher level of Aβ42 124 (118–129) vs. 117 (113–120) ng/ml, p=0.034, compared to patients with pathological T-tau and/or P-tau. No difference between the two groups was detected regarding the other aforementioned characteristics. After 18 years of follow-up, 139 of the 151 participants (92%) had died; their mean (95% CI) lifespan after diagnosis was 6.7 (6.2–7.3) years. No linear associations were found between survival time and Aβ42 (r = –0.005, p=0.957), T-tau (r = –0.127, p=0.135), or P-tau (r = –0.020, p=0.816). In a Kaplan–Meier analysis with pairwise Log-rank tests, the individuals with normal tau levels showed a longer life expectancy than those with pathological T-tau (p=0.044) and P-tau (p=0.025), but not if both tau biomarkers were pathological (p=0.439). However, using a one-way analysis of variance (ANOVA), the mean lifespan did not differ among the four groups: normal T-tau and P-tau, 7.0 (6.1–7.9) years; pathological T-tau, 5.6 (4.5–6.7) years; pathological P-tau, 5.9 (4.4–7.4) years; and both pathological T-tau and P-tau, 7.1 (6.1–8.1) years, p=0.276. The interaction effect of normal/pathological levels of tau with presence/absence of the APOE e4 allele did not affect the participants’ survival time in a Kaplan–Meier analysis, p=0.100, or in an ANOVA, p=0.451. In addition, no significant linear relationships were observed between life expectancy after AD diagnosis and any of the CSF biomarkers in the APOE e4 non-carrier or in the e4 carrier groups. Patients with the highest quartile and quintile of T-tau (>=126 and >=129 ng/ml) and P-tau (>=65 and >=70 ng/ml), respectively, were also examined; their lifespan did not differ from the other individuals. The actual continuous values of the CSF biomarkers or dichotomously coded normal/pathological, respectively, were not significant in Cox regression models adjusted for the above-mentioned predictors. Conclusion: Mortality in AD is complex and depends on many factors e.g., demographic and clinical. In this clinical-practice-based long-term study, almost half of the participants with AD had normal levels of tau. We found no clear results that the levels of T-tau and/or P-tau affect survival after diagnosis in AD. This observation does not support the theory that these patients have a more advanced disease. However, the individuals with pathological levels of tau had fewer years of education and worse cognitive status indicating a lower cognitive reserve capacity, which might influence life expectancy. These findings might be useful when considering new diagnostic criteria and when interpreting outcomes from future clinical trials of potentially disease-modifying AD therapies.
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| 8. |
- Wattmo, Carina, et al.
(author)
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The course and end-points of Alzheimer’s disease according to sociodemographics, apolipoprotein E genotype and cognitive ability.
- 2017
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Conference paper (other academic/artistic)abstract
- Background: The prognosis of Alzheimer’s disease (AD) might be influenced by many sociodemographic and clinical factors. Previous studies have investigated the main effects of critical predictors but few have analyzed potential interactions. We have studied the long-term cognitive outcome, nursing home placement (NHP) and mortality by interactions between factors in cholinesterase inhibitor (ChEI)-treated AD patients. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicenter study for longitudinal evaluation of ChEI treatment in clinical practice. This presentation includes 224 deceased SATS participants diagnosed with mild-to-moderate AD (Mini-Mental State Examination score (MMSE), 10–26 at the start of ChEI therapy, i.e., time of diagnosis) who were admitted to nursing homes (NHs) during the study. Cognitive abilities were evaluated at baseline and semiannually over 3 years. Dates of NHP and death were recorded. Results: Patients were divided into two groups by age at AD diagnosis, cut-off median 78 years. Younger females exhibited lower cognitive ability at NHP (mean MMSE score (95% confidence interval), 16.3 (14.9–17.7) points vs. 18.7 (17.6–19.7) points, p=0.018), and a longer time to NHP (22.1 (19.9–24.2) months vs. 15.6 (13.6–17.7) months, p<0.001), than older females. Females ≤77 years old had longer survival times in NHs, (5.4 (4.7–6.0) years), compared with the other groups: ≥78-year-old females, (4.1 (3.4–4.7) years); ≤77-year-old males, (2.8 (1.7–3.8) years); and ≥78-year-old males, (2.8 (2.0–3.5 years), p<0.001). Younger apolipoprotein E (APOE) e4-carriers demonstrated lower cognitive ability at NHP, (16.3 (14.9–17.7) points vs. 19.0 (17.9–20.1) points, p=0.021), longer time to NHP, (22.8 (20.8–24.8) months vs. 17.7 (15.4–19.9) months, p=0.006), longer survival time in NHs, (5.0 (4.4–5.7) years vs. 3.8 (3.2–4.5) years, p=0.030), and longer life-span from AD diagnosis, (6.9 (6.3–7.6) years vs. 5.3 (4.6–6.0) years, p=0.002), than older e4-carriers. Conclusions: In the ≤77-year-old group, a longer survival time in NHs (~5 years) and thus higher cost of care might be expected in females, mild AD or APOE e4-carriers. Younger patients with moderate AD showed remarkably low cognitive ability at NHP (mean MMSE score 12); these individuals might need increased support.
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| 9. |
- Wattmo, Carina, et al.
(author)
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Various outcomes of cholinesterase inhibitor treatment influence survival of patients with Alzheimer’s disease.
- 2015
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Conference paper (other academic/artistic)abstract
- Objectives: Various outcomes of cholinesterase inhibitor (ChEI) therapy have been observed in Alzheimer’s disease (AD). It is not clear whether the duration of treatment, type of ChEI, or dose affect mortality. We aimed to investigate the association between ChEI therapy and patient survival. Methods: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, multicentre study to evaluate long-term treatment with ChEIs in clinical practice. This study included 1021 outpatients with a clinical diagnosis of mild-to-moderate AD (Mini-Mental State Examination score, 10–26) at the start of ChEI treatment (shortly after diagnosis). The date of death of participants was recorded. Results: After up to 16 years of follow-up, 841 (82%) of the patients in the SATS had died. The mean ± standard deviation time from diagnosis of AD to death was 6.0 ± 2.9 years, and differed between individuals with varying durations of ChEI treatment in the study, from 7.2 ± 2.5 years (3-year completers) to 4.9 ± 2.9 years (<1 year) (P<0.001). Patients who received a higher mean dose of ChEIs during the study had a longer lifespan than those who received a lower dose (6.4 ± 2.9 vs 5.5 ± 2.8 years; P<0.001). The median cutoff values were donepezil 6.9 mg, rivastigmine 6.0 mg, and galantamine 15.0 mg. No difference in mortality between the types of ChEIs was found after adjusting for sex, age, and disease severity. Conclusions: Longer survival can be expected for AD patients who receive and tolerate higher ChEI doses and a longer duration of treatment.
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