Outcomes of Patients with COPD Treated with ICS/LABA Before and After Initiation of Single-Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI).

INTRODUCTION: Triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) has been shown to improve symptoms and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. This real-world study compared exacerbation rates and healthcare resource utilization (HCRU) before and after initiation of FF/UMEC/VI in patients with COPD previously treated with inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA). METHODS: This retrospective cohort study included commercial and Medicare Advantage with Part D administrative claims data from September 01, 2016, to March 31, 2020, of patients diagnosed with COPD. The index date was the date of the first FF/UMEC/VI claim (September 2017-March 2019). The 12 months prior to index (baseline) were used to assess patient characteristics and outcomes; the 12 months following index (follow-up) were used to assess study outcomes. All patients had ≥ 30 consecutive days' supply of any ICS/LABA dual therapy during the 12 months prior to FF/UMEC/VI initiation. Subgroup analyses included patients with ≥ 30 consecutive days' supply of budesonide/formoterol (BUD/FORM) during baseline. Analyses of patients with ≥ 1 COPD exacerbation during baseline were reported as well. RESULTS: The overall population included 1449 patients (mean age 70.75 years; 54.18% female), of whom 540 were patients in the BUD/FORM subgroup. Significantly fewer patients experienced any exacerbation during follow-up versus baseline (overall population 53.49% vs 62.59%; p < 0.001; BUD/FORM subgroup 55.00% vs 62.41%; p = 0.004). Effects on exacerbation reduction were more pronounced among patients with ≥ 1 exacerbation during baseline. Lower COPD-related HCRU was observed during the follow-up compared with baseline for both the overall population and the BUD/FORM subgroup. CONCLUSION: Patients with COPD treated with ICS/LABA during baseline, including patients specifically treated with BUD/FORM and those with a history of ≥ 1 exacerbation, had fewer COPD exacerbations and lower COPD-related HCRU after initiating FF/UMEC/VI.

Costs and Resource Use Associated with Community-Dwelling Patients with Alzheimer's Disease in Japan: Baseline Results from the Prospective Observational GERAS-J Study.

BACKGROUND: As the Japanese population ages, caring for people with Alzheimer's disease (AD) dementia is becoming a major socioeconomic issue. OBJECTIVE: To determine the contribution of patient and caregiver costs to total societal costs associated with AD dementia. METHODS: Baseline data was used from the longitudinal, observational GERAS-J study. Using the Mini-Mental State Examination (MMSE) score, patients routinely visiting memory clinics were stratified into three groups based on AD severity. Health care resource utilizationwas recorded using the Resource Utilization in Dementia questionnaire. Total monthly societal costs were estimated using Japan-specific unit costs of services and products (patient direct health care use, patient social care use, and informal caregiving time). Uncertainty around mean costs was estimated using bootstrapping methods. RESULTS: Overall, 553 community-dwelling patients withADdementia (28.3% mild[MMSE21-26], 37.8% moderate[MMSE 15-20], and 34.0% moderately severe/severe [MMSE < 14]) and their caregivers were enrolled. Patient characteristics were: mean age 80.3 years, 72.7% female, and 13.6% living alone. Caregiver characteristics were: mean age 62.1 years, 70.7% female, 78.8% living with patient, 49.0% child of patient, and 39.2% sole caregiver. Total monthly societal costs of AD dementia (Japanese yen) were: 158,454 (mild), 211,301 (moderate), and 294,224 (moderately severe/severe). Informal caregiving costs comprised over 50% of total costs. CONCLUSION: Baseline results of GERAS-J showed that total monthly societal costs associated with AD dementia increased with AD severity. Caregiver-related costs were the largest cost component. Interventions are needed to decrease informal costs and decrease caregiver burden.

Detection, diagnosis, and treatment of Alzheimer's disease dementia stratified by severity as reported by caregivers in Japan.

BACKGROUND: Dementia of Alzheimer's disease (AD) imposes burdens on patients, caregivers, and society. This cross-sectional study examined caregiver-reported history of disease onset and AD dementia to inform efforts promoting early disease detection and diagnosis. METHODS: An online survey collected self-reported cross-sectional data - demographic characteristics, diagnosis, treatment experiences, and other information on disease detection, diagnosis, and treatment - from caregivers of patients with AD dementia. These characteristics were examined as a function of AD dementia severity. RESULTS: Three hundred patients with AD dementia were trichotomized by long-term care insurance levels reported by caregivers: 12.3% (n=37) as low severity, 63.7% (n=191) as medium severity, and 24.0% (n=72) as high severity. The Short-Memory Questionnaire and patient dependency scores both varied significantly across severity groups. AD dementia symptoms were most frequently first detected by a caregiver (58.7%) or the patient's family (45.7%). However, in 13.7% of cases, symptoms were detected by a health care provider during a routine visit. Memory problems were the most frequent first symptoms (77.3%), followed by repetition (55.7%). Patients (73.7%) were taking symptomatic treatment such as acetylcholinesterase inhibitors or memantine. High-severity patients were older, had been diagnosed with AD dementia for a longer time, had more frequent reports of memory problems as the first symptoms detected, and required more hours of care per day, compared with low-severity patients. CONCLUSION: Caregivers and families play an integral role in the identification of AD dementia patients, with memory problems being common first symptoms noticed by caregivers that led to a diagnosis of AD dementia. These results provide novel insight into the detection, diagnosis, and treatment of AD dementia in Japan and how these factors differ across the spectrum of disease severity.

Alzheimer's disease severity and its association with patient and caregiver quality of life in Japan: results of a community-based survey.

BACKGROUND: Alzheimer's disease (AD) dementia, a progressive neurodegenerative disease, exerts significant burden upon patients, caregivers, and healthcare systems globally. The current study investigated the associations between AD dementia patient disease severity and health-related quality of life (HRQoL) of both patients (proxy report) and their caregivers living in Japan, as well as caregiving-related comorbidities such as depression. METHODS: This cross-sectional study used self-reported data from caregivers of people diagnosed with AD dementia by a healthcare provider in Japan. Caregivers were identified via online panels and invited to participate in an online survey between 2014 and 2015. Caregivers completed survey items for themselves, in addition to providing proxy measures for patients with AD dementia for whom they were caring. Patient and caregiver HRQoL was measured using the EuroQoL 5-Dimension (EQ-5D). Additional outcomes for caregivers of AD dementia patients included the Patient Health Questionnaire (PHQ-9) of depressive symptomology, as well as comorbidities experienced since initiating caregiving for their AD dementia patients. These outcomes were examined as a function of AD dementia severity, as measured by long-term care insurance (LTCI) categories. Bivariate analyses between LTCI and outcomes were conducted using independent t-tests and chi-square tests. Multivariable analyses, controlling for potential confounders, were conducted using generalized linear models (GLMs) specifying a normal distribution. RESULTS: Across 300 caregiver respondents, multivariable results revealed that increasing AD dementia severity was significantly associated with poorer patient and caregiver EQ-5D scores and a high proportion of caregivers (30.0%) reported PHQ-9 scores indicative of major depressive disorder (MDD). The most frequent comorbidities experienced after becoming caregivers of AD dementia patients included hypertension (12.7%) and insomnia (11.0%). Depression and other comorbidities did not differ significantly by patient severity. CONCLUSIONS: The current study provides unique insight into the specific degree of incremental burden associated with increasing AD dementia severity among patients and caregivers alike. Importantly, greater disease severity was associated with poorer quality of life among both patients and caregivers. These results suggest that earlier detection and treatment of AD dementia may provide an opportunity to reduce the burden of disease for patients, caregivers, and society at large.

Representativeness of European clinical trial populations in mild Alzheimer's disease dementia: a comparison of 18-month outcomes with real-world data from the GERAS observational study.

BACKGROUND: Comparison of disease progression between placebo-group patients from randomised controlled trials (RCTs) and real-world patients can aid in assessing the generalisability of RCT outcomes. This analysis compared outcomes between community-dwelling patients with mild Alzheimer's disease (AD) dementia from two RCTs (pooled European (EU) data from EXPEDITION and EXPEDITION 2) and similar patients from the EU GERAS observational study. METHODS: Data from placebo-group patients with mild AD dementia from the RCTs (EU countries only) were compared with data from GERAS patients with mild AD dementia. Between-group differences for changes over 18 months were analysed for cognition, functioning, neuropsychiatric symptoms, health-related quality of life (HRQoL) and caregiver time using propensity score-adjusted models. A sensitivity analysis compared EU/North American (EU/NA) EXPEDITION patients with GERAS patients. RESULTS: EU EXPEDITION patients (n = 168) were younger than GERAS patients (n = 566) (mean (standard deviation, SD) age 71.9 (7.4) versus 77.3 (6.9) years; p < 0.001) and were more likely to use AD treatment (95% versus 84%; p < 0.001). Cognitive performance was similar at baseline in both populations, although GERAS patients showed greater functional impairment (p = 0.005) and lower HRQoL (p < 0.05). At 18 months, no statistically significant differences between EXPEDITION (n = 133) and GERAS (n = 417) patients were observed for changes in cognitive, functional, neuropsychiatric and HRQoL outcomes. Least squares mean (95% confidence interval) change in caregiver time (hours/month) spent on instrumental activities of daily living (iADL; 29.22 (19.16, 39.27) versus 3.20 (-11.89, 18.28), p = 0.001) and supervision (66.59 (47.49, 85.69) versus 3.04 (-25.39, 31.48), p < 0.001) showed greater increases in GERAS than EXPEDITION. In the sensitivity analysis, changes in neuropsychiatric and HRQoL scores and caregiver time spent on basic ADL were also significantly greater in GERAS than in EU/NA EXPEDITION patients. CONCLUSIONS: Patients with mild AD dementia participating in the EU EXPEDITION RCTs and the GERAS observational study showed a similar decline in cognitive, functional and neuropsychiatric symptoms over 18 months, whereas changes in caregiver time measures were significantly greater in GERAS. Results indicate the importance of using similar regions when comparing real-world and RCT data. TRIAL REGISTRATION: ClinicalTrials.gov NCT00905372 EXPEDITION. Registered 18 May 2009. ClinicalTrials.gov NCT00904683 EXPEDITION 2. Registered 18 May 2009.

Patient Characteristics and Outcomes Associated with Receiving an Earlier Versus Later Diagnosis of Probable Alzheimer's Disease.

BACKGROUND: Effectiveness of Alzheimer's disease (AD) treatments may depend critically on the timeliness of intervention. OBJECTIVE: To compare characteristics and outcomes of patients diagnosed with probable AD (prAD) based on time elapsed from first onset of cognitive decline. METHODS: Patients with ≥1 prAD diagnosis and ≥1 follow-up visit were selected from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS; 9/2005-6/2015) and stratified based on the time between the perceived onset of cognitive decline at baseline and first prAD diagnosis (i.e., earlier versus later diagnosis). Characteristics at baseline and prAD diagnosis, clinically meaningful progression, and medication use following prAD diagnosis were compared. RESULTS: Median time from perceived onset of cognitive decline to prAD diagnosis was 4.5 years (earlier diagnosis: ≤3.46; later diagnosis: >5.71). Earlier-diagnosed patients (n = 1,476) were younger at baseline (74.3 versus 76.3 years) and had better cognitive and functional scores than later-diagnosed patients (n = 1,474). At first prAD diagnosis, earlier-diagnosed patients had lower mean global Clinical Dementia Rating (CDR) score (0.8 versus 1.1), higher mean Mini-Mental State Examination (MMSE) (22.6 versus 20.0), and lower mean Functional Activities Questionnaire (11.6 versus 17.3). Earlier- and later-diagnosed patients experienced similar time to a decrease of ≥3 points in MMSE (median 23.2 versus 23.1 months, p = 0.83), but earlier-diagnosed patients had longer time to a CDR score of ≥2 points, and longer times to initiation of AD medication and antipsychotic agents (all p < 0.01). CONCLUSION: Earlier prAD diagnosis in NACC data is associated with higher cognitive function and lower functional impairment at diagnosis.

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes.

BACKGROUND/AIMS: We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. METHODS: Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. RESULTS: Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. CONCLUSION: Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia.

A Claims-Based Examination of Health Care Costs Among Spouses of Patients With Alzheimer's Disease.

BACKGROUND: Spouses of Alzheimer's disease patients (AD spouses) may experience substantial health effects associated with their partner's chronic cognitive and behavioral dysfunction. Studies examining associations between the medical experiences of AD spouses in the period before and after their partner's AD diagnosis are limited, particularly those which measure health care resource use and cost. METHODS: AD patients were identified through multiple Medicare claims containing an AD diagnostic code. Their spouses were identified through special coding in the Medicare eligibility records. The AD spouses were matched demographically to the spouses of Medicare beneficiaries without a history of AD. Longitudinal and annual cross-sectional Medicare cost comparisons utilized log-transformed linear regression. The longitudinal period of observation began 12 months before the AD patient's initial claim listing AD and continued for up to 38 months afterwards. RESULTS: The study identified 16,322 AD spouses. Total per person costs were 24% higher in AD spouses than in the controls ($694/month vs $561/month). AD spouses' excess costs began 3 months before their partners' AD diagnoses and continued for ≥30 months. Being an AD spouse predicted 29% higher Medicare costs after adjustment for chronic health status (P < .001). Increasing AD patient care complexity had a substantial impact on AD spouse Medicare costs (P < .001). CONCLUSIONS: This study documents a link between the health status of AD spouses and AD patients. Additional research is required to elicit the mechanism behind the association between AD spouse and AD patient diagnosis.

Functional limitations and health care resource utilization for individuals with cognitive impairment without dementia: Findings from a United States population-based survey.

INTRODUCTION: Little is known about functional limitations and health care resource utilization of people with cognitive impairment with no dementia (CIND). METHODS: Respondents with stable or progressive cognitive impairment (CI) after the first (index) indication of CIND in 2000-2010 were identified from the Health and Retirement Study (HRS). Respondents never exhibiting CI were identified as potential controls. Propensity score-based optimal matching was used to adjust for differences in demographics and history of stroke. Differences between cohorts were assessed accounting for HRS survey design. RESULTS: After matching, CIND respondents had more functional limitations (difficulty with ≥1 activities of daily living: 24% vs. 15%; ≥1 instrumental activities of daily living: 20% vs. 11%) and hospital stays (37% vs. 27%) than respondents with no CI (all P < .001). Seventy five percent of CIND respondents developed dementia in the observable follow-up (median time: ∼6 years). DISCUSSION: Even before dementia onset, CI is associated with increased likelihood of functional limitations and greater health care resource use.

Assessing quality of life in Alzheimer's disease: Implications for clinical trials.

INTRODUCTION: Characterization of the quality of life (QOL) in Alzheimer's disease (AD) scale within the context of a clinical trial may inform its applicability in future trials. METHODS: Using data from 1322 patients enrolled in two phase-III studies (EXPEDITION 1 [NCT00905372] and 2 [NCT00904683]) of intravenous solanezumab in outpatients with mild AD dementia, correlations between patient- and caregiver-assessed QOL and between QOL and clinical outcome measures were examined. Longitudinal effects of solanezumab over 80 weeks were explored, controlling for patient and caregiver baseline characteristics. RESULTS: Caregivers rated patients' QOL worse than did patients themselves. Patients' QOL was correlated, albeit modestly, with clinical/health measures. Patients' QOL changed minimally over 80 weeks, although a treatment effect of solanezumab on QOL was detected. DISCUSSION: Further investigations are needed to determine the optimal measures with which to quantify and qualify QOL of patients with mild AD.

The influence of caregivers and behavioral and psychological symptoms on nursing home placement of persons with Alzheimer's disease: A matched case-control study.

OBJECTIVES: Behavioral and psychological symptoms of dementia in individuals with Alzheimer's disease and caregiver characteristics may influence the decision to provide care at home or in a nursing home, though few studies examine this association near the actual time of nursing home placement. Using a matched case-control design, this study investigates the association between (1) total Neuropsychiatric Inventory score, (2) the Neuropsychiatric Inventory-4 (an agitation/aggression subscale), and (3) individual domains of the Neuropsychiatric Inventory and nursing home placement. METHODS: Data from the South Carolina Alzheimer's disease Registry provides an opportunity to expand the literature by looking at cases at the time of nursing home care eligibility/placement and allowing for propensity-score-matched controls. Cases (n = 352) entered a nursing home within 6 months of study initiation; controls (n = 289) remained in the community. Registry data were combined with caregiver survey data, including the Neuropsychiatric Inventory. Conditional logistic regression was applied. RESULTS: A 10% increase in the Neuropsychiatric Inventory score implied a 30% increase in odds of nursing home admission (odds ratio: 1.30; 95% confidence interval: 1.14-1.50), having married or male caregivers predicted nursing home placement. Cases versus controls were significantly more likely to have behavioral and psychological symptoms of dementia related to agitation/aggression 1 month prior to nursing home admission. CONCLUSION: Interventions targeting behavioral and psychological symptoms of dementia without available effective interventions in individuals with Alzheimer's disease and caregiver support services are necessary to prevent or delay nursing home admission.

How to deal with missing longitudinal data in cost of illness analysis in Alzheimer's disease-suggestions from the GERAS observational study.

BACKGROUND: Missing data are a common problem in prospective studies with a long follow-up, and the volume, pattern and reasons for missing data may be relevant when estimating the cost of illness. We aimed to evaluate the effects of different methods for dealing with missing longitudinal cost data and for costing caregiver time on total societal costs in Alzheimer's disease (AD). METHODS: GERAS is an 18-month observational study of costs associated with AD. Total societal costs included patient health and social care costs, and caregiver health and informal care costs. Missing data were classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Simulation datasets were generated from baseline data with 10-40 % missing total cost data for each missing data mechanism. Datasets were also simulated to reflect the missing cost data pattern at 18 months using MAR and MNAR assumptions. Naïve and multiple imputation (MI) methods were applied to each dataset and results compared with complete GERAS 18-month cost data. Opportunity and replacement cost approaches were used for caregiver time, which was costed with and without supervision included and with time for working caregivers only being costed. RESULTS: Total costs were available for 99.4 % of 1497 patients at baseline. For MCAR datasets, naïve methods performed as well as MI methods. For MAR, MI methods performed better than naïve methods. All imputation approaches were poor for MNAR data. For all approaches, percentage bias increased with missing data volume. For datasets reflecting 18-month patterns, a combination of imputation methods provided more accurate cost estimates (e.g. bias: -1 % vs -6 % for single MI method), although different approaches to costing caregiver time had a greater impact on estimated costs (29-43 % increase over base case estimate). CONCLUSIONS: Methods used to impute missing cost data in AD will impact on accuracy of cost estimates although varying approaches to costing informal caregiver time has the greatest impact on total costs. Tailoring imputation methods to the reason for missing data will further our understanding of the best analytical approach for studies involving cost outcomes.

Assessing the economic burden of Alzheimer's disease patients first diagnosed by specialists.

BACKGROUND: It is not known if there is a differential impact on Alzheimer's disease (AD) diagnosis and outcomes if/when patients are diagnosed with cognitive decline by specialists versus non-specialists. This study examined the cost trajectories of Medicare beneficiaries initially diagnosed by specialists compared to similar patients who received their diagnosis in primary care settings. METHODS: Patients with ≥2 claims for AD were selected from de-identified administrative claims data for US Medicare beneficiaries (5 % random sample). The earliest observed diagnosis of cognitive decline served as the index date. Patients were required to have continuous Medicare coverage for ≥12 months pre-index (baseline) and ≥12 months following the first AD diagnosis, allowing for up to 3 years from index to AD diagnosis. Time from index date to AD diagnosis was compared between those diagnosed by specialists (i.e., neurologist, psychiatrist, or geriatrician) versus non-specialists using Kaplan-Meier analyses with log-rank tests. Patient demographics, Charlson Comorbidity Index (CCI) during baseline, and annual all-cause medical costs (reimbursed by Medicare) in baseline and follow-up periods were compared across propensity-score matched cohorts. RESULTS: Patients first diagnosed with cognitive decline by specialists (n = 2593) were younger (78.8 versus 80.8 years old), more likely to be male (40 % versus 34 %), and had higher CCI scores and higher medical costs at baseline than those diagnosed by non-specialists (n = 13,961). However, patients diagnosed by specialists had a significantly shorter time to AD diagnosis, both before and after matching (mean [after matching]: 3.5 versus 4.6 months, p < 0.0001). In addition, patients diagnosed by specialists had significantly lower average total all-cause medical costs in the first 12 months after their index date, a finding that persisted after matching ($19,824 versus $25,863, p < 0.0001). Total per-patient annual medical costs were similar for the two groups starting in the second year post-index. CONCLUSIONS: Before and after matching, patients diagnosed by a specialist had a shorter time to AD diagnosis and incurred lower costs in the year following the initial cognitive decline diagnosis. Differences in costs converged during subsequent years. This suggests that seeking care from specialists may yield more timely diagnosis, appropriate care and reduced costs among those with cognitive decline.

Impact of caring for persons with Alzheimer's disease or dementia on caregivers' health outcomes: findings from a community based survey in Japan.

BACKGROUND: This study assessed how family caregivers for patients with Alzheimer's disease (AD) or dementia in Japan differed from non-caregivers in characteristics and health outcomes (i.e., comorbidities, health-related quality of life [HRQoL], productivity, and resource use). Caregivers were hypothesized to experience significantly poorer outcomes than non-caregivers. METHODS: Data were combined from the 2012 and 2013 National Health and Wellness Survey in Japan (n = 60000). Caregivers for adult relatives with AD or dementia were compared with non-caregivers on: comorbidities (including Patient Health Questionnaire (PHQ-9) cutoff scores suggesting presence/absence of major depressive disorder (MDD)), Work Productivity and Activity Impairment (WPAI), SF-36v2-based HRQoL, and healthcare resource utilization. Sociodemographic characteristics, health characteristics and behaviors, and Charlson comorbidity index (CCI) scores were compared across groups. Propensity matching, based on scores generated from a logistic regression predicting caregiving, was used to match caregivers with non-caregivers with similar likelihood of being caregivers. Bivariate comparisons across matched groups served to estimate outcomes differences due to caregiving. RESULTS: Among 55060 respondents, compared with non-caregivers (n = 53758), caregivers (n = 1302) were older (52.6 vs. 47.5 years), more frequently female (53 % vs. 49 %), married/partnered, frequent alcohol drinkers, current smokers, exercisers, and not employed, and they averaged higher CCI scores (0.37 vs. 0.14), all p < 0.05. Propensity scores incorporated sex, age, body mass index (BMI), exercise, alcohol, smoking, marital status, CCI, insured status, education, employment, income, and children in household. A greedy matching algorithm produced 1297 exact matches, excluding 5 non-matched caregivers. Health utilities scores were significantly lower among caregivers (0.724) vs. non-caregivers (0.764), as were SF-36v2 Physical and Mental Component Summary scores. Caregivers vs. non-caregivers had significantly higher absenteeism, presenteeism-related impairment, overall work impairment (25.8 % vs. 20.4 %, respectively), and activity impairment (25.4 % vs. 21.8 %), more emergency room and traditional provider visits (7.70 vs. 5.35) in the past six months, and more frequent MDD (14 % vs. 9 %), depression, insomnia, anxiety, and pain. CONCLUSIONS: Those providing care for patients with AD or dementia in Japan experienced significantly poorer HRQoL and greater comorbid risk, productivity impairment, and resource use. These findings inform the need for greater support for caregivers and their patients.

Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer's disease.

BACKGROUND: The burden on caregivers of patients with Alzheimer's disease (AD) is associated with the patient's functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed. METHODS: Baseline data from the GERAS observational study of patients with AD and their caregivers (both n = 1495) in France, Germany and the UK were analyzed. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Caregiver time on activities of daily living (ADL: basic ADL; instrumental ADL, iADL) and supervision (hours/month), and caregiver and patient HCRU (outpatient visits, emergency room visits, nights hospitalized) were assessed using the Resource Utilization in Dementia instrument for the month before the baseline visit. Regression analyses were adjusted for relevant covariates. Time on supervision and basic ADL was analyzed using zero-inflated negative binomial regression. RESULTS: Caregivers of patients with diabetes (n = 188) were younger and more likely to be female (both p < 0.05), compared with caregivers of patients without diabetes (n = 1307). Analyses showed caregivers of patients with diabetes spent significantly more time on iADL (+16 %; p = 0.03; increases were also observed for basic ADL and total caregiver time but did not reach statistical significance) and had a trend towards increased ZBI score. Patients with diabetes had a 63 % increase in the odds of requiring supervision versus those without diabetes (p = 0.01). Caregiver and patient HCRU did not differ according to patient diabetes. Caregivers with diabetes (n = 127) did not differ from those without diabetes (n = 1367) regarding burden/time, but caregivers with diabetes had a 91 % increase in the odds of having outpatient visits (p = 0.01). CONCLUSIONS: This cross-sectional analysis found caregiver time on iADL and supervision was higher for caregivers of patients with AD and diabetes versus without diabetes, while HCRU was unaffected by patient diabetes. Longitudinal analyses assessing change in caregiver burden over time by patient diabetes status may help clarify the cumulative impact of diabetes and AD dementia on caregiver burden.

Caregiving for patients with Alzheimer's disease or dementia and its association with psychiatric and clinical comorbidities and other health outcomes in Brazil.

OBJECTIVES: Individuals with dementia due to Alzheimer's disease often receive care from family members who experience associated burden. This study provides the first broad, population-based account of caregiving-related health outcome burden in Brazil. METHODS: Data were analyzed from the 2012 National Health and Wellness Survey in Brazil (n = 12,000), an Internet-based survey of adults (aged 18+ years), using stratified sampling by sex and age to ensure demographic representation of Brazil's adult population. Caregivers of individuals with Alzheimer's disease or dementia were compared with non-caregivers on comorbidities, productivity impairment, health-related quality of life, resource utilization, sociodemographic/health characteristics and behaviors, and Charlson comorbidity index scores. Regression models assessed outcomes associated with caregiving, adjusting for potential confounds. RESULTS: Among 10,853 respondents, caregivers' (n = 209) average age was 42.1 years, 53% were female, and 52% were married/living with a partner. Caregivers versus non-caregivers (n = 10,644) were more frequently obese, smokers, insured, employed, college-educated, and wealthier and had higher Charlson comorbidity index, all p < 0.05. Adjusting for covariates, caregiving was associated with significantly increased risk of depressive symptoms (odds ratio [OR] = 2.008), major depressive disorder (OR = 1.483), anxiety (OR = 1.714), insomnia (OR = 1.644), hypertension (OR = 1.584), pain (OR = 1.704), and diabetes (OR = 2.103), all p < 0.015. Caregiving was also associated with lower health utilities (-0.024 points) and mental health status (-1.70 points), higher rates of presenteeism-related impairment (32.7% greater) and overall work impairment (35.9% greater), and higher traditional provider visit rates (28.7% greater), all p < 0.035. CONCLUSIONS: Caregiver status was found to be a factor associated with worse health outcomes and psychiatric and clinical disorders.

Cognitive and Functional Decline in Patients With Mild Alzheimer Dementia With or Without Comorbid Diabetes.

PURPOSE: Although diabetes is recognized as a risk factor for the development of cognitive impairment and for accelerated progression to Alzheimer disease (AD), it is unclear whether patients with diabetes who have already progressed to AD have a different rate of cognitive and functional decline compared with that in those without diabetes. This post hoc exploratory analysis compared cognitive and functional decline over an 18-month period in patients with mild AD dementia with and without comorbid diabetes. Decline in quality of life was assessed as a secondary objective. METHODS: In a post hoc exploratory analysis, we analyzed data from the placebo groups of three 18-month, randomized, placebo-controlled trials of solanezumab and semagacestat in patients with AD. Data from patients with mild AD dementia (Mini-Mental State Examination [MMSE] score, 20-26) and comorbid diabetes at baseline were compared with data from patients with mild AD dementia without diabetes at baseline. Cognition was assessed using the 14-item AD Assessment Scale-Cognitive Subscale (ADAS-Cog14) and the MMSE. Functioning was assessed with the AD Cooperative Study-Activities of Daily Living Inventory (instrumental subset) (ADCS-iADL). Quality of life was assessed using the European Quality of Life-5 Dimensions scale, proxy version (proxy utility score and visual analog scale score), and the Quality of Life in AD scale, self-report and proxy (caregiver) versions. Group comparisons of changes from baseline to 18 months in cognitive, functional, and quality-of-life measures employed a repeated-measures model adjusted for propensity score, study, baseline cognition score (functional or quality of life), age, sex, level of education, genotype of the apolipoprotein E gene, and concurrent use of an acetylcholinesterase inhibitor or memantine. FINDINGS: At baseline, patients with mild AD dementia with and without diabetes did not significantly differ on the cognitive measures, but those without diabetes were functioning at a significantly higher level. At 18 months, compared with patients without diabetes, those with diabetes showed a numerically but statistically nonsignificantly lesser cognitive decline (least squares mean between-group differences: ADAS-Cog14 score, 1.61 [P = 0.21]; MMSE score, -0.40 [P = 0.49]) and a statistically significantly lesser functional decline (least squares mean between-group difference in ADCS-iADL score, -3.07; P = 0.01). The 2 groups did not differ on declines in the quality-of-life measures. IMPLICATIONS: The present findings suggest that diabetes may influence the rate of functional decline among patients with mild AD dementia. These results require replication in studies that address the limitations of the present post hoc exploratory analysis and that explore the potential causes of the observed differences.

Methodological challenges in assessing the impact of comorbidities on costs in Alzheimer's disease clinical trials.

BACKGROUND: Alzheimer's disease (AD) is associated with considerable costs and has a significant impact on health and social care systems. OBJECTIVE: This study assessed whether baseline comorbidities present in 2,594 patients with AD participating in two semagacestat randomized placebo-controlled trials (RCTs) would significantly impact overall costs. METHODS: Resource utilization was captured using the Resource Utilization in Dementia Scale-Lite. Comorbidities and concomitant medications were tabulated via patient and caregiver reports. Only baseline data were analyzed. Direct and indirect costs per month were calculated per patient. The relationship between cost and explanatory variables was explored in a regression model. RESULTS: The baseline monthly cost of care in this RCT population was £1,147 ± 2,483, with informal care costs accounting for 75% of costs. Gender, age, and functional status were significant predictors of costs (p ≤ 0.0001). The cost ratio was not impacted when the number of comorbidities was added to the model (cost ratio = 0.95; 95% CI 0.91-0.99) or when combined with the number of concomitant medications (cost ratio = 0.97; 95% CI 0.95-1.00). Inconsistent findings related to the impact of individual comorbidities on costs were noted in sensitivity analyses. CONCLUSIONS: The number of comorbidities, alone or when combined with concomitant medications, did not impact baseline costs of care, perhaps because RCTs often enroll less severely ill and more medically stable patients. However, higher costs were consistently associated with greater functional impairment similar to non-RCT databases. Supplemental sources (e.g., claims databases) are likely needed to better estimate the effects of disease and treatment on costs of illness captured in RCTs for AD.

Assessing cognition and function in Alzheimer's disease clinical trials: do we have the right tools?

Several lines of evidence from Alzheimer's disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging-Alzheimer's Association revised criteria for AD provided a framework for this new thinking. As a result of this growing understanding, several research efforts have launched or will be launching large secondary prevention trials in AD. These and other efforts have clearly demonstrated a need for better measures of cognitive and functional change in people with the earliest changes associated with AD. Recent draft guidance from the US Food and Drug Administration further elevated the importance of cognitive and functional assessments in early stage clinical trials by proposing that even in the pre-symptomatic stages of the disease, approval will be contingent on demonstrating clinical meaningfulness. The Alzheimer's Association's Research Roundtable addressed these issues at its fall meeting October 28-29, 2013, in Washington, D.C. The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD.

Using U.S. Medicare records to evaluate the indirect health effects on spouses: a case study in Alzheimer's disease patients.

BACKGROUND: The burden experienced by spouses of patients with Alzheimer's disease (AD) may have negative consequences for their physical health. We describe here a method for analyzing United States Medicare records to determine the changes in health service use and costs experienced by spouses after their marital partner receives an AD diagnosis. METHODS: We initially identified all beneficiaries in the 2001-2005 Medicare 5% sample who had multiple claims listing the ICD-9 diagnostic code for AD, 331.0. The 5% sample includes spouses who share a Medicare account with their marital partners because they lack a sufficient work history for full eligibility on their own. A matched cohort study assessed incremental health costs in the spouses of AD patients versus a control group of spouses of non-AD patients. Longitudinal and cross-sectional analyses tracked the impact of a patient's AD diagnosis on his or her spouse's healthcare costs. RESULTS: Our method located 54,593 AD patients of whom 11.5% had spouses identifiable via a shared Medicare account. AD diagnosis in one member of a couple was associated with significantly higher monthly Medicare payments for the other member's healthcare. The spouses' elevated costs commenced 2 to 3 months before their partners' AD diagnosis and persisted over the follow-up period. After 31 months, the cumulative additional Medicare reimbursements totaled a mean $4,600 in the spouses of AD patients. This excess was significant even after accounting for differences in baseline health status between the cohorts. CONCLUSION: The study methodology provides a framework for comprehensively evaluating medical costs of both chronically ill patients and their spouses. This method also provides monthly data, which makes possible a longitudinal evaluation of the cost effects of specific health events. The observed correlations provide a coherent demonstration of the interdependence between AD patients' and spouses' health. Future research should examine caregiving burden and other possible factors contributing to the AD spouses' health outcomes. It should also extend the method presented here to evaluations of other chronic diseases of the elderly.