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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.

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

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.

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.

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

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

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

OBJECTIVE: Neuropsychiatric symptoms, including agitation and aggression (A/A), are highly prevalent in Alzheimer's disease (AD) and are associated with increased disability, functional impairment, caregiver distress, and institutionalization. Previous psychometric work suggests that individual items of agitation, irritability, disinhibition, and aberrant motor behavior from the Neuropsychiatric Inventory (NPI) may be a valid measure of A/A in AD. We provide additional confirmation of this subscale, as well as preliminary validation of it as a measure of A/A (the NPI-4-A/A). METHODS: The sample included 641 individuals identified from the South Carolina Alzheimer's Disease Registry and assessed to be at a nursing home level of care. Demographic and medical data were extracted from the Registry, and phone interviews were conducted with caregivers to collect additional information not included in the Registry. The primary statistical analysis was confirmatory factor analysis of the NPI-12 factor structure. RESULTS: The standardized root mean residual and root mean square error of approximation (90% CI) values of 0.060 and 0.043 (0.030, 0.057), respectively suggest adequate model fit of the data, whereas the Tucker-Lewis index estimate of 0.779 is below the criteria for adequate model fit. All but two normalized residuals (NR) suggested adequate model fit of the data (|NR| Language: en

This study examined in detail patterns of cholinesterase inhibitors (ChEIs) and memantine use and explored the relationship between patient characteristics and such use. Patients with probable Alzheimer disease AD (n = 201) were recruited from the Predictors Study in 3 academic AD centers and followed from early disease stages for up to 6 years. Random effects logistic regressions were used to examine effects of patient characteristics on ChEIs/memantine use over time. Independent variables included measures of function, cognition, comorbidities, the presence of extrapyramidal signs, psychotic symptoms, age, sex, and patient’s living situation at each interval. Control variables included assessment interval, year of study entry, and site. During a 6-year study period, rate of ChEIs use decreased (80.6% to 73.0%) whereas memantine use increased (2.0% to 45.9%). Random effects logistic regression analyses showed that ChEI use was associated with better function, no psychotic symptoms, and younger age. Memantine use was associated with better function, poorer cognition, living at home, later assessment interval, and later year of study entry. Results suggest that high rate of ChEI use and increasing memantine use over time are consistent with current practice guidelines of initiation of ChEIs in mild-to-moderate AD patients and initiation of memantine in moderate-to-severe patients.

OBJECTIVES To evaluate the sensitivity and specificity of the Mini-Mental State Examination (MMSE) in identifying dementia in the oldest-old when stratified by age and education.

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.

This study aimed to describe the baseline characteristics of informal carers of community-living Alzheimer's disease (AD) patients by AD severity group and to identify factors associated with two measures of caregiver burden.GERAS is a prospective observational study in France, Germany, and the UK, designed to assess costs and resource use associated with AD, for patients and their caregivers, stratified by disease severity.1497 community-dwelling AD patients and their primary caregivers.Subjective caregiver burden assessed using the Zarit Burden Interview [ZBI] and time spent supervising patients (an objective measure of burden recorded using the Resource Utilization in Dementia instrument) during the month before the baseline visit were recorded. Separate multiple linear regression analyses using ZBI total score and caregiver supervision time as dependent variables were performed to identify patient and caregiver factors independently associated with caregiver burden.Increasing AD severity was associated with both subjective caregiver burden (ZBI total score) and overall caregiver time, which includes supervision time (both p0.001, ANOVA). Better patient functioning (on instrumental activities of daily living) was independently associated with both a lower ZBI total score and less supervision time, whereas higher levels of caregiver distress due to patient behavior were associated with greater caregiver burden. Other factors independently associated with an increased ZBI total score included younger caregiver age, caregiver self-reported depression, caring for a male patient, and longer time since AD diagnosis. Caregivers living with the patient, being a male caregiver, patient living in a rural location, higher patient behavioral problem subdomain scores for apathy and psychosis, more patient emergency room visits, not receiving food delivery and receiving financial support for caregiving were all associated with greater caregiver supervision time.Our results show that subjective caregiver burden and caregiver time are influenced by different factors, reinforcing the need to consider both aspects of caregiving when trying to minimize the burden of AD. However, interventions that minimize caregiver distress and improve patient functioning may impact on both subjective and objective burden.

Background Advances in screening and treatment are needed to mitigate increasing prevalence of dementia due to Alzheimer's disease (DAT). Current proposals to revise Alzheimer's disease (AD) diagnostic criteria incorporate diagnostic biomarkers. Such revisions would allow identification of persons with AD pathology before the onset of dementia. The population-level impact of screening for preclinical AD and treating with a disease-modifying agent is important when evaluating new biomarkers and medications. Methods A published computer simulation model assigned AD-related event times, such that delays in disease progression due to therapy effectiveness can be estimated for a preclinical AD cohort. Attributes such as screening sensitivity/specificity, treatment efficacy, age at first screening, and rescreening intervals were varied. Outcomes included incident mild cognitive impairment (MCI-AD), incident DAT, and number of patients recommended for treatment. Results One-time screening at age 65 years, 50% efficacy, and literature-based proxy persistence rates yielded 12.4% incidence of MCI-AD and 0.9% decrease in DAT incidence from base case of no screening/treatment. Modest reductions in incident MCI-AD and DAT were observed with more sensitive testing. Reducing specificity yielded greater reductions in MCI-AD and DAT cases, albeit by treating more patients. Probabilistic sensitivity analysis predicted that for a cohort of patients aged 65 years, the number that needed to be treated to avoid one AD case was 11.6 (range: 5.7–104). Conclusion The reduction in MCI-AD and DAT depends on initial screening age, screening frequency, and specificity. When considering population-level impact of screening–treatment, the effect of these parameters on incidence would need to be weighed against the number of individuals screened and treated.

This study explores the longitudinal relationship between patient characteristics and use of 4 drug classes (antihypertensives, antidepressants, antipsychotics, and hormones) that showed significant changes in use rates over time in patients with Alzheimer disease. Patient/caregiver-reported prescription medication usage was categorized by drug class for 201 patients from the Predictors Study. Patient characteristics included use of cholinesterase inhibitors and/or memantine, function, cognition, living situation, baseline age, and sex. Assessment interval, year of study entry, and site were controlled for. Before adjusting for covariates, useage increased for antihypertensives (47.8% to 62.2%), antipsychotics (3.5% to 27.0%), and antidepressants (32.3% to 40.5%); use of hormones decreased (19.4% to 5.4%). After controlling for patient characteristics, effects of time on the use of antidepressants were no longer significant. Antihypertensive use was associated with poorer functioning, concurrent use of memantine, and older age. Antipsychotic use was associated with poorer functioning and poorer cognition. Antidepressant use was associated with younger age, poorer functioning, and concurrent use of cholinesterase inhibitors and memantine. Hormone use was associated with being female and younger age. Findings suggest accurate modeling of the Alzheimer disease treatment paradigm for certain subgroups of patients should include antihypertensives and antipsychotics in addition to cholinesterase inhibitors and memantine.

An increasing number of individuals in our population are surviving to over 90 years and a subset is at risk for developing dementia. However, senile plaque and neurofibrillary tangle pathology do not consistently differentiate individuals with and without dementia. Synaptic protein loss is a feature of aging and dementia and may dissociate 90+ individuals with and without dementia. Synaptophysin (SYN), postsynaptic density 95 (PSD-95) and growth-associated protein 43 (GAP-43) were studied in the frontal cortex of an autopsy series of 32 prospectively followed individuals (92-105 years) with a range of cognitive function. SYN protein levels were decreased in individuals with dementia and increased in those with clinical signs of cognitive impairment insufficient for a diagnosis of dementia. SYN but neither PSD-95 nor GAP-43 protein levels were significantly correlated with mini-mental status examination (MMSE) scores. Frontal cortex SYN protein levels may protect neuronal function in oldest-old individuals and reflect compensatory responses that may be involved with maintaining cognition. © 2007 Elsevier Inc. All rights reserved.

In a sample of 100 community-dwelling older adults (mean age of 76), higher hope related to greater life satisfaction and better perceived physical health, but hope did not relate to number of illnesses or functional disability. The high-relative to low-hope participants were more confident of reaching their goals, and felt that they were further along in their goal pursuits. The implications of these findings are discussed.

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