Introduction This study estimated the minimal clinically important difference (MCID) for Mini Mental State Examination, Clinical Dementia Rating Scale sum of boxes, and Functional Activities Questionnaire across the Alzheimer's disease (AD) spectrum. Methods Retrospective analysis of the National Alzheimer's Coordinating Center Uniform Data Set (9/2005-9/2016) and MCID for clinical outcomes were estimated using anchor-based (clinician's assessment of meaningful decline) and distribution-based (1/2 baseline standard deviation) approaches, stratified by severity of cognitive impairment. Results On average, a 1-3 point decrease in Mini Mental State Examination, 1-2 point increase in Clinical Dementia Scale sum of boxes, and 3-5 point increase in Functional Activities Questionnaire were indicative of a meaningful decline. The MCID values generally increased by disease severity; the effect size and standardized response mean for those with meaningful decline were consistently in the acceptable ranges for MCID. Discussion These findings can inform design and interpretation of future clinical trials.

Background: Costs associated with early stages of Alzheimer's disease (AD; mild cognitive impairment [MCI] and mild dementia [MILD]) are understudied. Objective: To compare costs associated with MCI and MILD due to AD in the United States. Methods: Data included baseline patient/study partner medical history, healthcare resource utilization, and outcome assessments as part of a prospective cohort study. Direct, indirect, and total societal costs were derived by applying standardized unit costs to resources for the 1-month pre-baseline period (USD2017). Costs/month for MCI and MILD cohorts were compared using analysis of variance models. To strengthen the confidence of diagnosis, amyloid-␤ (A␤) tests were included and analyses were replicated stratifying within each cohort by amyloid status [ + /−].

Background:We aimed to obtain a better understanding of how different aspects of patient functioning affect key cost and caregiver outcomes in Alzheimer's disease (AD).Methods: Baseline data from a prospective observational study of community-living AD patients (GERAS) were used. Functioning was assessed using the Alzheimer's Disease Cooperative Study -Activities of Daily Living Scale. Generalized linear models were conducted to analyze the relationship between scores for total activities of daily living (ADL), basic ADL (BADL), instrumental ADL (IADL), ADL subdomains (confirmed through factor analysis) and individual ADL questions, and total societal costs, patient healthcare and social care costs, total and supervision caregiver time, and caregiver burden.Results: Four distinct ADL subdomains were confirmed: basic activities, domestic/household activities, communication, and outside activities. Higher total societal costs were associated with impairments in all aspects of ADL, including all subdomains; patient costs were associated with total ADL and BADL, and basic activities subdomain scores. Both total and supervision caregiver hours were associated with total ADL and IADL scores, and domestic/household and outside activities subdomain scores (greater hours associated with greater functional impairments). There was no association between caregiver burden and BADL or basic activities subdomain scores. The relationship between total ADL, IADL, and the outside activities subdomain and outcomes differed between patients with mild and moderate-to-severe AD.Conclusions: Identification of ADL subdomains may lead to a better understanding of the association between patient function and costs and caregiver outcomes at different stages of AD, in particular the outside activities subdomain within mild AD.

Objective:To identify, in caregivers of patients with Alzheimer’s disease (AD) dementia, factors associated with subjective (personal, physical, emotional, and social) and objective (informal caregiver time and costs) caregiver burden.Design:Prospective longitudinal European observational study: post-hoc analysis.Setting:Clinic.Participants:Community-dwelling patients in France and Germany aged ≥ 55 years (n = 969) with probable AD and their informal caregivers.Measurements:Mini-Mental State Examination (MMSE), Alzheimer’s Disease Cooperative Study—Activities of Daily Living (ADCS-ADL), 12-item Neuropsychiatric Inventory (NPI-12), Zarit Burden Interview (ZBI), informal caregiver basic and instrumental ADL hours (Resource Utilization in Dementia instrument), and informal caregiver costs. Mixed-effect models of repeated measures (MMRM) were run, including baseline and time-dependent covariates (change from baseline [CFB] to 18 months in MMSE, ADCS-ADL, and NPI-12 scores) associated with CFB in ZBI score/informal caregiver time over 36 months (analyzed using linear regression models) and informal caregiver costs over 36 months (analyzed using generalized linear models).Results:Greater decline in patient function (ADCS-ADL) over 18 months was associated with increased subjective caregiver burden (ZBI), hours, and costs over 36 months. Increased behavioral problems (NPI-12) over 18 months also negatively impacted ZBI. Cognitive decline (MMSE) over 18 months did not affect change in caregiver burden.Conclusions:Long-term informal caregiver burden was driven by worsening functional abilities and behavioral symptoms but not cognitive decline, over 18 months in community-dwelling patients with AD dementia. Identifying the drivers of caregiver burden could highlight areas in which interventions may benefit both caregivers and patients.

Introduction This study evaluates rates of all-cause emergency department visits, all-cause hospitalizations, potentially avoidable hospitalizations, and falls in 3 years preceding Alzheimer's disease (AD) diagnosis. Methods Patients with AD and controls with no cognitive impairment were identified from the Medicare claims data. Patients were required to be aged ≥ 65 years and have continuous Medicare enrollment for ≥4 years before the index date (AD cohort: first AD diagnosis in 2012–2014; controls: randomly selected medical claim). Outcomes for each preindex year were compared among propensity score-matched cohorts. Results Each year, before index, patients with AD were more likely to have all-cause emergency department visits, all-cause hospitalizations, potentially avoidable hospitalizations, and falls ( P < .05 for all comparisons) than matched controls (N = 19,679 pairs). Increasing absolute and relative risks over time were observed for all outcomes. Discussion The study findings highlight the growing burden of illness before AD diagnosis and emphasize the need for timely recognition and management of patients with AD.

Although the AWV is correlated with an increase in some measures of cognitive care, such as laboratory testing for reversible causes of cognitive impairment, it does not appear to substantially increase recognition of undetected ADRD.

Background:Alzheimer’s disease (AD) is one of the costliest diseases in the United States.Objective:To describe aspects of real-world patient and caregiver burden in patients with clinician-diagnosed early AD, including mild cognitive impairment (MCI) and mild dementia (MILD) due to AD.Methods:Cross-sectional assessment of GERAS-US, a 36-month cohort study of patients seeking care for early AD. Eligible patients were categorized based on study-defined categories of MCI and MILD and by amyloid positivity [+] or negativity [–] within each severity cohort. Demographic characteristics, health-related outcomes, medical history, and caregiver burden by amyloid status are described.Results:Of 1,198 patients with clinician-diagnosed early AD, 52% were amyloid[+]. For patients in both cohorts, amyloid[–] was more likely to occur in those with: delayed time to an AD-related diagnosis, higher rates of depression, poorer Bath Assessment of Subjective Quality of Life in Dementia scores, and Hispanic/Latino ethnicity (all p < 0.05). MILD[–] patients (versus MILD[+]) were more medically complex with greater rates of depression (55.7% versus 40.4%), sleep disorders (34.3% versus 26.5%), and obstructive pulmonary disease (11.8% versus 6.6%); and higher caregiver burden (Zarit Burden Interview) (all p < 0.05). MILD[+] patients had lower function according to the Functional Activities Questionnaire (p < 0.001), yet self-assessment of cognitive complaints across multiple measures did not differ by amyloid status in either severity cohort.Conclusions:Considerable patient and caregiver burden was observed in patients seeking care for memory concerns. Different patterns emerged when both disease severity and amyloid status were evaluated underscoring the need for further diagnostic assessment and care for patients.Study Registry:H8A-US-B004; ClinicalTrials.gov: NCT02951598.

Duloxetine appears to be a cost-effective post-first-line treatment for CLBP compared with all but generic NSAIDs. In subpopulations at risk of NSAID-related AEs, it is particularly cost-effective.