Quality of Life and Utility Measurement in a Large Clinical Trial Sample of Patients with Mild to Moderate Alzheimer's Disease: Determinants and Level of Changes Observed.

OBJECTIVE: To evaluate the performance (in terms of responsiveness to change, associations with other criterion standards, and indicators of Alzheimer's disease [AD] severity) of a quality-of-life measure (Quality of Life in Alzheimer's Disease [QOL-AD]) and a health utility measure (Health Utilities Index Mark 3 [HUI-3]) from two recently completed clinical trials of a new drug for AD. METHODS: Change from baseline scores was calculated, and treatment effects were analyzed using mixed models for repeated measures. Three separate models were then estimated to examine the association between the quality-of-life/utility end points and the clinical and other health outcome end points measured during the trials, including cognition, function, behavior, and dependence. RESULTS: The performance of the two measures differed. Subject-assessed QOL-AD was found to be weakly associated with clinical measures of cognition, and with caregiver reports of function, behavior, and dependence, and showed little movement over time and did not appear to differ by baseline AD severity. Proxy-assessed QOL-AD scores were consistently lower than subject-assessed scores, and the level of decline in QOL-AD was greater using proxy-assessed QOL-AD. Proxy-assessed HUI-3 scores were more strongly associated with clinical measures of cognition, function, behavior, and dependence than the subject- and proxy-assessed QOL-AD scores. Larger proportionate changes over 78 weeks were observed with HUI-3 scores and greater separation in HUI-3 scores by baseline severity. CONCLUSIONS: Subject-assessed QOL-AD is less likely than proxy-assessed QOL-AD to respond to changes in clinical measures used to track progression in clinical trials of subjects with mild to moderate AD. Proxy-assessed HUI-3 assessments were more in line with other outcome assessments and could therefore be better outcome measures to evaluate clinical progression in mild to moderate AD.

Taking stock: A multistakeholder perspective on improving the delivery of care and the development of treatments for Alzheimer's disease.

Health-care stakeholders increasingly recognize that the scientific and economic challenges associated with Alzheimer's disease (AD) are simply too great for individual stakeholder groups to address solely from within their own silos. In the necessary spirit of collaboration, we present in this perspective a set of multicountry multistakeholder recommendations to improve the organization of existing AD and dementia care and the development of new treatments. In brief, the five recommendations are (1) health-care systems must make choices regarding the patient populations to be diagnosed and treated, (2) health-care systems should use an evidence-based standard of care, (3) increased collaboration between public and private institutions is needed to enhance research, (4) reimbursement end points need to be agreed on and validated, and (5) innovative business models should be used to spur the introduction of new medicines.

Reliability, validity, and interpretation of the dependence scale in mild to moderately severe Alzheimer's disease.

INTRODUCTION: The Dependence Scale (DS) was designed to measure dependence on others among patients with Alzheimer's disease (AD). The objectives of this research were primarily to strengthen the psychometric evidence for the use of the DS in AD studies. METHODS: Patients with mild to moderately severe AD were examined in 3 study databases. Within each data set, internal consistency, validity, and responsiveness were examined, and structural equation models were fit. RESULTS: The DS has strong psychometric properties. The DS scores differed significantly across known groups and demonstrated moderate to strong correlations with measures hypothesized to be related to dependence (|r| ≥ .31). Structural equation modeling supported the validity of the DS concept. An anchor-based DS responder definition to interpret a treatment benefit over time was identified. DISCUSSION: The DS is a reliable, valid, and interpretable measure of dependence associated with AD and is shown to be related to--but provides information distinct from--cognition, functioning, and behavior.

Staging dementia from symptom profiles on a care partner website.

BACKGROUND: The World Wide Web allows access to patient/care partner perspectives on the lived experience of dementia. We were interested in how symptoms that care partners target for tracking relate to dementia stage, and whether dementia could be staged using only these online profiles of targeted symptoms. OBJECTIVES: To use clinical data where the dementia stage is known to develop a model that classifies an individual's stage of dementia based on their symptom profile and to apply this model to classify dementia stages for subjects from a Web-based dataset. METHODS: An Artificial Neural Network (ANN) was used to identify the relationships between the dementia stages and individualized profiles of people with dementia obtained from the 60-item SymptomGuide (SG). The clinic-based training dataset (n=320), with known dementia stages, was used to create an ANN model for classifying stages in Web-based users (n=1930). RESULTS: The ANN model was trained in 66% of the 320 Memory Clinic patients, with the remaining 34% used to test its accuracy in classification. Training and testing staging distributions were not significantly different. In the 1930 Web-based profiles, 309 people (16%) were classified as having mild cognitive impairment, 36% as mild dementia, 29% as moderate, and 19% as severe. In both the clinical and Web-based symptom profiles, most symptoms became more common as the stage of dementia worsened (eg, mean 5.6 SD 5.9 symptoms in the MCI group versus 11.9 SD 11.3 in the severe). Overall, Web profiles recorded more symptoms (mean 7.1 SD 8.0) than did clinic ones (mean 5.5 SD 1.8). Even so, symptom profiles were relatively similar between the Web-based and clinical datasets. CONCLUSION: Symptoms targeted for online tracking by care partners of people with dementia can be used to stage dementia. Even so, caution is needed to assure the validity of data collected online as the current staging algorithm should be seen as an initial step.

Validation of an informant-reported web-based data collection to assess dementia symptoms.

BACKGROUND: The Web offers unprecedented access to the experience of people with dementia and their care partners, but data gathered online need to be validated to be useful. OBJECTIVE: To test the construct validity of an informant Web-based data collection to assess dementia symptoms in relation to the 15-point Dependence Scale (DS). METHODS: In an online survey posted on the DementiaGuide website, care partners of people with dementia built individualized profiles from the 60-item SymptomGuide and completed a questionnaire, which included the DS and a staging tool. RESULTS: In the 250 profilees (155, 62% women, mean age 77 years), increasing dependence was associated with a greater chance of institutionalization. For example, no one at the lowest levels of dependence (DS score < 5, n = 33) was in long-term care, compared with half (13/25) of the profilees at the highest levels of dependence (DS score > 12) being in institutions (χ(2)(4) = 27.9, P < .001). The Web-based DS was correlated with the number of symptoms: higher DS scores were associated with a higher stage of dementia (F > 50, P < .001). CONCLUSION: In an online survey, the Web-based DS showed good construct validity, potentially demonstrating how the Web can be used to learn more about dementia progression and how it relates to symptoms experienced by patients across the course of dementing illnesses. Even so, caution is needed to assure the validity of data collected online.

A qualitative assessment of the concept of dependence in Alzheimer's disease.

BACKGROUND: The Dependence Scale (DS) was designed to assess levels of patient need for care due to deficits typical of Alzheimer's disease (AD). This study examined content validity of the DS based on input from patients, caregivers, and clinicians. METHODS: Qualitative interviews with experts, patients, and caregivers were used to collect information on the concept of dependence and to assess content validity. RESULTS: Nine clinicians rated item relevance ''high'' with consensus on the primacy of functional abilities and dependence in the measurement of AD progression. Twenty-two US, 11 UK, and 14 informal caregivers from Spain participated in focus groups; 18 patients participated in 3 separate focus groups. Discussion supported DS hierarchy of dependence, capture of mild-to-severe dependence, suitability of response options, and short recall time frame. CONCLUSIONS: Clinicians, caregivers, and patients support content validity of the DS in mild-to-moderate AD. The DS may be valuable to capture dependence within future clinical dementia trials.