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INTRODUCTION: For many patients and caregivers, a major goal of disease-modifying treatments (DMT) for Alzheimer disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs. METHODS: Participants at the Knight Alzheimer Disease Research Center were selected who were potentially eligible for recent DMT trials: age ≥ 60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating® (CDR®) score 0.5 or 1), biomarker confirmation of amyloid pathology, and at least one follow-up CDR assessment within 5 years. For IADLs, a subset of the Functional Assessment Questionnaire (FAQ) was examined that rated the degree of independence in the following: paying bills, driving, remembering medications and appointments, and preparing meals. For BADLs, the Personal Care domain of the CDR was used. Mixed-effects logistic and ordinal regression models were used to examine the relationship between CDR Sum Boxes (CDR-SB) and the individual functional outcomes and their components. The change in CDR-SB over time was estimated with linear mixed effects models. RESULTS: 282 participants were followed for an average of 2.9 years (SD 1.3 years). For 50% of individuals, loss of independence in IADLs occurred at CDR-SB>4.5 and in BADLs at CDR-SB>11.5. For individuals with a baseline CDR-SB=2, treatment with lecanemab would extend independence in IADLs for 10 months (95% CI 4-18 months) and treatment with donanemab in the low/medium tau group would extend independence in IADLs by 13 months (95% CI 6-24 months). DISCUSSION: Independence in ADLs can be related to CDR-SB and used to demonstrate the effect of AD treatments in extending the time of independent function, a meaningful outcome for patients and their families.
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INTRODUCTION: Research addressing Alzheimer disease and related dementias must examine nonbiological factors influencing the risk for and expression of Alzheimer disease and related dementias. These factors address the interplay of cognition with lived experiences and social and structural determinants of health (SSDOH). However, coordinated measures of SSDOH are limited. METHODS: The Knight Alzheimer Disease Research Center (ADRC) at Washington University in St. Louis developed and piloted a comprehensive battery to measure SSDOH. One hundred and twelve participants, very mildly cognitively impaired or unimpaired, enrolled in memory studies completed the electronic SSDOH battery. The Clinical Dementia Rating (CDR) determined the presence or absence of cognitive impairment. RESULTS: Four domains demonstrated above acceptable intraclass correlation scores for test-retest reliability (≥0.70), including adverse childhood events, discrimination, social status, and early education. Twenty very mildly impaired participants completed the electronic pilot study. CONCLUSION: Our findings indicate that participants with early-stage symptomatic Alzheimer disease are able to participate in electronic SSDOH data collection. In collaboration with the University of Pennsylvania ADRC, we replaced/modified certain assessments to increase intraclass correlation. The resulting battery, Social and Structural Life-courses Influencing Aging and Dementia (SS-DIAD), can serve as a SSDOH collection tool and is currently utilized in cognitively impaired and unimpaired research participants at both ADRCs.
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Enfermedad de Alzheimer , Trastornos del Conocimiento , Enfermedad de Alzheimer/psicología , Niño , Trastornos del Conocimiento/psicología , Humanos , Proyectos Piloto , Reproducibilidad de los Resultados , Determinantes Sociales de la SaludRESUMEN
Structural and social determinants of health (SSDoH) are environmental conditions in which individuals are born, live, learn, work, play, worship, and age that affect health, functioning, and quality-of-life outcomes across the life course. Growing evidence suggests that SSDoH can help to explain heterogeneity in outcomes in Alzheimer's disease and Alzheimer's disease and related dementias (AD/ADRD) research and clinical practice. The National Institute on Aging has prioritized collecting SSDoH data to elucidate disease mechanisms and aid discovery of disease-modifying treatments. However, a major nexus of AD/ADRD research, the national network of Alzheimer's Disease Research Centers (ADRCs), collects few SSDoH data. We describe a framework for feasibly gathering and modeling SSDoH data across ADRCs. We lay out key constructs, their measures, and empirical evidence for their importance in elucidating disease and prevention mechanisms. Toward a goal of translation, the framework proposes a modular structure with a core set of measures and options for adjunctive modules. We describe considerations for measuring SSDoH in existing geographically and culturally diverse research cohorts. We also outline a rationale for universal implementation of a set of SSDoH measures and juxtapose the approach with alternatives aimed at collecting SSDoH data.