Psychometric Evaluation of the Perceived Research Burden Assessment (PeRBA) in Longitudinal Studies of Alzheimer Disease Using Rasch Analysis.

INTRODUCTION: The Perceived Research Burden Assessment (PeRBA) was developed to measure participant perceptions of burden in research studies. This study aimed to examine the psychometric properties of this assessment using Rasch analysis in participants in the longitudinal studies of the Alzheimer disease (AD) and their family members. METHODS: PeRBA was administered to 443 participants in studies of AD and 212 family members across 4 Alzheimer Disease Research Centers. We used Rasch analysis to examine PeRBA's psychometric properties, and data-model fit both at item and scale levels. RESULTS: PeRBA demonstrated good reliability and item and person fit for participants and family members. A few items did not fit the model for participants or family members. Areas of content redundancy were found in items assessing similar amounts of perceived research burden. Areas of content gaps were also found, with no items assessing certain levels of perceived research burden. CONCLUSION: Analysis results support the good overall psychometric properties of PeRBA among research participants in studies of AD and their family members. Recommendations have been provided to improve the assessment, including rewording items and adding items that could account for a broader range of perceived research burden.

Falls and Alzheimer Disease.

Falls are the leading cause of injury, disability, and injury-related mortality in the older adult population. Older adults with Alzheimer disease (AD) are over twice as likely to experience a fall compared to cognitively normal older adults. Intrinsic and extrinsic fall risk factors may influence falls during symptomatic AD; intrinsic factors include changes in cognition and impaired functional mobility, and extrinsic factors include polypharmacy and environmental fall hazards. Despite many known fall risk factors, the high prevalence of falls, and the presence of effective fall prevention interventions for older adults without cognitive impairment, effective fall prevention interventions for older adults with AD to date are limited and inconclusive. Falls may precede AD-related cognitive impairment during the preclinical phase of AD, though a narrow understanding of fall risk factors and fall prevention interventions for older adults with preclinical AD limits clinical treatment of falls among cognitively normal older adults with preclinical AD. This mini review explores fall risk factors in symptomatic AD, evidence for effective fall prevention interventions in symptomatic AD, and preclinical AD as an avenue for future falls research, including recommendations for future research directions to improve our understanding of falls and fall risk during preclinical AD. Early detection and tailored interventions to address these functional changes are needed to reduce the risk of falls for those at risk for developing AD. Concerted efforts should be dedicated to understanding falls to inform precision fall prevention strategies for this population.

The Association Between Postural Sway and Preclinical Alzheimer Disease Among Community-Dwelling Older Adults.

BACKGROUND: It is unknown whether older adults with preclinical Alzheimer disease (AD) experience changes in postural sway compared with those without preclinical AD. The purpose of this study was to understand the effect of dual tasking on standing balance, or postural sway, for people with and without preclinical AD. METHODS: A cross-sectional analysis of baseline data from a longitudinal cohort study. Participants were cognitively normal older adults with and without preclinical AD. Postural sway (path length) was tested using a force plate under standard and dual task balance conditions. Dual task cost (DTC) was calculated to examine performance change in balance conditions. Logistic regression models were used to predict preclinical AD status as a function of DTC. RESULTS: 203 participants (65 preclinical AD+) were included. DTC for path length was significantly greater for participants with preclinical AD (DTC path length mean difference 19.8, 95% CI 2.6-37.0, t(201) = 2.29, p = .024). Greater DTC was significantly associated with increased odds of having preclinical AD (adjusted odds ratio for a 20-unit increase in DTC 1.16, 95% CI 1.02-1.32). CONCLUSIONS: Older adults with preclinical AD are more likely to demonstrate significantly greater DTC in postural sway than those without preclinical AD. Dual tasking should be integrated into balance and fall risk assessments and may inform early detection of preclinical AD.

Precipitating Mechanisms of Falls in Preclinical Alzheimer's Disease.

Background: Individuals with Alzheimer's disease (AD) are more than twice as likely to incur a serious fall as the general population of older adults. Although AD is commonly associated with cognitive changes, impairments in other clinical measures such as strength or functional mobility (i.e., gait and balance) may precede symptomatic cognitive impairment in preclinical AD and lead to increased fall risk. Objective: To examine mechanisms (i.e., functional mobility, cognition, AD biomarkers) associated with increased falls in cognitively normal older adults. Methods: This 1-year study was part of an ongoing longitudinal cohort study. We examined the relationships among falls, clinical measures of functional mobility and cognition, and neuroimaging AD biomarkers in cognitively normal older adults. We also investigated which domain(s) best predicted fall propensity and severity through multiple regression models. Results: A total of 182 older adults were included (mean age 75 years, 53% female). A total of 227 falls were reported over the year; falls per person ranged from 0-16 with a median of 1. Measures of functional mobility were the best predictors of fall propensity and severity. Cognition and AD biomarkers were associated with each other but not with the fall outcome measures. Conclusion: These results suggest that, although subtle changes in cognition may be more closely associated with AD neuropathology, functional mobility indicators better predict falls in cognitively normal older adults. This study adds to our understanding of the mechanisms underlying falls in older adults and could lead to the development of targeted fall prevention strategies.

Retention of Study Partners in Longitudinal Studies of Alzheimer Disease.

BACKGROUND: Study partners are required for all participants at Alzheimer's Disease Research Centers (ADRCs). Study partners' attitudes and beliefs may contribute to missed visits and negatively impact retention of participants in longitudinal AD studies. OBJECTIVE: Study partners (N = 212) of participants (Clinical Dementia Rating® [CDR]≤2) at four ADRCs were randomly surveyed to examine their facilitators and barriers to continued participation in AD studies. METHODS: Reasons for participation were analyzed with factor analysis and regression analysis. Effects of complaints and goal fulfillment on attendance were estimated with fractional logistic models. Open-ended responses were characterized with a Latent Dirichlet Allocation topic model. RESULTS: Study partners participated for personal benefit and altruism. They emphasized personal benefits more when their participants had a CDR > 0 than when they had a CDR = 0. This difference declined with participant age. The majority of study partners rated their ADRC participation as positive and meeting their goals. Although half reported at least one complaint, very few regretted participating. Those who reported that ADRC participation fulfilled their goals or had fewer complaints were more likely to have perfect attendance. Study partners requested more feedback about test results and better management of study visits. CONCLUSION: Study partners are motivated by both personal and altruistic goals. The salience of each goal depends on their trust in researchers and the participant's cognitive status and age. Retention may improve with perceived goal fulfillment and fewer complaints. Potential areas for improving retention are providing more information about the participant's test results and better management of study visits.

Assessment of Instrumental Activities of Daily Living in Preclinical Alzheimer Disease.

Questionnaires are used to assess instrumental activities of daily living (IADL) among individuals with preclinical Alzheimer disease (AD). They have indicated no functional impairment among this population. We aim to determine among cognitively normal (CN) older adults with and without preclinical AD whether: (a) performance-based IADL assessment measures a wider range of function than an IADL questionnaire and (b) biomarkers of AD are associated with IADL performance. In this cross-sectional analysis of 161 older adults, participants in studies of AD completed an IADL questionnaire, performance-based IADL assessment, cognitive assessments, and had biomarkers of AD (amyloid, hippocampal volume, brain network strength) assessed within 2 to 3 years. Performance-based IADL scores were more widely distributed compared with the IADL questionnaire. Smaller hippocampal volumes and reduced brain network connections were associated with worse IADL performance. A performance-based IADL assessment demonstrates functional impairment associated with neurodegeneration among CN older adults.

Falls: a marker of preclinical Alzheimer disease: a cohort study protocol.

INTRODUCTION: Progression to symptomatic Alzheimer disease (AD) occurs slowly over a series of preclinical stages. Declining functional mobility may be an early indicator of loss of brain network integration and may lead to an increased risk of experiencing falls. It is unknown whether measures of functional mobility and falls are preclinical markers of AD. The purpose of this study is to examine (1) the relationship between falls and functional mobility with AD biomarkers to determine when falls occur within the temporal progression to symptomatic Alzheimer disease, and (2) the attentional compared with perceptual/motor systems that underlie falls and functional mobility changes seen with AD. METHODS AND ANALYSIS: This longitudinal cohort study will be conducted at the Knight Alzheimer Disease Research Center. Approximately 350 cognitively normal participants (with and without preclinical AD) will complete an in-home visit every year for 4 years. During each yearly assessment, functional mobility will be assessed using the Performance Oriented Mobility Assessment, Timed Up and Go, and Timed Up and Go dual task. Data regarding falls (including number and severity) will be collected monthly by self-report and confirmed through interviews. This study will leverage ongoing neuropsychological assessments and neuroimaging (including molecular imaging using positron emission tomography and MRI) performed by the Knight Alzheimer Disease Research Center. Relationships between falls and biomarkers of amyloid, tau and neurodegeneration will be evaluated. ETHICS AND DISSEMINATION: This study was approved by the Washington University in St. Louis Institutional Review Board (reference number 201807135). Written informed consent will be obtained in the home prior to the collection of any study data. Results will be published in peer-reviewed publications and presented at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04949529; Pre-results.

A Mixed Methods Study Exploring Older Womens' Attitudes Toward Osteoporosis Medications: Adapting a Health Communication Framework.

Background: Bisphosphonates (BPs) can reduce fracture risk for adults with osteoporosis (OP), but they have rare risks, complicating decision making. Guided by an established health decision and communication framework, we explored older women's feelings and positions toward taking BPs. Materials and Methods: Using a mixed-methods design, we interviewed women >65 years of age who had never taken BPs. After learning about BPs, participants responded to items about their feelings toward medication benefits/risks. They then identified their overall position toward taking BPs (corresponding to Unquestioning Acceptors, Cautious Acceptors, Hesitants, Probable Refusers, and Definite Refusers). We analyzed data using qualitative content analysis and summarized quantitative data with descriptive statistics. Results: Thirty women participated. Acceptors (N = 17, 56.6%) worried about OP-related fractures. Hesitant participants (N = 12, 40%) worried about BP risks, yet expressed openness toward medications if given opportunities to gather information and talk to clinicians. One Refuser expressed distrust in clinicians and pharmaceuticals. Conclusions: Understanding women's positions toward BPs might improve decision-making processes for OP treatment. Clinicians could tailor communication based on patients' identified BP position. Acceptors might be comfortable with succinct conversations describing medications. Hesitant patients might need more information from resources such as decision aids. Building trust with patients questioning BPs can support future conversations.

Falls Associate with Neurodegenerative Changes in ATN Framework of Alzheimer's Disease.

BACKGROUND: Behavioral markers for Alzheimer's disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework. OBJECTIVE: To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD. METHODS: This cross-sectional study recorded falls among CN participants (n = 83) over a 1-year period. Tailored calendar journals recorded falls. Biomarkers including amyloid positron emission tomography (PET) and structural and functional magnetic resonance imaging were acquired within 2 years of fall evaluations. CN participants were dichotomized by amyloid PET (using standard cutoffs). Differences in amyloid accumulation, global resting state functional connectivity (rs-fc) intra-network signature, and hippocampal volume were compared between individuals who did and did not fall using Wilcoxon rank sum tests. Among preclinical AD participants (amyloid-positive), the partial correlation between amyloid accumulation and global rs-fc intra-network signature was compared for those who did and did not fall. RESULTS: Participants who fell had smaller hippocampal volumes (p = 0.04). Among preclinical AD participants, those who fell had a negative correlation between amyloid uptake and global rs-fc intra-network signature (R = -0.75, p = 0.012). A trend level positive correlation was observed between amyloid uptake and global rs-fc intra-network signature (R = 0.70, p = 0.081) for preclinical AD participants who did not fall. CONCLUSION: Falls in CN older adults correlate with neurodegeneration biomarkers. Participants without falls had lower amyloid deposition and preserved global rs-fc intra-network signature. Falls most strongly correlated with presence of amyloid and loss of brain connectivity and occurred in later stages of preclinical AD.