Effect of gamification with a support partner to increase physical activity in older adults at risk for Alzheimer's disease: The STEP 4Life randomized clinical trial.

INTRODUCTION: Physical activity is associated with reduced risk of cognitive and functional decline but scalable, sustainable interventions for populations at risk for Alzheimer's disease (AD) and AD and related dementias (ADRD) are lacking. METHODS: A 12-week randomized-controlled trial was conducted with a 3-week follow-up using a national AD prevention registry (GeneMatch). The control group (n = 50) set step goals and received daily feedback. The intervention group (n = 44) also received a behaviorally designed game based on achieving step goals and reinforced by a support partner. RESULTS: Intervention participants (94 participants, mean age 70, 78% female) had greater change in mean daily step count than control of 1699 steps/day (95% confidence interval [CI], 1149-2249), P < 0.0001, which was sustained in the follow-up period at 1219 steps/day (95% CI, 455-1983), P = 0.0018. Carriers of the apolipoprotein E ε4 gene (high risk) did not perform differently than non-carriers; however, high self-reported risk perception was associated with higher activity. DISCUSSION: A gamified intervention was effective in promoting and sustaining higher physical activity in older adults at genetic risk for AD/ADRD. HIGHLIGHTS: A simple game played with a support partner increased walking in older adults at risk for Alzheimer's disease (AD). The game also increased minutes of moderate-to-vigorous physical activity per day. Perception of lifelong AD risk was associated with increased activity but genetic risk (apolipoprotein E ε4+) was not. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05069155.

Double-Edged Sword: A Positive Brain Scan Result Heightens Confidence in an Alzheimer's Diagnosis but also Leads to Higher Stigma among Older Adults in a Vignette-Based Experiment.

OBJECTIVES: Early diagnosis of Alzheimer's disease (AD) using brain scans and other biomarker tests will be essential to increasing the benefits of emerging disease-modifying therapies, but AD biomarkers may have unintended negative consequences on stigma. We examined how a brain scan result affects AD diagnosis confidence and AD stigma. METHODS: The study used a vignette-based experiment with a 2×2×3 factorial design of main effects: a brain scan result as positive or negative, treatment availability and symptom stage. We sampled 1,283 adults ages 65 and older between 11 June and 3 July 2019. Participants (1) rated their confidence in an AD diagnosis in each of four medical evaluations that varied in number and type of diagnostic tools and (2) read a vignette about a fictional patient with varied characteristics before completing the Modified Family Stigma in Alzheimer's Disease Scale (FS-ADS). We examined mean diagnosis confidence by medical evaluation type. We conducted between-group comparisons of diagnosis confidence and FS-ADS scores in the positive versus negative brain scan result conditions and, in the positive condition, by symptom stage and treatment availability. RESULTS: A positive versus negative test result corresponds with higher confidence in an AD diagnosis independent of medical evaluation type (all p<0.001). A positive result correlates with stronger reactions on 6 of 7 FS-ADS domains (all p<0.001). DISCUSSION: A positive biomarker result heightens AD diagnosis confidence but also correlates with more AD stigma. Our findings inform strategies to promote early diagnosis and clinical discussions with individuals undergoing AD biomarker testing.

Determinants of Plasma Alzheimer's Disease Biomarker Use by Primary Care Providers and Dementia Specialists.

BACKGROUND: The efficiencies of plasma Alzheimer's disease (AD) biomarkers could facilitate early AD diagnosis. Unfortunately, limited knowledge exists about whether and how they would be used by clinicians. OBJECTIVE: To identify and compare determinants of plasma AD biomarker use reported by primary care providers and dementia specialists. DESIGN: Semi-structured interviews with clinicians organized using Rogers' Diffusion of Innovations theory and analyzed using an iterative coding approach. PARTICIPANTS: The subjects were internal and family medicine, neurology, and geriatrics providers with varying degrees of expertise in dementia diagnosis and care. MAIN MEASURES: Factors influencing a clinician's decision to use or not use plasma AD biomarkers in clinical practice. KEY RESULTS: We interviewed 30 clinicians (16 family or internal medicine providers, 8 geriatricians, and 6 neurologists). Fifteen were dementia specialists. Hesitance to use plasma AD biomarkers was due to perceived lack of effective treatments for AD, limited access to supports, and stigma. Plasma AD biomarkers would be more readily adopted by clinicians with dementia expertise. CONCLUSIONS: Several factors will influence clinical use of plasma AD biomarkers. Some of them may inform the design of interventions to promote the effective and appropriate clinical translation of these tests.

How reactions to a brain scan result differ for adults based on self-identified Black and White race.

INTRODUCTION: How do reactions to a brain scan result differ between Black and White adults? The answer may inform efforts to reduce disparities in Alzheimer's disease (AD) diagnosis and treatment. METHODS: Self-identified Black (n = 1055) and White (n = 1451) adults were randomized to a vignette of a fictional patient at a memory center who was told a brain scan result. Measures of stigma and diagnosis confidence were compared between-groups. RESULTS: Black participants reported more stigma than White participants on four of seven domains in reaction to the patient at a memory center visit. Black participants' confidence in an AD diagnosis informed by a brain scan and other assessments was 72.2 points (95% confidence interval [CI] 70.4 to 73.5), which was lower than the respective rating for White participants [78.1 points (95%CI 77.0 to 79.3)]. DISCUSSION: Equitable access to early AD diagnosis will require public outreach and education that address AD stigma associated with a memory center visit.

Caregiver Accounts of Lucid Episodes in Persons With Advanced Dementia.

BACKGROUND AND OBJECTIVES: Paradoxical lucidity is defined as an instance of unexpected lucid behavior in a person who is assumed to be noncommunicative due to a progressive and pathophysiologic dementing process. To inform studies of the prevalence, characteristics, and impact of these behaviors, this interview study examined caregivers' experiences of witnessing paradoxical lucidity. RESEARCH DESIGN AND METHODS: Participants were family caregivers of persons living with advanced dementia caused by a neurodegenerative disease producing significant impairments in communication. Semistructured interviews elicited the caregivers' experiences of plausible lucid episodes. Data analysis used a thematic analysis approach. RESULTS: Most caregivers reported at least 1 episode of lucidity. Episodes were typically brief. Most involved utterances, but nonverbal behaviors were also common. The mental capacities associated with these behaviors included recognition, awareness of surroundings, recognizing others' emotions, and goal-directed behavior. Most caregivers' reactions were positive. Episodes did not lead to changes in major medical decisions but instead to efforts to either modify or reinforce daily caregiving efforts. DISCUSSION AND IMPLICATIONS: Episodes of lucidity were common, a finding seen in other studies. If prevalence studies confirm this, the qualifier "paradoxical" should be eliminated. The caregivers' familiarity with the person living with dementia allowed them to attribute meaning to subtle behaviors that might not otherwise be detected or considered lucid. Clinicians who care for persons with advanced-stage dementia should routinely ask caregivers about episodes of lucid communication and their emotional reactions.

Cognitive Complaint Types Can Correlate With Cognitive Testing, Perceived Stress, and Symptom Distress in Older Adults With Normal Cognition and Dementia.

OBJECTIVE: We examined how cognitive complaint types (CCTs) correlate with cognitive testing, perceived stress, and symptom distress in older adults with normal cognition and dementia. METHODS: Older adults (n = 259) with normal cognition, mild cognitive impairment, or mild-stage Alzheimer disease completed cognitive testing and self-report measures (Cognitive Difficulties Scale, Global Distress Index, Perceived Stress Scale). Cross-sectional analyses examined: (1) CCT composition by classification method,( 2) CCTs by diagnostic group, (3) correlations of CCTs with cognitive testing scores, and (4) correlations of CCTs with perceived stress and symptom distress. RESULTS: CCTs derived from 2 classification approaches loaded onto 4 factors: memory, attention-concentration (AC), temporal orientation, and praxis. Memory contained complaints about both memory and executive functioning. AC contained both classifications of AC complaints. Complaints about AC (AC1 and AC2) differed by diagnostic group (all P < 0.05). One of 2 classifications of AC (AC1) complaints discerned between impaired and unimpaired long-delay memory scores (both P < 0.05). In multivariable analyses, that same classification of AC (AC1) complaints correlated with higher perceived stress (both P < 0.001) but not symptom distress (both P > 0.05). CONCLUSION: CCTs showed a factor structure that was mostly robust between classification methods; however, some content-divergent CCTs shared factors, suggesting construct overlap. Relatively slight variations in content altered how CCTs correlated with diagnostic groups, perceived stress, and symptom distress. Most CCTs did not discern between impaired and unimpaired cognitive test scores. Research is needed to better understand CCTs as clinical markers and targets of clinical interventions.

"A Raw Blessing" - Caregivers' Experiences Providing Care to Persons Living with Dementia in the COVID-19 Pandemic.

The COVID-19 pandemic has been devastating for people living with dementia (PLWD) and their caregivers. While prior research has documented these effects, it has not delved into their specific causes or how they are modified by contextual variation in caregiving circumstances.

Awareness of diagnosis predicts changes in quality of life in individuals with mild cognitive impairment and mild stage dementia.

BACKGROUND AND OBJECTIVE: This observational study examined how awareness of diagnosis predicted changes in cognition and quality of life (QOL) 1 year later in older adults with normal cognition and dementia diagnoses. RESEARCH DESIGN AND METHODS: Older adults (n = 259) with normal cognition, mild cognitive impairment (MCI), or mild stage Alzheimer's disease (AD) completed measures of diagnostic awareness, cognition, and multiple domains of QOL. We compared 1-year change in cognition and QOL by diagnostic group and diagnostic awareness. RESULTS: Patients who were unaware of their diagnosis at baseline showed average decreases in both satisfaction with daily life (QOL-AD; paired mean difference (PMD) = -0.9, p < 0.05) and physical functioning (SF-12 PCS; PMD = -2.5, p < 0.05). In contrast, patients aware of their diagnosis at baseline showed no statistically discernable changes in most QOL domains (all p > 0.05). Of patients aware of their diagnosis at baseline (n = 111), those who were still aware (n = 84) showed a decrease in mental functioning at follow up (n = 27; SF-12 MCS). Change in MoCA scores in patients unaware of their diagnosis was similar to that in patients aware of their diagnosis, -1.4 points (95% CI -2.6 to -0.6) and -1.7 points (95% CI -2.4 to -1.1) respectively. DISCUSSION AND IMPLICATIONS: Awareness of one's diagnosis of MCI or AD, not the severity of cognitive impairment, may predict changes in patients' mental functioning, expectations of their memory, satisfaction with daily life, and physical functioning. The findings may help clinicians anticipate the types of threats to wellbeing that a patient might encounter and identify key domains for monitoring.

How intention to join an Alzheimer's participant recruitment registry differs by race, ethnicity, sex, and family history: Results from a national survey of US adults.

INTRODUCTION: Alzheimer's-focused participant recruitment registries are tools for accelerating enrollment into studies, however, registry members are primarily White women. METHODS: We conducted a national online survey of 1501 adults ages 50-80, oversampling for Black and Hispanic/Latino respondents, assessing intention to join a generic "brain health" registry and to join a registry that required specific tasks. RESULTS: Intention to join a registry was low (M 3.48, SD 1.77), and lower than intention to join a registry requiring specific tasks. Intention was greatest for registries requiring completing surveys (M 4.70, SD 1.77). Differences in intention were primarily between White women and Black women; differences between other groups were limited to specific tasks required. DISCUSSION: The results indicate uncertainty about what a registry is, its purpose, and/or the concept of "brain health." Using the Reasoned Action Approach (RAA) to develop evidence-based outreach messages describing a registry and required tasks may increase diversity.

A systematic review of measures of gender and biological sex: Exploring candidates for Alzheimer's disease and related dementias (AD/ADRD) research.

Background: Gender and biological sex are social and structural determinants of health and umbrella concepts encompassing many distinct attributes. This systematic review summarizes measures of gender and biological sex published in the biomedical literature. The goal was to identify measures that may be useful to researchers studying Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). Methods: A search of PubMed, Embase, and PsycINFO (ProQuest platform) databases from 2000 to 2021 identified 1454 articles, which were then screened by five independent reviewers. Measures of gender and biological sex are summarized according to theoretical commitments and psychometric properties. Results: Twenty-nine measures were identified that assessed gender-related constructs, and 4 were identified that assessed biological factors. Self-report instruments characterized aspects of gender, such as gender stereotypes, norms, and ideologies. One measure was developed with a focus on older adults (65+ years). Discussion: We offer recommendations to guide measurement of gender in AD/ADRD research, including how the use of specific existing measures may help advance AD/ADRD research. The lack of gender measures for older adults limits AD/ADRD research. New measures may be needed to address lifespan and generational differences in gender factors. Highlights: A review of articles identifies 29 measures of gender in biomedical research.Gender is captured using multidimensional, self-reported concepts.One measure was developed with a focus on older adults (65+).

Gender of Study Partners and Research Participants Associated With Differences in Study Partner Ratings of Cognition and Activity Level.

OBJECTIVES: Studies of Alzheimer's disease typically include "study partners" (SPs) who report on participants' cognition and function. Prior studies show SP reports differ depending on the relationship between the SP and participant, that is, spouse or adult child. Adult children SPs are typically female. Could differing reports be due to gender? Knowing this may help explain variability in measurement. METHODS: The Aging, Demographics, and Memory Study enrolled a subset of participants from the Health and Retirement Study. Each participant had an SP. Bivariate and multivariable regression models compared 718 SP-participant dyads. RESULTS: In analyses of 4 groups defined by SP and participant gender, dyads composed of 2 women were less likely to identify as White (75.8%, 95% confidence interval [CI], 70.4-80.5) than dyads composed of 2 men (93.3%, 95% CI, 81.2-97.8). In analyses adjusted for the severity of cognitive and functional impairment, women SPs rated women participants as more active than they rated men, mean 2.15 (95% CI, 2.07-2.22) versus mean 2.30 (95% CI, 2.24-2.37), respectively, on a 4-point scale. Similarly, men SPs rated women participants as more active than they rated men, mean 2.1 (95% CI, 2.0-2.2) and mean 2.4 (95% CI, 2.3-2.5), respectively. In an analysis of cognitively unimpaired participants, women SPs rated participants' memory worse than men SPs did (p < .05). DISCUSSION: SP and participant gender influence SPs' reports of another person's cognition and activity level. Our findings expand what is understood about how nondisease factors influence measures of disease severity.

Testing for Alzheimer Disease Biomarkers and Disclosing Results Across the Disease Continuum.

Three pathologic processes are characteristic of Alzheimer disease (AD): ß-amyloid, hyperphosphorylated tau, and neurodegeneration. Our understanding of AD is undergoing a transformation due to our ability to measure biomarkers of these processes across different stages of cognitive impairment. There is growing interest in using AD biomarker tests in care and research and, with this, a growing need for guidance on how to return these sensitive results to patients and participants. Here, we propose a 5-step approach informed by clinical and research experience designing and implementing AD biomarker disclosure processes, extant evidence describing how individuals react to AD biomarker information, ethics, law, and the literature on breaking bad news. The clinician should (1) determine the appropriateness of AD biomarker testing and return of results for the particular patient or research participant. If testing is appropriate, the next steps are to (2) provide pretest education and seek consent for testing from the individual and their support person, (3) administer testing, (4) return the results to the individual and their support person, and (5) follow-up to promote the recipient's well-being.

An Elicitation Study to Understand Black, Hispanic, and Male Older Adults' Willingness to Participate in Alzheimer's Disease-Focused Research Registries.

BACKGROUND: There is a lack of racial, ethnic, and sex diversity in recruitment research registries and Alzheimer's disease (AD) research studies and trials. Theory-based recruitment messages may provide an opportunity to increase study participant diversity in AD research studies and trials. OBJECTIVE: To identify behavioral, normative, and control beliefs that are associated with joining an AD-focused recruitment registry among historically underrepresented groups. METHOD: Using a Reasoned Action Approach, we conducted 60 semi-structured phone interviews in 2020 among White, Black, and Hispanic adults ages 49-79 years in Philadelphia, PA. Underlying beliefs were elicited for the target behavior of "signing up to be on a registry for brain health research studies in the next month." Percentages based on counts are reported for the overall sample and by race and ethnicity and sex. RESULTS: Participants were most concerned that if they were to sign up for a registry, they would be asked to participate in experimental studies. Advancing science to help others was a commonly reported positive belief about signing up. Participants' children and friends/neighbors were important from a normative perspective. Barriers to enrollment focused on logistical concerns and inconvenient sign-up processes, including using a computer. Results show generally few racial and ethnic or sex group differences. CONCLUSION: The elicited beliefs from underrepresented groups offer a basis for understanding the behavior of signing up for research registries. However, there were few differences between the groups. Implications for outreach and recruitment are discussed.

Predictors of who Serves as an Alzheimer's Disease Research Participant's Study Partner and the Impact of their Relationship on Study Partners' Reports on Participants.

Background: Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) research typically requires participants to enroll with a "study partner" (SP). Little is known about what predicts who steps into the SP role or whether the SP's relationship to the participant affects their reports of disease severity.Methods: Health and Retirement Study data (HRS), collected prior to the Aging, Demographics and Memory Study (ADAMS), was used to identify sociocultural factors that predict who serves as a SP in ADAMS. SP-reported outcomes were compared between three types of participant-SP relationships: spousal, adult child, and other.Results: Spouses (35%) and adult children (39%) were similarly likely to serve as SPs. Factors predicting who served differed. In multivariable analyses, adult children rated participants less impaired than spouses on measures of memory, judgment, and organizational abilities (p < .05). Conclusions: The participant-SP relationship has independent effects on the SP's reports of the severity of cognitive impairments.

You've Got a Friend in Me: How Cognitively Unimpaired Older Adults Select a Study Partner to Participate with Them in Alzheimer's Disease Research.

BACKGROUND: Participants in Alzheimer's disease (AD) prevention studies are generally required to enroll with a study partner; this requirement constitutes a barrier to enrollment for some otherwise interested individuals. Analysis of dyads enrolled in actual AD trials suggests that the study partner requirement shapes the population under study. OBJECTIVE: To understand if individuals can identify someone to serve as their study partner and whether they would be willing to ask that individual. METHODS: We conducted semi-structured interviews with cognitively unimpaired, English-speaking older adults who had previously expressed interest in AD research by signing up for a research registry. We also interviewed their likely study partners. Audio-recorded interviews were transcribed and coded in an iterative, team-based process guided by a content analysis approach. RESULTS: We interviewed 60 potential research participants and 17 likely study partners. Most potential participants identified one or two individuals they would be willing to ask to serve as their study partner. Interviewees saw value in the study partner role but also understood it to entail burdens that could make participation as a study partner difficult. The role was seen as relatively more burdensome for individuals still in the workforce or with family responsibilities. Calls from the researcher to discuss the importance of the role and the possibility of virtual visits were identified as potential strategies for increasing study partner availability. CONCLUSION: Efforts to increase recruitment, particularly representative recruitment, of participants for AD prevention studies should reduce barriers to participation by thoughtfully designing the study partner role.

Measuring Sex and Gender in Aging and Alzheimer's Research: Results of a National Survey.

OBJECTIVES: Differences between men and women are common in published research on aging and Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD). What do these differences mean? To answer this, rigorous measurement is needed. We investigated current methods for measuring sex/gender in aging and AD/ADRD cohort studies. METHODS: An online survey was sent to National Institute on Aging-funded Alzheimer's Disease Research Centers (n = 38) and investigator-initiated cohort studies (n = 38) to assess practices around enrollment of men and women and measurement of sex and gender. RESULTS: The response rate was 65.8% (n = 50). All enrolled men and all but two investigator-initiated studies enrolled women. Most cohorts (43/50) had no documented definitions for categories of "men" or "women." Over 85% of cohorts relied solely on self-report questions to capture sex/gender data (n = 43/50). Issues with administration were also identified (n = 7). DISCUSSION: Our findings identify gaps in current approaches used to measure sex and gender in aging and AD/ADRD research. We discuss opportunities to bridge these gaps and advance measurement of sex and gender in aging and AD/ADRD research. Changes are needed to ensure inclusion and representation of sociocultural diversity in research samples, and consistency in data collection in aging and AD/ADRD research.

What is paradoxical lucidity? The answer begins with its definition.

Paradoxical lucidity in dementia is a clinically significant but understudied phenomenon. A provisional definition was proposed by the 2018 National Institute on Aging expert workshop and published in Alzheimer's and Dementia. However, several conceptual features of this definition remain vague, creating barriers to robust clinical research. Here, we critically analyze the provisional definition and present a refined definition that can be applied in clinical research. The refined definition is based on an analytic process our research group recently undertook to operationalize paradoxical lucidity for our own study protocol. Our goal is to facilitate debate and potentially harmonize interpretations of paradoxical lucidity among research groups.

The relative contributions of biomarkers, disease modifying treatment, and dementia severity to Alzheimer's stigma: A vignette-based experiment.

OBJECTIVE: The symptoms and prognosis of Alzheimer's disease (AD) dementia contribute to the public's negative reactions toward individuals with AD dementia and their families. But what if, using AD biomarker tests, diagnosis was made before the onset of dementia, and a disease-modifying treatment was available? This study tests the hypotheses that a "preclinical" diagnosis of AD and treatment that improves prognosis will mitigate stigmatizing reactions. METHODS: A sample of U.S. adults were randomized to receive one vignette created by a 3 × 2 × 2 vignette-based experiment that described a person with varied clinical symptom severity (Clinical Dementia Rating stages 0 (no dementia), 1 (mild), or 2 (moderate)), AD biomarker test results (positive vs negative), and disease-modifying treatment (available vs not available). Between-group comparisons were conducted of scores on the Modified Family Stigma in Alzheimer's Disease Scale (FS-ADS). RESULTS: The sample of 1,817 adults had a mean age two years younger than that of U.S. adults but was otherwise similar to the general adult population. The response rate was 63% and the completion rate was 96%. In comparisons of randomized groups, mild and moderate symptoms of dementia evoked stronger reactions on all FS-ADS domains compared to no dementia (all p < 0.001). A positive biomarker test result evoked stronger reactions on all but one FS-ADS domain (negative aesthetic attributions) compared to a negative biomarker result (all p < 0.001). Disease-modifying treatment had no measurable influence on stigma (all p > 0.05). CONCLUSIONS: The stigmas of dementia spill over into preclinical AD, and availability of treatment does not alter that stigma. Translation of the preclinical AD construct from research into practice will require interventions that mitigate AD stigma to preserve the dignity and identity of individuals living with AD.

Disclosing Genetic Risk of Alzheimer's Disease to Cognitively Unimpaired Older Adults: Findings from the Study of Knowledge and Reactions to APOE Testing (SOKRATES II).

BACKGROUND: Current practice guidelines recommend against Apolipoprotein E (APOE) testing. However, advances in Alzheimer's disease (AD) research and care may soon change this. OBJECTIVE: To examine longitudinally the experience of learning an APOE result and, if an ɛ4 carrier, taking a disease-specific treatment to reduce one's risk of AD. METHODS: Fifty ɛ4 carriers and 20 non-carriers completed semi-structured interviews 3 months and 15 months after APOE disclosure. RESULTS: Individuals generally understand their APOE results. While non-carriers felt relief, ɛ4 carriers often described themselves as disappointed by their result but nevertheless glad to know. Carriers expressed concerns about stigma and discrimination, including in the workplace. Carriers adopted new health behaviors at higher rates than non-carriers and revised their future plans to account for their increased risk of AD. Individuals participating in research were hopeful that their participation would help them or others; individuals who learned they were at increased risk for AD but who could not participate in research were disappointed. CONCLUSION: Providers disclosing APOE results should be sensitive to how APOE results shape emotions, self-perceptions, and attitudes about memory; raise concerns about stigma and discrimination in personal and professional relationships; influence health behaviors and decision-making; and can have follow-on effects on family members.