A survey study of Alzheimer's stigma among Black adults: intersectionality of Black identity and biomarker diagnosis.

OBJECTIVE: We urgently need to understand Alzheimer's disease (AD) stigma among Black adults. Black communities bear a disproportionate burden of AD, and recent advances in early diagnosis using AD biomarkers may affect stigma associated with AD. The goal of our study is to characterize AD stigma within our cohort of self-identified Black participants and test how AD biomarker test results may affect this stigma. DESIGN: We surveyed a sample of 1,150 self-identified Black adults who were randomized to read a vignette describing a fictional person, who was described as either having a positive or negative biomarker test result. After reading the vignette, participants completed the modified Family Stigma in Alzheimer's Disease Scale (FS-ADS). We compared FS-ADS scores between groups defined by age, gender, and United States Census region. We examined interactions between these groupings and AD biomarker test result. RESULTS: Participants over age 65 had lower scores (lower stigma) on all 7 FS-ADS domains compared to those under 65: structural discrimination, negative severity attributions, negative aesthetic attributions, antipathy, support, pity, and social distance. In the biomarker positive condition, worries about structural discrimination were greater than in the biomarker negative condition and statistically similar in the two age groups (DOR, 0.39 [95%CI, 0.22-0.69]). This pattern of results was similar for negative symptom attributions (DOR, 0.51 [95%CI, 0.28-0.90]). CONCLUSION: While older adults reported less AD stigma than younger adults, AD biomarker testing caused similarly high concerns about structural discrimination and negative severity attributions. Thus, use of AD biomarker diagnosis may increase AD stigma and exacerbate healthcare disparities known to effect AD diagnosis in some Black adults. Advances in AD diagnosis may interact with social and structural factors to differentially affect groups of Black adults.

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 June 11and July 3, 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 < .001). A positive result correlates with stronger reactions on 6 of 7 FS-ADS domains (all p < .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.

Sex, gender, sexual orientation, and more: Sexual diversity in Alzheimer's research needs a new lens to achieve inclusive research and generalizable results.

Diversity, Equity, and Inclusion (DEI) efforts in Alzheimer's disease and related dementia (ADRD) research are guiding the adoption of two-step self-report questions that capture research participants' identity based on categories of sex, sexual orientation, and gender identity. The intent is to facilitate inclusion and representation of sexual and gender minoritized (SGM) communities in ADRD research. The data from using these questions are on a collision course with another National Institute of Aging initiative, which is aimed at understanding sex differences in ADRD mechanisms. Here, we critically analyze the goals and methods of the two initiatives. We propose that, in addition to being SGM focused, DEI efforts are needed to expand how scientists consider and measure sexual diversity itself. Highlights: Sex, sexual orientation, and gender identity (SSOGI) will be asked in ADRD studies.SSOGI data will expand representation of research participant identities.SSOGI data are on a collision course with sex differences research.Both emphasize sexual diversity (SD) largely as SSOGI identity categories.Diversity, Equity, and Inclusion efforts must develop SD methods in ADRD research.

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.

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.

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.

Sex modifies effects of imaging and CSF biomarkers on cognitive and functional outcomes: a study of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. Two of 3 patients with AD are biologically female; therefore, the biological underpinnings of this diagnosis disparity may inform interventions slowing the AD progression. To bridge this gap, we conducted analyses of 1078 male and female participants from the Alzheimer's Disease Neuroimaging Initiative to examine associations between levels of cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes. The Chow test was used to quantify sex differences by determining if biological sex affects relationships between the studied biomarkers and outcomes. Multiple magnetic resonance imaging (whole brain, entorhinal cortex, middle temporal gyrus, fusiform gyrus, hippocampus), position emission tomography (AV45), and CSF (P-TAU, TAU) biomarkers were differentially associated with cognitive and functional outcomes. Post-hoc bootstrapped and association analyses confirmed these differential effects and emphasized the necessity of using separate, sex-stratified models. The studied imaging/CSF biomarkers may account for some of the sex-based variation in AD pathophysiology. The identified sex-varying relationships between CSF/imaging biomarkers and cognitive/functional outcomes warrant future biological investigation in independent cohorts.

"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.

Epigenetic age and socioeconomic status contribute to racial disparities in cognitive and functional aging between Black and White older Americans.

Epigenetic age, a biological aging marker measured by DNA methylation, is a potential mechanism by which social factors drive disparities in age-related health. Epigenetic age gap is the residual between epigenetic age measures and chronological age. Previous studies showed associations between epigenetic age gap and age-related outcomes including cognitive capacity and performance on some functional measures, but whether epigenetic age gap contributes to disparities in these outcomes is unknown. We use data from the Health and Retirement Study to examine the role of epigenetic age gap in racial disparities in cognitive and functional outcomes and consider the role of socioeconomic status (SES). Epigenetic age measures are GrimAge or Dunedin Pace of Aging methylation (DPoAm). Cognitive outcomes are cross-sectional score and two-year change in Telephone Interview for Cognitive Status (TICS). Functional outcomes are prevalence and incidence of limitations performing Instrumental Activities of Daily Living (IADLs). We find, relative to White participants, Black participants have lower scores and greater decline in TICS, higher prevalence and incidence rates of IADL limitations, and higher epigenetic age gap. Age- and gender-adjusted analyses reveal that higher GrimAge and DPoAm gap are both associated with worse cognitive and functional outcomes and mediate 6-11% of racial disparities in cognitive outcomes and 19-39% of disparities in functional outcomes. Adjusting for SES attenuates most DPoAm associations and most mediation effects. These results support that epigenetic age gap contributes to racial disparities in cognition and functioning and may be an important mechanism linking social factors to disparities in health outcomes.

Time out weekly smile: A pilot test of a virtual respite program.

Respite care provides alternative care for persons living with dementia (PLWD) and is intended to alleviate the burden of caregiving. However, the evaluation of respite programs is limited. Time Out Weekly Smile (TOWS) is a virtual intergenerational respite care program designed to meet the needs of PLWD and their care partners and provide allied health students opportunities to serve as respite volunteers. This multi-method pilot study aimed to evaluate the experience of TOWS participation for all (i.e., care partners, PLWD, students) and identify outcomes of interest for future efficacy studies. Semi-structured interviews with all participants after experiencing TOWS were analyzed using conventional content analysis methods and student surveys of dementia attitudes were summarized. Results demonstrated lasting mutual benefits for all participants including social connection and creating meaning. Our findings suggest that including all respite care participants in future efficacy studies will elucidate the wide impact of respite care programs.

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.

The structural and social determinants of Alzheimer's disease related dementias.

INTRODUCTION: The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD. METHODS: In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes. RESULTS: Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper. DISCUSSION: Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research. HIGHLIGHTS: Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.

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+).

Let's Not Repeat History's Mistakes: Two Cautions to Scientists on the Use of Race in Alzheimer's Disease and Alzheimer's Disease Related Dementias Research.

Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) research has advanced gene and biomarker technologies to aid identification of individuals at risk for dementia. This innovation is a lynchpin in development of disease-modifying therapies. The emerging science could transform outcomes for patients and families. However, current limitations in the racial representation and inclusion of racial diversity in research limits the relevance of these technologies: AD/ADRD research cohorts used to define biomarker cutoffs are mostly White, despite clinical and epidemiologic research that shows Black populations are among those experiencing the greatest burdens of AD/ADRD. White cohorts alone are insufficient to characterize heterogeneity in disease and in life experiences that can alter AD/ADRD's courses. The National Institute on Aging (NIA) has called for increased racial diversity in AD/ADRD research. While scientists are working to implement NIA's plan to build more diverse research cohorts, they are also seeking out opportunities to consider race in AD/ADRD research. Recently, scientists have posed two ways of including race in AD/ADRD research: ancestry-based verification of race and race-based adjustment of biomarker test results. Both warrant careful examination for how they are impacting AD/ADRD science with respect to specific study objectives and the broader mission of the field. If these research methods are not grounded in pursuit of equity and justice, biases they introduce into AD/ADRD science could perpetuate, or even worsen, disparities in AD/ADRD research and care.

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.

Deciding with Others: Interdependent Decision-Making.

Over the course of human life, health care decision-making is often interdependent. In this article, we use "interdependence" to refer to patients' engagement of nonclinicians-for example, family members or trusted friends-to reach health care decisions. Interdependence, we suggest, is common for patients in all stages of life, from early childhood to late adulthood. This view contrasts with the common bioethical assumption that medical decisions are either wholly independent or dependent and that independence or dependence is tightly coupled with a person's decision-making capacity. In this article, we array various approaches to decision-making along a continuum of interdependence. An appreciation of this continuum can empower patients and elucidate ethical challenges that arise when people transition between different kinds of interdependence across the life span.

Research Centers Collaborative Network Workshop on Sex and Gender Differences in Aging.

Aging affects men and women differently; however, the impact of sex and gender on the aging process is not well understood. Moreover, these 2 concepts are often conflated, which further contributes to a lack of clarity on this important issue. In an effort to better understand the relevance of sex and gender in aging research, the Research Centers Collaborative Network sponsored a 1.5-day conference on sex and gender differences in aging that brought together key thought leaders from the 6 National Institute on Aging center programs. The meeting included sessions on comparing males and females, pathophysiological differences, sex/gender in clinical care, and gender and health in the social context. Presenters from a wide array of disciplines identified opportunities for multidisciplinary research to address current gaps in the field and highlighted the need for a more systematic approach to understanding the how and why of sex/gender differences, as well as the health implications of these differences and the sex/gender biases that affect clinical treatment and outcomes. This article summarizes the proceedings of the workshop and provides several recommendations to move the field forward, such as better data collection tools to assess the intersection of sex and gender in epidemiological research; a life course perspective with attention to fetal/developmental origins and key life stages; innovative animal models to distinguish contributions from sex hormones versus sex chromosomes; and integration of sex/gender into teaching and clinical practice. Ultimately, successful implementation of these recommendations will require thoughtful investigations across the translational spectrum and increased collaborations among those with expertise in sex and gender differences.

Patients asking about APOE gene test results? Here's what to tell them.

This guidance can help shape the conversations you have with patients who want to understand the results of their gene and biomarker testing for Alzheimer disease.

Consideration of sex and gender in Alzheimer's disease and related disorders from a global perspective.

Sex or gender differences in the risk of Alzheimer's disease and related dementias (ADRD) differ by world region, suggesting that there are potentially modifiable risk factors for intervention. However, few epidemiological or clinical ADRD studies examine sex differences; even fewer evaluate gender in the context of ADRD risk. The goals of this perspective are to: (1) provide definitions of gender, biologic sex, and sexual orientation. and the limitations of examining these as binary variables; (2) provide an overview of what is known with regard to sex and gender differences in the risk, prevention, and diagnosis of ADRD; and (3) discuss these sex and gender differences from a global, worldwide perspective. Identifying drivers of sex and gender differences in ADRD throughout the world is a first step in developing interventions unique to each geographical and sociocultural area to reduce these inequities and to ultimately reduce global ADRD risk. HIGHLIGHTS: The burden of dementia is unevenly distributed geographically and by sex and gender. Scientific advances in genetics and biomarkers challenge beliefs that sex is binary. Discrimination against women and sex and gender minority (SGM) populations contributes to cognitive decline. Sociocultural factors lead to gender inequities in Alzheimer's disease and related dementias (ADRD) worldwide.