Qualitative Message Development to Motivate Quitting Smoking in Older Adults: Dementia May Motivate Quitting.

Compared to younger adults, older adults who smoke cigarettes are half as likely to make a quit attempt, but more likely to maintain abstinence using evidence-based smoking treatments (EBSTs), illustrating the need for motivational messages to promote cessation through EBSTs. It is unclear whether messaging regarding the association between smoking and dementia might motivate older adults to quit. We conducted 90-min semi-structured qualitative interviews and surveys via telephone with 24 U.S. older adults who smoke (ages 50-75) with no cognitive impairment history. Rapid content analysis revealed the most reported health-related concern of aging was dementia/cognitive loss/loss of functioning. However, most participants were unaware of the association between cognitive decline and smoking. Participants had seen previous smoking cessation advertisements, but most did not feel motivated to quit by them. The majority found a message about smoking raising dementia risk and quitting decreasing that risk to be motivational for cessation. Exact message content preference varied, but 2 broad categories arose: hope- and fear-based messages. Most participants stated willingness to use some cessation pharmacotherapy and half were willing to use cessation counseling. Participants preferred messages to come from older adults who were successful quitters. To our knowledge, this was the first study to explore potential motivational messages targeting older adult smokers, including the potential acceptability of a dementia-related message in this context. This work supports patient desire for targeted motivational messages for older adult smokers. Messages highlighting the link between smoking and dementia are perceived to be motivational for this group; future work should compare a hope- to fear-based messages.

Longitudinal normative standards for cognitive tests and composites using harmonized data from two Wisconsin AD-risk-enriched cohorts.

INTRODUCTION: Published norms are typically cross-sectional and often are not sensitive to preclinical cognitive changes due to dementia. We developed and validated demographically adjusted cross-sectional and longitudinal normative standards using harmonized outcomes from two Alzheimer's disease (AD) risk-enriched cohorts. METHODS: Data from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center were combined. Quantile regression was used to develop unconditional (cross-sectional) and conditional (longitudinal) normative standards for 18 outcomes using data from cognitively unimpaired participants (N = 1390; mean follow-up = 9.25 years). Validity analyses (N = 2456) examined relationships between percentile scores (centiles), consensus-based cognitive statuses, and AD biomarker levels. RESULTS: Unconditional and conditional centiles were lower in those with consensus-based impairment or biomarker positivity. Similarly, quantitative biomarker levels were higher in those whose centiles suggested decline. DISCUSSION: This study presents normative standards for cognitive measures sensitive to pre-clinical changes. Future directions will investigate potential clinical applications of longitudinal normative standards. HIGHLIGHTS: Quantile regression was used to construct longitudinal norms for cognitive tests. Poorer percentile scores were related to concurrent diagnosis and Alzheimer's disease biomarkers. A ShinyApp was built to display test scores and norms and flag low performance.

Ethnoracialized group differences in attitudes and knowledge about schizophrenia and willingness to engage in biomarker research: The UBIGR Study.

Although there is renewed optimism in biomarker research in schizophrenia, there is also need for greater inclusion of historically underrepresented groups in the research. In the present study, we surveyed 599 African American, 352 American Indian/Alaska Native, and 725 NonHispanic White participants about their attitudes toward research, knowledge and attitudes about schizophrenia, and willingness to engage in biomarker testing. Attitudes toward research were examined using the standardized 7-item Research Attitudes Questionnaire (RAQ) measure. Using structural equation modeling (SEM), we tested our predictive model of the likelihood of willingness to engage in biomarker testing for schizophrenia risk. Members of historically underrepresented groups were less willing to engage in biomarker testing. Overall, attitudes toward research, particularly trust, influenced biomarker testing willingness. These findings suggest that factors influencing willingness to engage in schizophrenia biomarker testing may be modifiable by outreach engagement and education.

Relationships of Cognitive Measures with Cerebrospinal Fluid but Not Imaging Biomarkers of Alzheimer Disease Vary between Black and White Individuals.

OBJECTIVE: Biomarkers of Alzheimer disease vary between groups of self-identified Black and White individuals in some studies. This study examined whether the relationships between biomarkers or between biomarkers and cognitive measures varied by racialized groups. METHODS: Cerebrospinal fluid (CSF), amyloid positron emission tomography (PET), and magnetic resonance imaging measures were harmonized across four studies of memory and aging. Spearman correlations between biomarkers and between biomarkers and cognitive measures were calculated within each racialized group, then compared between groups by standard normal tests after Fisher's Z-transformations. RESULTS: The harmonized dataset included at least one biomarker measurement from 495 Black and 2,600 White participants. The mean age was similar between racialized groups. However, Black participants were less likely to have cognitive impairment (28% vs 36%) and had less abnormality of some CSF biomarkers including CSF Aß42/40, total tau, p-tau181, and neurofilament light. CSF Aß42/40 was negatively correlated with total tau and p-tau181 in both groups, but at a smaller magnitude in Black individuals. CSF Aß42/40, total tau, and p-tau181 had weaker correlations with cognitive measures, especially episodic memory, in Black than White participants. Correlations of amyloid measures between CSF (Aß42/40, Aß42) and PET imaging were also weaker in Black than White participants. Importantly, no differences based on race were found in correlations between different imaging biomarkers, or in correlations between imaging biomarkers and cognitive measures. INTERPRETATION: Relationships between CSF biomarkers but not imaging biomarkers varied by racialized groups. Imaging biomarkers performed more consistently across racialized groups in associations with cognitive measures. ANN NEUROL 2024;95:495-506.

Cardiometabolic outcomes in Kronos Early Estrogen Prevention Study continuation: 14-year follow-up of a hormone therapy trial.

OBJECTIVE: This study aimed to determine long-term cardiometabolic effects of hormone therapies initiated within 3 years of onset of menopause after a 14-year follow-up study of participants of the Kronos Early Estrogen Prevention Study (KEEPS). METHODS: KEEPS was a multisite clinical trial that recruited recently menopausal women with good cardiovascular health for randomization to oral conjugated equine estrogens (Premarin, 0.45 mg/d) or transdermal 17ß-estradiol (Climara, 50 µg/d) both with micronized progesterone (Prometrium, 200 mg/d) for 12 d/mo, or placebo pills and patch for 4 years. KEEPS continuation recontacted KEEPS participants 14 years after randomization and 10 years after the completion of the 4-year clinical trial to attend in-person clinic visits. RESULTS: Participants of KEEPS continuation (n = 299 of the 727 KEEPS participants; 41%) had an average age of 67 years (range, 58-73 y). Measurements of systolic and diastolic blood pressures, waist-to-hip ratio, fasting levels of glucose, insulin, lipid profiles, and homeostasis model assessment of insulin resistance were not different among the treatment groups at either KEEPS baseline or at KEEPS continuation visits, or for change between these two visits. The frequency of self-reported diabetes ( P = 0.007) and use of diabetes medications was higher in the placebo than the oral conjugated equine estrogens ( P = 0.045) or transdermal 17ß-estradiol ( P = 0.02) groups, but these differences were not supported by the laboratory measurements of glycemia or insulin resistance. CONCLUSIONS: There was no evidence of cardiovascular and/or metabolic benefits or adverse effects associated with 4 years use of oral or transdermal forms of hormone therapy by recently menopausal women with good cardiovascular health after 10 years.

Associations of sleep duration and daytime sleepiness with plasma amyloid beta and cognitive performance in cognitively unimpaired, middle-aged and older African Americans.

STUDY OBJECTIVES: Given the established racial disparities in both sleep health and dementia risk for African American populations, we assess cross-sectional and longitudinal associations of self-report sleep duration (SRSD) and daytime sleepiness with plasma amyloid beta (Aß) and cognition in an African American (AA) cohort. METHODS: In a cognitively unimpaired sample drawn from the African Americans Fighting Alzheimer's in Midlife (AA-FAiM) study, data on SRSD, Epworth Sleepiness Scale, demographics, and cognitive performance were analyzed. Aß40, Aß42, and the Aß42/40 ratio were quantified from plasma samples. Cross-sectional analyses explored associations between baseline predictors and outcome measures. Linear mixed-effect regression models estimated associations of SRSD and daytime sleepiness with plasma Aß and cognitive performance levels and change over time. RESULTS: One hundred and forty-seven participants comprised the cross-sectional sample. Baseline age was 63.2 ±â€…8.51 years. 69.6% self-identified as female. SRSD was 6.4 ±â€…1.1 hours and 22.4% reported excessive daytime sleepiness. The longitudinal dataset included 57 participants. In fully adjusted models, neither SRSD nor daytime sleepiness is associated with cross-sectional or longitudinal Aß. Associations with level and trajectory of cognitive test performance varied by measure of sleep health. CONCLUSIONS: SRSD was below National Sleep Foundation recommendations and daytime sleepiness was prevalent in this cohort. In the absence of observed associations with plasma Aß, poorer self-reported sleep health broadly predicted poorer cognitive function but not accelerated decline. Future research is necessary to understand and address modifiable sleep mechanisms as they relate to cognitive aging in AA at disproportionate risk for dementia. CLINICAL TRIAL INFORMATION: Not applicable.

Anticipated Psychological or Behavioral Reactions to Learning Alzheimer Biomarker Results: Associations With Contextual Factors.

BACKGROUND: As Alzheimer disease (AD) biomarker testing becomes more widely available, adults may opt to learn results. Considering potential reactions to learning biomarker results can guide prebiomarker and postbiomarker testing education and counseling programs. METHODS: Cognitively healthy adults enrolled in observational Alzheimer research responded to a telephone survey about learning AD risk information (n=334; 44% Black or African American; mean age=64.9±7.0). Multiple linear regression models tested if contextual factors predicted anticipated psychological impact (distress, stigma, and cognitive symptoms) or behavior change (planning and risk-reduction). Secondary analyses tested for differences in relationships by racial identity. RESULTS: Internal health locus of control, concern about AD, self-identified sex, education, family dementia history, and belief in AD modifiability predicted anticipated psychological impact. Concern about AD, age, racial identity, belief in AD modifiability, research attitudes, and exposure to brain health-related social norms predicted anticipated behavior change. For Black respondents, there were no sex differences in anticipated distress, whereas there were stronger relationships between health locus of control, brain health social norms, and education on outcomes compared with White respondents. CONCLUSIONS: Results may inform personalized and culturally tailored biomarker testing education and counseling to minimize psychological impacts and increase behavior change related to learning AD risk information.

Plasma Aß42/40 and cognitive variability are associated with cognitive function in Black Americans: Findings from the AA-FAIM cohort.

Introduction: It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low-burden disease markers, plasma amyloid beta (Aß)42/40, and intra-individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults. Methods: Two hundred fifty-seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA-FAIM) study underwent at least one cognitive assessment visit; a subset of n = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants' z scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma Aß42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aß42/40. Results: IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aß42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low Aß42/40 was associated with faster cognitive declines over time. Discussion: Our results are promising as they extend existing findings to an Black American sample using low-cost, low-burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.

The importance of the dyad: Participant perspectives on sharing biomarker results in Alzheimer's disease research.

BACKGROUND: In the asymptomatic "preclinical" phase of Alzheimer's disease (AD), abnormal biomarkers indicate risk for developing cognitive impairment. Biomarker information is increasingly being disclosed to participants in research settings, and biomarker testing and results disclosure will be implemented in clinical settings in the future. Biomarker disclosure has potential psychosocial benefits and harms, impacting affected individuals and their support person(s). Limited data are available about with whom research participants share their results, information that will be necessary to develop disclosure protocols and post-disclosure resources. Additionally, existing research has been conducted in largely White cohorts, limiting applicability to future clinical populations. METHODS: We enrolled a diverse cohort of 329 adults (184 non-Hispanic White and 145 Black/African American individuals) who previously participated in AD research. After reviewing a vignette describing a hypothetical biomarker research study, participants indicated their anticipated willingness to share biomarker results with loved ones, and what reactions they anticipated from others. Using mixed-methods analysis, we identified responses related to willingness to share results. RESULTS: A majority (78.7%) were willing to share their results with support persons. Many (59.6%) felt it would not be difficult to share, and most (90.6%) believed their loved ones would be supportive. The most common reasons for sharing were to prepare for possible future AD (41.0% of respondents), while the most common reason for not sharing was to avoid worrying loved ones (4.8% of respondents). A total of 7.3% of respondents related reasons regarding being unsure about sharing. DISCUSSION: Participants' interest in sharing results supports integrating support persons into AD biomarker research, and may help maximize potential benefits for participants. Communicating with this "dyad" of research participant and support person(s) may improve involvement in research, and help prepare for implementation of clinical biomarker testing by clarifying communication preferences and the influence of support persons on psychosocial outcomes.

Association of Age at Menopause and Hormone Therapy Use With Tau and ß-Amyloid Positron Emission Tomography.

Importance: Postmenopausal females represent around 70% of all individuals with Alzheimer disease. Previous literature shows elevated levels of tau in cognitively unimpaired postmenopausal females compared with age-matched males, particularly in the setting of high ß-amyloid (Aß). The biological mechanisms associated with higher tau deposition in female individuals remain elusive. Objective: To examine the extent to which sex, age at menopause, and hormone therapy (HT) use are associated with regional tau at a given level of Aß, both measured with positron emission tomography (PET). Design, Setting, and Participants: This cross-sectional study included participants enrolled in the Wisconsin Registry for Alzheimer Prevention. Cognitively unimpaired males and females with at least 1 18F-MK-6240 and 11C-Pittsburgh compound B PET scan were analyzed. Data were collected between November 2006 and May 2021. Exposures: Premature menopause (menopause at younger than 40 years), early menopause (menopause at age 40-45 years), and regular menopause (menopause at older than 45 years) and HT user (current/past use) and HT nonuser (no current/past use). Exposures were self-reported. Main Outcomes and Measures: Seven tau PET regions that show sex differences across temporal, parietal, and occipital lobes. Primary analyses examined the interaction of sex, age at menopause or HT, and Aß PET on regional tau PET in a series of linear regressions. Secondary analyses investigated the influence of HT timing in association with age at menopause on regional tau PET. Results: Of 292 cognitively unimpaired individuals, there were 193 females (66.1%) and 99 males (33.9%). The mean (range) age at tau scan was 67 (49-80) years, 52 (19%) had abnormal Aß, and 106 (36.3%) were APOEε4 carriers. There were 98 female HT users (52.2%) (past/current). Female sex (standardized ß = -0.41; 95% CI, -0.97 to -0.32; P < .001), earlier age at menopause (standardized ß = -0.38; 95% CI, -0.14 to -0.09; P < .001), and HT use (standardized ß = 0.31; 95% CI, 0.40-1.20; P = .008) were associated with higher regional tau PET in individuals with elevated Aß compared with male sex, later age at menopause, and HT nonuse. Affected regions included medial and lateral regions of the temporal and occipital lobes. Late initiation of HT (>5 years following age at menopause) was associated with higher tau PET compared with early initiation (ß = 0.49; 95% CI, 0.27-0.43; P = .001). Conclusions and Relevance: In this study, females exhibited higher tau compared with age-matched males, particularly in the setting of elevated Aß. In females, earlier age at menopause and late initiation of HT were associated with increased tau vulnerability especially when neocortical Aß elevated. These observational findings suggest that subgroups of female individuals may be at higher risk of pathological burden.

Associations between self-reported sleep patterns and health, cognition and amyloid measures: results from the Wisconsin Registry for Alzheimer's Prevention.

Previous studies suggest associations between self-reported sleep problems and poorer health, cognition, Alzheimer's disease pathology and dementia-related outcomes. It is important to develop a deeper understanding of the relationship between these complications and sleep disturbance, a modifiable risk factor, in late midlife, a time when Alzheimer's disease pathology may be accruing. The objectives of this study included application of unsupervised machine learning procedures to identify distinct subgroups of persons with problematic sleep and the association of these subgroups with concurrent measures of mental and physical health, cognition and PET-identified amyloid. Dementia-free participants from the Wisconsin Registry for Alzheimer's Prevention (n = 619) completed sleep questionnaires including the Insomnia Severity Index, Epworth Sleepiness Scale and Medical Outcomes Study Sleep Scale. K-means clustering analysis identified discrete sleep problem groups who were then compared across concurrent health outcomes (e.g. depression, self-rated health and insulin resistance), cognitive composite indices including episodic memory and executive function and, in a subset, Pittsburgh Compound B PET imaging to assess amyloid burden. Significant omnibus tests (P < 0.05) were followed with pairwise comparisons. Mean (SD) sample baseline sleep assessment age was 62.6 (6.7). Cluster analysis identified three groups: healthy sleepers [n = 262 (42.3%)], intermediate sleepers [n = 229 (37.0%)] and poor sleepers [n = 128 (20.7%)]. All omnibus tests comparing demographics and health measures across sleep groups were significant except for age, sex and apolipoprotein E e4 carriers; the poor sleepers group was worse than one or both of the other groups on all other measures, including measures of depression, self-reported health and memory complaints. The poor sleepers group had higher average body mass index, waist-hip ratio and homeostatic model assessment of insulin resistance. After adjusting for covariates, the poor sleepers group also performed worse on all concurrent cognitive composites except working memory. There were no differences between sleep groups on PET-based measures of amyloid. Sensitivity analyses indicated that while different clustering approaches resulted in different group assignments for some (predominantly the intermediate group), between-group patterns in outcomes were consistent. In conclusion, distinct sleep characteristics groups were identified with a sizable minority (20.7%) exhibiting poor sleep characteristics, and this group also exhibited the poorest concurrent mental and physical health and cognition, indicating substantial multi-morbidity; sleep group was not associated with amyloid PET estimates. Precision-based management of sleep and related factors may provide an opportunity for early intervention that could serve to delay or prevent clinical impairment.

Effect of Metabolic Syndrome Risk Factors on Processing Speed and Executive Function in Three Racialized Groups.

BACKGROUND: Metabolic syndrome (MetS) has been associated with increased risk for Alzheimer's disease and related dementias (ADRD). Understanding the association of MetS risk factors to processing speed and executive function in the pre-clinical stages of ADRD in under-represented groups would offer insight on potential mechanisms through which MetS associates with ADRD risk. OBJECTIVE: Examine association of MetS features and processing speed and executive function across three racial groups. METHODS: Cognitively unimpaired adults from the Wisconsin Alzheimer's Disease Research Center and the Wisconsin Registry for Alzheimer's Disease Prevention completed blood-draws and neuropsychological testing. Six cognitive outcomes were assessed in association to MetS risk factors: Trailmaking Tests A and B, Animal Fluency, Digit Symbol, and composite scores for Processing Speed and Executive Function. Linear mixed effect models were used to assess the relationship between MetS risk factor count and longitudinal cognitive performance across three racialized groups. RESULTS: Participant sample sizes varied by outcome analyzed (N = 714-1,088). African American and Native American groups exhibited higher rates of MetS than non-Hispanic Whites. MetS was associated with processing speed and executive function across all racialized groups. Three-way interaction by racialized group was limited to one cognitive outcome: Trailmaking Test A. CONCLUSION: Metabolic dysfunction incrementally affects cognitive trajectory, with generally similar associations across racial groups. Since racialized groups exhibit higher levels of both MetS and ADRD, MetS may represent a driving factor for increased ADRD risk experience by racialized group and an important and modifiable target through which to reduce risk of ADRD.

Associations between pituitary-ovarian hormones and cognition in recently menopausal women independent of type of hormone therapy.

OBJECTIVES: To examine associations of pituitary-ovarian hormone levels with cognition before and after different formulations of hormone therapy (HT) or placebo independent of treatment group. METHODS: Recently menopausal, healthy women were randomized to 0.45 mg/day oral conjugated equine estrogens (o-CEE, n = 109), 50 µg/day transdermal 17ß (tE2, n = 107) or placebo pills and patches (n = 146); women on active treatment received oral 200 mg/day micronized progesterone for 12 days per month. Levels of estrone, 17ß-estradiol, follicle stimulating hormone, luteinizing hormone, androstenedione, and testosterone were determined prior to and after 48 months of study participation. Neuropsychological testing was administered at baseline, and months 18, 36 and 48. Latent growth curve models controlling for education level, age, APOE allele status, waist circumference, and treatment examined the trajectories of each cognitive domain after accounting for the effect of hormone levels at baseline and months 18, 36 and 48. A linear multivariate mixed model examined the effect of changes in hormone levels on changes in trajectories of complex attention tasks with varying degrees of difficulty. RESULTS: All women were adherent to treatment at month 48. Higher baseline estrone levels were associated with poorer global cognition, auditory attention and working memory, visual attention, and executive function, but not working memory. Higher levels of baseline 17ß-E2 were associated with poorer cognitive performance, with marginal significance at baseline in speeded language and mental flexibility (p = 0.013). Other hormone levels were not associated with cognition. Controlling for all treatments, hormone levels at baseline and at month 48 did not have any significant correlation with cognitive trajectories over time. SUMMARY: In healthy, recently menopausal women, baseline estrone levels were inversely associated with selected cognitive factors independent of two types of HT or placebo during 4 years of follow-up. Baseline levels of the other pituitary-ovarian hormones studied were not associated with baseline cognition, nor were changes in any hormones associated with changes in cognition during the study. The marginal association between estradiol levels and cognitive factors warrants further investigation. GOV NUMBERS: NCT00154180, NCT00623311.

Wisconsin Healthcare Utilization Cost Among American Indians/Alaska Natives with and without Alzheimer's Disease and Related Dementias.

Individuals with Alzheimer's disease and related dementias (ADRD) accrue higher healthcare utilization costs than peers without ADRD, but incremental costs of ADRD among American Indians/Alaska Natives (AI/AN) is unknown. State-wide paid electronic health record data were retrospectively analyzed using percentile-based bootstrapped 95% confidence intervals of the weighted mean difference of total 5-year billed costs to compare total accrued for non-Tribal and Indian Health Service utilization costs among Medicaid and state program eligible AI/AN, ≥40 years, based on the presence/absence of ADRD (matching by demographic and medical factors). AI/AN individuals with ADRD accrued double the costs compared to those without ADRD, costing an additional $880.45 million to $1.91 billion/year.

The Advisory Group on Risk Evidence Education for Dementia: Multidisciplinary and Open to All.

The brain changes of Alzheimer's disease and other degenerative dementias begin long before cognitive dysfunction develops, and in people with subtle cognitive complaints, clinicians often struggle to predict who will develop dementia. The public increasingly sees benefits to accessing dementia risk evidence (DRE) such as biomarkers, predictive algorithms, and genetic information, particularly as this information moves from research to demonstrated usefulness in guiding diagnosis and clinical management. For example, the knowledge that one has high levels of amyloid in the brain may lead one to seek amyloid reducing medications, plan for disability, or engage in health promoting behaviors to fight cognitive decline. Researchers often hesitate to share DRE data, either because they are insufficiently validated or reliable for use in individuals, or there are concerns about assuring responsible use and ensuring adequate understanding of potential problems when one's biomarker status is known. Concerns include warning people receiving DRE about situations in which they might be compelled to disclose their risk status potentially leading to discrimination or stigma. The Advisory Group on Risk Evidence Education for Dementia (AGREEDementia) welcomes all concerned with how best to share and use DRE. Supporting understanding in clinicians, stakeholders, and people with or at risk for dementia and clearly delineating risks, benefits, and gaps in knowledge is vital. This brief overview describes elements that made this group effective as a model for other health conditions where there is interest in unfettered collaboration to discuss diagnostic uncertainty and the appropriate use and communication of health-related risk information.

Subjective Cognitive Decline Associated with Discrimination in Medical Settings among Transgender and Nonbinary Older Adults.

BACKGROUND: Transgender and nonbinary (TNB) individuals report greater subjective cognitive decline (SCD) compared to non-TNB people. SCD involves self-reported problems with memory and thinking and is a potential risk for Alzheimer's disease and related dementias (ADRD). We explored psychosocial factors, such as discrimination in medical settings, associated with SCD in a sample of TNB older adults. METHODS: We utilized cross-sectional data on aging health, SCD (memory complaints and worsening memory in the past year), and discrimination in medical settings from The PRIDE Study for LGBTQ+ adults aged 50+ including TNB adults (n = 115). Associations were tested using multivariate logistic regression. RESULTS: Nearly 16% of TNB participants rated their memory as poor/fair, and 17% reported that their memory was worse than a year ago. TNB older adults with SCD were more likely to report experiencing discrimination in medical settings. After adjustment, those reporting discrimination in medical settings had 4.5 times higher odds of reporting worsening memory than those who did not (OR: 4.5; 95%-CI: 1.5-13.2; p = 0.006), and 7.5 times more likely to report poor/fair memory (OR: 7.49; 95%-CI: 1.7-32.8; p = 0.008); Conclusions: TNB older adults reported high frequencies of SCD and discrimination in medical settings. Further research exploring affirmative cognitive screening and healthcare services is needed.

Psychological well-being and cognitive aging in Black, Native American, and White Alzheimer's Disease Research Center participants.

Psychological well-being is associated with cognition in later life but has not been examined across diverse populations-including minoritized communities at disproportionately high risk of dementia. Further, most previous work has not been able to examine links between specific facets of psychological well-being and performance within distinct cognitive domains that can capture subclinical impairment. Using a well-characterized sample followed through enrollment in an NIH-funded Alzheimer's Disease Center, we sought to test these associations within three racial groups at baseline. Participants were N = 529 cognitively unimpaired Black, American Indian/Alaska Native (AI/AN), and white middle-aged and older adults (mean age = 63.6, SD = 8.1, range = 45-88 years) enrolled in the Wisconsin Alzheimer's Disease Research Center's Clinical Core. Predictors included validated NIH Toolbox Emotion Battery scales assessing positive affect, general life satisfaction, and meaning and purpose. Outcomes included performance on widely used tests of executive functioning and episodic memory. We conducted race-stratified regression models to assess within-group relationships. Black and AI/AN participants reported lower life satisfaction than white participants. Racial disparities were not observed for positive affect or meaning and purpose scores. Across groups, life satisfaction predicted better executive functioning. Similar associations were observed for positive affect in Black and AI/AN samples but not among whites. In general, well-being measures were not related to performance on tests of episodic memory. Our results highlight well-being as a potentially important determinant of late-life cognitive health, particularly executive functioning, that is modifiable if older adults are connected with appropriate resources and supports. Further, psychological well-being may represent a potent target for brain health interventions tailored for Black and Native communities.

Implications of preclinical Alzheimer's disease biomarker disclosure for US policy and society.

Disclosure of Alzheimer's disease (AD) biomarkers to cognitively unimpaired adults are currently conducted only in research settings. Yet, US Food and Drug Administration approval of a disease-modifying treatment for symptomatic individuals, improved understanding of the "preclinical" phase of disease, and advancements toward more accessible biomarker tests suggest such disclosure will increase in frequency, eventually becoming routine in clinical practice. The changing landscape in AD research to focus on biomarkers has generated debate on the validity and clinical utility of disclosure to cognitively unimpaired adults. This article explores the broader social implications of more widespread AD biomarker disclosure-that is, of individuals learning their risk for developing dementia caused by AD. We identify 10 challenges and offer preliminary solutions. As the field continues to evolve, it is essential to anticipate and address these broader ethical, legal, and social implications of disclosure.

Racial Differences in Associations of Cognitive Health Status With Happiness, Helplessness, and Hopelessness Among Older Adults: An Exploratory Study.

Background: The relationship between healthy and positive aging and dementia and cognitive impairment has received limited attention in the field of aging. Affect impacts cognitive changes and processes, and cognitive impairment is associated with affective comorbidities. The purpose of the study was to examine (a) whether happiness, helplessness, and hopelessness are linked to cognitive health status, and (b) whether these associations differ by race. Methods: Participants were enrollees in the Wisconsin Alzheimer's Disease Research Center's Clinical Core (ADRC). Average age at baseline was 60.85 (SD = 8.65), 73.70 (SD = 8.02), and 73.80 (SD = 9.59) years for cognitively normal individuals, individuals with MCI, and individuals with dementia, respectively. Results: In the full sample, chi-square test results revealed associations between Cognitive Health Status (CHS) and (a) happiness, χ2(2) = 6.06, p < 0.05, (b) helplessness, χ2(2) = 6.44, p < 0.05, and (c) hopelessness, χ2(2) = 14.11, p < 0.01. Conclusion: This study provides support for the association of both positive and negative affect with cognitive health status in middle- to older-aged adults.

Anticipated reactions to learning Alzheimer's disease biomarker results.

INTRODUCTION: We developed the Alzheimer's Biomarker Survey to assess willingness to enroll in biomarker studies that disclose results and anticipated reactions to an elevated biomarker result. METHODS: Participants included cognitively unimpaired adults enrolled in longitudinal AD studies (n = 334, mean age = 64.8 ± 7.7, 44% non-Hispanic Black or African American). Exploratory and confirmatory factor analyses determined the latent structure comprising anticipated reactions to learning AD biomarker results. Measurement invariance was tested across racial groups. RESULTS: Two models comprising behavior change and psychological impact fit well for the total sample and the two racial groups. The 2-factor behavior change model assessed constructs of planning and dementia risk-reduction. The 3-factor psychological impact model assessed constructs of distress, cognitive symptoms, and stigma. Both models exhibited measurement invariance across racial groups. DISCUSSION: The 28-item Anticipated Reactions to AD Biomarker Disclosure scale is a reliable and valid measure of anticipated reactions when communicating AD biomarker results to research participants.