OBJECTIVE:To determine associations between central adiposity, cognitive function, and randomized menopausal hormone therapy (MHT) in a reanalysis of the Kronos Early Estrogen Prevention Study-Cognitive and Affective (KEEPS-Cog) sub-study participants. METHODS:KEEPS randomized 727 women (ages 42-58) who were <36 months postnatural menopause to oral conjugated equine estrogens (o-CEE), transdermal 17-β-estradiol (t-E2), or placebo for 48 months. Participants with diabetes, body mass index >35 kg/m 2 , coronary artery calcium score >50 Agatston Units, and other cardiometabolic disease risk indicators were excluded from enrollment. In the ancillary KEEPS-Cog study, cognitive tests were completed at baseline, 18-, 36-, and 48-month post-randomization. In these analyses, cognitive variables were summarized as four cognitive domain-specific factor scores: verbal learning and memory, auditory attention and working memory, visual attention and executive function, and speeded language and mental flexibility. Waist-hip-ratio (WHR), an indicator of central adiposity, was measured at screening (baseline) and modeled as a covariate in linear latent growth models assessing associations of MHT with cognitive functions at baseline and over time. RESULTS:Higher baseline WHR was associated with poorer performance on all domain-specific cognitive outcomes at baseline and with changes in visual attention and executive function across time. Models including interaction effects were not significant for either o-CEE x WHR or t-E2 x WHR. CONCLUSION:Central adiposity is a risk factor for domain-specific cognitive decline, and thus, cognitive health effects should be investigated in early postmenopausal women, even in women with low cardiovascular risk statuses.

Background Despite significant advances in Alzheimer's disease treatment, underrepresentation of ethnoracialized groups in clinical trials limit the generalizability of study findings. Though mistrust in health care research is a known barrier to clinical trial participation, methods are needed to quantitate this multidimensional subjective term. This study investigated how Black participants view trustworthiness. Objective To provide an overview of participants’ views of a trustworthy study design and investigator. Methods This qualitative study utilized focus group discussions with Black participants 45 years and older. Transcripts were coded by three researchers by means of content analysis. After central categories were identified using concept mapping, we constructed a conceptual model of trust to reflect participants’ views of trustworthiness. Results Participants self-identified as Black, were a mean age of 62, and predominantly female (80%). Focus group analysis revealed that a trustworthy study design and its impact as well as a trustworthy investigator were central categories of trustworthiness. Comprehensive study outlines, detailed information on the disease being studied, and sharing of study results improved participants’ willingness to be involved in studies. Participants also value researchers who are scientifically and culturally competent, knowledgeable, attentive and who engage in education and sharing comprehensive resources on diseases impacting vulnerable populations. Conclusions These findings suggest that trustworthy features of the study design and researcher characteristics can provide a foothold to build trust with a population whose mistrust of research is well-documented. Further research on trustworthiness is necessary to develop tools to create a framework for building a trustworthy research environment.

Higher plasma p -tau217 levels have been related to cognitive decline in predominantly European American and European adult samples. Some studies suggest cardiovascular disease (CVD) and kidney disease, comorbidities more common in African American (AA) adults, are associated with cognitive dysfunction and elevated p -tau217; consequently, these comorbidities may confound associations between p -tau217 and cognition. Using p -tau217 thresholds for amyloid (A) and tau (T) positive status, we examined if AT status associated with cognitive decline in an AA sample and if significant associations persisted when adjusting for comorbidities also identified as significant predictors of worsening cognition. N  = 199 African Americans Fighting Alzheimer's in Midlife (AA-FAIM) study participants, without baseline dementia, had cognitive data and plasma (EDTA) p -tau217 (AlzPath, Inc.) for analysis (Table 1). N  = 130 had baseline estimated-glomerular-filtration-rate (eGFR) to assess kidney function. CVD was defined as baseline history of myocardial-infarction, congestive-heart-failure, or stroke. p -tau217 thresholds for amyloid- and tau-positive status (A+>.35pg/mL; T+>.556pg/mL) were derived from previous receiver-operating-characteristic-curve analyses of AA-FAIM amyloid- and tau-PET data. Separate mixed effects models tested whether AT status (A+T+, A+T-, A-T-[reference]), eGFR, 3-level kidney function variable (mild-to-severe, mild, normal[reference]), and CVD moderated relationships between age and decline in: Rey-auditory-verbal-learning-test (RAVLT: immediate- and delayed-recall), log-transformed Trails A and B, semantic fluency, and preclinical-Alzheimer's-cognitive-composite. If AT status, CVD and/or kidney-function were significantly related to same cognitive outcome, the association between AT status and cognition was re-tested adjusting for the comorbidity and age*comorbidity interaction. See Table 2 for covariates. A+T+ status was related to greater decline in log-transformed Trails B and RAVLT immediate-recall; CVD predicted greater decline in log-transformed Trails B; association between mild-to-severely decreased kidney function and decline in RAVLT immediate-recall was not significant ( p  = .10) (Table 2). AT status and comorbidities were not associated with other cognitive outcomes. A+T+ status was associated with greater declines in log-transformed Trails B and RAVLT immediate-recall when adjusting, respectively, CVD and impaired kidney function and their interactions with age (Table 2; Figure 1). In AA-FAIM, plasma p -tau217 A+T+ status was related to greater decline in executive function and immediate-recall, even following comorbidity adjustment. Replication is needed in samples having larger proportions with medical comorbidities.

Individuals’ attitudes toward research predict recruitment, engagement, and retention. The Research Attitudes Questionnaire (RAQ), developed to predict individuals’ willingness to participate, is often used in AD research. It can be used to identify strategies to mitigate individuals’ reluctance to engage in research. To date, there are mixed findings regarding diverse groups’ willingness to engage in AD research. Between-group comparisons are only meaningful and valid when the measures being used reflect true group differences in the construct i.e., measurement invariance (MI). One of the prerequisites for meaningful comparisons across diverse groups is to have measurement invariance. The study goal was to examine the suitability of the RAQ across age and ethno-racialized identities. We explored the MI of the 7-item RAQ using Confirmatory Factor Analysis (CFA) via Mplus in a community-derived sample of 457 younger and 594 older African American, 307 younger and 339 older American Indian/Alaska Native, and 173 younger and 679 older Non-Hispanic White male and female individuals. CFA evaluated the one-factor model across the groups. Subsequently, loadings, means, and residuals were consecutively constrained to equality. We examined whether the increased restrictions produced significant changes in the data-model fit to determine whether conditions were met to demonstrate varying levels of measurement invariance. Table 1 summarizes sample demographics and provides mean total RAQ scores. The RAQ showed good internal consistency across age and ethno-racialized groups (Cronbach’s a ranging from 0.78 to .85). A one-factor model showed acceptable fit across the groups (Table 2). The results of the cross-sample invariance tests are provided in Table 3. We found evidence of configural invariance; comparisons of successive models supported metric invariance, and scalar invariance. Strict invariance was not supported. These data suggest that across the 6 groups, who differed in terms of age and ethno-racial identity, the strengths of associations between the specific scale items and the latent construct being assessed by the RAQ are the same. However, the groups may differ in the extent to which they are characterized by the latent variable. This finding supports the suitability of the RAQ for cross-cultural comparisons of willingness to engage in research.

Background:The Research Attitudes Questionnaire (RAQ), developed to predict individuals' willingness to participate, is often used in Alzheimer's Disease and related dementia research. Objective:The present investigation aimed to examine the suitability of the RAQ across age groups and three different racialized identities, i.e., to see whether the RAQ showed measurement invariance. Methods:We administered the RAQ to six groups of participants: 457 younger and 594 older African Americans, 207 younger and 339 older American Indian/Alaska Native, and 173 younger and 679 older non-Hispanic White adults. Results:Confirmatory factor analysis indicated that the best-fitting model was one-factor. All six groups fit the model well, with Comparative Fit Indices > 0.95. A series of cross-sample invariance tests using increasing constraints on factor loadings, means, and residuals revealed evidence of configural invariance, metric invariance, and partial scalar invariance. Conclusions:These findings support the suitability of the RAQ for cross-cultural and/or age comparisons of willingness to engage in research in the groups and context studied.

In the United States, 18.6% of Black Americans over age 65 are impacted by Alzheimer's disease and ∼ 5% participate in clinical trials. Research has shown that limited access to education, information and mistrust in the healthcare system contribute to less representation of Black participants in clinical trials. Mistrust in the healthcare system is a well-known barrier to clinical trial participation. To gauge Black Americans’ views on trust, our study used the community based participatory research framework to increase dementia awareness, provide services to Black participants and seek the community's views on trust. We conducted four focus group discussions with Black participants 45 years and older without self-reported cognitive impairment. Discussions were facilitated by a race concordant moderator and a moderator not identifying as Black via a virtual platform. The transcripts were analyzed by one geriatric physician and two qualitative researchers using inductive thematic analysis. Central themes were identified using narrative summaries and mind maps. Our results show a conceptual framework of how participants view trust. Participants self-identified as Black, had a mean age of 63, were predominantly female and completed some college. Our study showed that Black participants developed trust with researchers when they portrayed shared historical experiences, cultural awareness, and had previously established relationships within the community. Participants also valued diverse research teams and researchers with disease expertise. Participants desired to be heard, educated on illnesses affecting their community and informed of comprehensive study results. Data analysis revealed that trust and established relationships with the research team increased participants’ willingness to participate in future studies. See Figure 1 Black participants are willing to participate in research studies, but we as researchers must first create a welcoming aura through partnerships. As we build upon more inclusive research study designs, it will be important for future studies to incorporate relationship building qualities into a standardized inclusive recruitment and retention protocol.

Support for the association between Mild Behavioral Impairment (MBI) and cognitive decline continues to emerge, but mechanisms remain unclear, particularly in racially diverse cohorts. We investigated relationships between MBI, cognition and six different biomarkers among a richly characterized sample of white and African American (AA) middle aged and older adults. AA participants were enrolled in African Americans Fighting Alzheimer's in Midlife (AA-FAIM), an ancillary study of the Wisconsin Disease Research Center's (WADRC) Clinical Core and the Wisconsin Registry for Alzheimer's Prevention (WRAP). Participants enrolled in the WADRC were included in analyses if they were without dementia, had an available Neuropsychiatric Inventory Questionnaire (NPI-Q) from at least two consecutive visits and one of three biomarker modalities: Hippocampal volume derived from MRI ( n  = 312), centiloid concentration derived from [ 11 PiB-C]-PET ( n  = 147) or ptau217 pg/mL, Aβ42/40 ratio, glial fibrillary acidic protein pg/mL (GFAP), and Neurofilimant light pg/mL (Nfl) measured in plasma ( n  = 323). We used mixed effects linear models to test if MBI impacts the association between biomarker and cognitive trajectories (i.e. MBI*Biomarker*Time). Cox proportional hazard models were used to assess associations between age to first global CDR >0 occurrence and baseline MBI, most recent biomarker value, and the interaction between the two. Cognitive outcomes included measures of speed, mental flexibility and memory. There were no significant 3-way interactions between MBI and HPV, ptau217, Aβ42/40, NfL or GFAP. Individuals with MBI exhibited steeper declines in all cognitive outcomes. Multiple significant 2-way associations emerged between p -tau217, NfL and GFAP and cognitive decline. After correcting for multiple comparisons, higher centiloid values significantly associated with steeper declines in memory. Cox proportional hazard models yielded no significant interactions between any biomarkers and MBI. Baseline MBI significantly associated with time to CDR>0 in GFAP and centiloid models, although potential overfitting limits interpretability. Our findings provide preliminary support for the notion that MBI affects the relationship between specific disease biomarkers and cognitive decline, with evidence of this in our centiloid results. Centiloid concentration, a standardized measure of beta amyloid-PET, may represent a particularly sensitive marker of early, stable brain changes associated with MBI in this racially diverse cohort.

Objectives To determine whether MBI associates with worse cognitive performance over time and with incident cognitive decline in an older, racially/ethnically diverse cohort at early stages of cognitive change. Design This observational cohort study followed participants from the Wisconsin Alzheimer’s Disease Research Center Clinical Core (WADRC) for up to 13 visits. Setting An urban university research center. Participants Participants from the WADRC Clinical Core were included in this convenience sample if they were without dementia, had undergone at least 1 cognitive assessment, and completed measures of cognitive, clinical and affective function. Measurements MBI was assessed using the Neuropsychiatric Inventory. Linear mixed effects models (LME) were fit to cognitive outcomes Trailmaking Tests A and B (TMT-A, B) and Wechsler Logical Memory (LM). Cox proportional hazard models assessed whether MBI was related to risk for incident global Clinical Dementia Rating Scale (CDR >0). Results N = 584 participants with mean age 64.6 years, range 46-92.6 years, 59.4% female and 17% African American. LME results indicated participants with MBI exhibited worse age-associated decline on TMT-B, compared to those without MBI (beta=0.008, p = 0.01, CI: 0.002, 0.01, t(337) = 2.4, p = 0.01). MBI at baseline was associated with a significant hazard ratio (HR) indicating an increased risk of decline on the CDR (HR: 2.84; HR 95% CI: 1.68 — 4.81; p = 0.0001). Conclusions MBI associated with worse cognitive performance and incident cognitive decline in a racially diverse, older adult sample at early stages of cognitive change. Increased awareness of the late life emergence of neuropsychiatric symptoms is warranted to assist in identification and improve prognostication and treatment of neurodegenerative disease.

To increase participation of underrepresented groups (URG) into clinical research studies such as the AHEAD study, a study assessing lecanemab in participants with preclinical Alzheimer’s disease (AD), it is necessary to understand and address barriers in an effort to mitigate them. Toward this goal, methods assessing community needs and plans to meet those needs are imperative. Our ultimate goal is to aid URG in understanding the clinical research process and to empower them to participate in AD research so that approved therapies are applicable to them. This work was made possible by an AHEAD Diversity Recruitment Supplement grant funded to University of Wisconsin-Madison (UW-Madison) by the Alzheimer’s Clinical Trial Consortium (ACTC) to increase URG participation in the AHEAD study. Our approaches include using surveys to identify barriers in order to develop a strategic plan to overcome them. Surveys assessed whether potential participants had knowledge of 1) lecanemab, 2) the AHEAD study, and 3) if they would be comfortable in a study involving a medication, among others. Interested individuals were rewarded with a swag bag for completing the surveys The findings showed that URG were not likely to be aware of lecanemab or the AHEAD study. Additionally, while they wanted to know if they met the criteria for the study, they were less comfortable about a clinical study involving a medicine (Figures 1). Moreover, we identified other barriers to research participation, such as factors that were more likely to prevent URG from meeting study criteria. These included not knowing family history or their AD biomarker status, which was necessary inclusion criteria for individuals age 55-64 (Figure 2). Surveys at community events are useful in identifying barriers to the engagement of URG in AD clinical trials. To decrease barriers and push the pendulum towards increased participation of URG in biomedical research, increased educational efforts are needed on AD, the clinical trial process, and drug development. Moreover, researchers must make sure that URG are not ruled out from the study onset, meaning inclusion criteria must consider some unknown challenges such as not knowing medical or family history.

Background: Past research suggests that ethnoracialized groups differ in their willingness to engage in preclinical Alzheimer's disease (AD) research overall. Studies indicated that participation willingness was affected by attitudes toward research and perceived invasiveness of biomarker collection techniques. However, comparative quantitative studies are few, and minoritized groups are under-included. Objective: In a cross-sectional online survey, we sought to explore community-based adults' willingness to engage in preclinical AD biomarker testing, comparing their attitudes about research and different types of biomarker procedures. Methods: We conducted an online survey with a diverse group of participants. African American (AA), American Indian/Alaska Native (AI/AN), Latinx (LTX), and Non-Hispanic White (NHW) adults aged 26-90 were asked about their research attitudes, biomarkers, and willingness to participate in specific biomarker test procedures (i.e., brain imaging via PET scanning, blood draws, and cerebrospinal fluid collection by lumbar puncture). We also assessed participants' perceived safety, burden, and distress for each of the three biomarker collection methods. To understand the association between research willingness and ethnoracial identity, we ran linear regression models for each procedure, adjusting for age, gender, educational attainment, and attitudes toward research. Results: The AA group expressed greater willingness to engage in biomarker testing involving blood draws than the NHW group. The AI/AN group was significantly less willing to undergo lumbar puncture than the NHW group; this difference remained after adjusting for various sociodemographic factors and research attitudes. Conclusions: Respondents' willingness to engage in preclinical AD biomarker research was affected by their perceptions about the testing collection procedure.

INTRODUCTION:Medical conditions prevalent in Black adults within the United States have been associated with plasma tau phosphorylated at threonine 217 (p-tau217); however, insufficient p-tau217 research has been conducted with Black adults. METHODS:Participants included n = 233 predominantly cognitively unimpaired adults enrolled in the African Americans Fighting Alzheimer's in Midlife study. Subsamples had creatinine (n = 137) and positron emission tomography (PET; amyloid-PET = 65 [amyloid-PET-positive = 16/65]; tau-PET = 70). We tested whether p-tau217 (ALZPath, Inc.) varied by medical condition and amyloid- and tau-PET-positivity status and assessed the diagnostic accuracy of p-tau217. RESULTS:Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, cardiovascular disease (CVD), and amyloid- and tau-PET-positive status demonstrated higher p-tau217. Effect sizes (rpb): eGFR <60 group = 0.48, CVD = 0.25, amyloid-PET-positive status = 0.54; tau-PET-positive status = 0.56. Lower eGFR was related to higher p-tau217 when adjusting for amyloid-PET. For abnormal amyloid-PET and tau-PET, p-tau217 exhibited areas under the curve of 0.90 and 0.89, respectively. DISCUSSION:Plasma p-tau217 showed promise as an Alzheimer's biomarker in Black adults; however, kidney function and CVD should be considered when interpreting levels. HIGHLIGHTS:Plasma tau phosphorylated at threonine 217 (p-tau217) was tested in a sample of Black middle-aged and older adults. Level of p-tau217 was higher in impaired kidney function and cardiovascular disease. Obesity and diabetes were not related to p-tau217. Level of p-tau217 was higher in amyloid- and tau-PET-positive status. Plasma p-tau217 showed good receiver-operating characteristic area under the curve for abnormal amyloid- and tau-PET.

Support for the association between Mild Behavioral Impairment (MBI) and cognitive decline continues to emerge, but mechanisms remain unclear, particularly in racially diverse cohorts. We investigated relationships between MBI, cognition and six different biomarkers among a richly characterized sample of white and African American (AA) middle aged and older adults. AA participants were enrolled in African Americans Fighting Alzheimer's in Midlife (AA-FAIM), an ancillary study of the Wisconsin Disease Research Center's (WADRC) Clinical Core and the Wisconsin Registry for Alzheimer's Prevention (WRAP). Participants enrolled in the WADRC were included in analyses if they were without dementia, had an available Neuropsychiatric Inventory Questionnaire (NPI-Q) from at least two consecutive visits and one of three biomarker modalities: Hippocampal volume derived from MRI ( n  = 312), centiloid concentration derived from [ 11 PiB-C]-PET ( n  = 147) or ptau217 pg/mL, Aβ42/40 ratio, glial fibrillary acidic protein pg/mL (GFAP), and Neurofilimant light pg/mL (Nfl) measured in plasma ( n  = 323). We used mixed effects linear models to test if MBI impacts the association between biomarker and cognitive trajectories (i.e. MBI*Biomarker*Time). Cox proportional hazard models were used to assess associations between age to first global CDR >0 occurrence and baseline MBI, most recent biomarker value, and the interaction between the two. Cognitive outcomes included measures of speed, mental flexibility and memory. There were no significant 3-way interactions between MBI and HPV, ptau217, Aβ42/40, NfL or GFAP. Individuals with MBI exhibited steeper declines in all cognitive outcomes. Multiple significant 2-way associations emerged between p -tau217, NfL and GFAP and cognitive decline. After correcting for multiple comparisons, higher centiloid values significantly associated with steeper declines in memory. Cox proportional hazard models yielded no significant interactions between any biomarkers and MBI. Baseline MBI significantly associated with time to CDR>0 in GFAP and centiloid models, although potential overfitting limits interpretability. Our findings provide preliminary support for the notion that MBI affects the relationship between specific disease biomarkers and cognitive decline, with evidence of this in our centiloid results. Centiloid concentration, a standardized measure of beta amyloid-PET, may represent a particularly sensitive marker of early, stable brain changes associated with MBI in this racially diverse cohort.

BACKGROUND:Mild behavioral impairment (MBI) is associated with all-cause dementia. Little is known about MBI's effects on cognitive function among individuals in earlier disease stages, particularly in racially diverse samples. We examined relationships between MBI and cognitive decline in a richly characterized sample of white and African American (AA) older-middle aged adults. AA participants were enrolled in African Americans Fighting Alzheimer's in Midlife (AA-FAIM), an ancillary study of the Wisconsin Disease Research Center's (WADRC) Clinical Core. METHOD:Analytic sample included participants without dementia, with ≥1 study visits and measures of cognitive/clinical function. A baseline MBI rating (present/absent) was derived using study partners' report of neuropsychiatric symptoms at two consecutive visits, (i.e., two consecutive positive MBI scores = MBI present). Cognitive outcomes included measures of speed, mental flexibility and memory. RESULT:Table 1 provides characteristics by MBI status for white (N = 450), AA (N = 100), and other underrepresented group (URG) (N = 34) participants. In the full sample, baseline MBI significantly moderated cognitive trajectory on Trails B, though not on any other tasks. Participants with MBI displayed worse trajectory of decline on Trails B relative to those without MBI (Figure 1). Additionally, MBI at baseline significantly predicted progression to cognitive impairment CDR >0 (HR est: 2.84; HR 95% CI: 1.68 - 4.81; p = 0.0001) (Figure 2). Stratified analysis in a smaller AA subgroup showed a similar pattern but was not significant. CONCLUSION:MBI associated with more adverse cognitive trajectory and predicted incident cognitive decline in older, middle aged participants without dementia. Our findings highlight the importance of identifying MBI as a possible target for intervention in early disease stages. A fifth of our sample (21.5%) identified as Black/URG. Still, ongoing work in inclusive cohorts is needed to better understand MBI in under-represented groups.

BackgroundDespite the disproportionate impact of Alzheimer’s disease (AD) dementia on Black/African-American and American Indian/Alaska Native groups, they have been underrepresented in biomarker research. Research investigating underrepresented groups’ willingness to engage in research has primarily relied on qualitative research and/or specialized samples (e.g., patients’ first-degree relatives). Similarly, extant quantitative studies include disproportionately small numbers of these participants. This investigation aimed to understand preclinical biomarker and genetic AD research participation in underrepresented groups to facilitate greater diversity in future biomarker research and clinical trials.MethodWe administered an online questionnaire to 599 Black/African-American, 120 American Indian/Alaska Native, and 725 NonHispanic White adults and assessed demographic characteristics and participants’ views on dementia, research, and genetic and preclinical biomarker testing. Attitudes toward research were examined using the standardized 7-item Research Attitudes Questionnaire (RAQ) measure. Using structural equation modeling, we tested a priori hypotheses regarding willingness to engage in AD preclinical biomarker testing. The specific survey item used as the outcome measure asked for agreement with the statement: “I would be willing to undergo any type of testing necessary if it was the only way to find out if I was at risk for AD before there were any symptoms,” answered on a Likert scale (1=strongly disagree – 7=strongly agree).ResultsThe three groups differed significantly in their attitudes toward research, as measured by total RAQ scores. Despite no differences in opinion regarding the overall usefulness of biomarkers, the ethnoracial groups differed in their willingness to engage in preclinical biomarker testing for dementia. Path analysis revealed an excellent model fit, indicating that attitudes toward research, as measured by the RAQ, influenced biomarker testing willingness. These findings suggest the need for outreach and engagement programs to occur before attempting research recruitment, particularly with BIPOC populations.

Background Depression among older adults is a pressing public health concern, necessitating accurate assessment tools. The Geriatric Depression Scale (GDS) offers a brief and efficient means of screening depressive symptoms, yet its performance across ethno-racial groups remains understudied. This study aimed to compare the ability of various brief forms of the GDS to detect depressive symptoms and to assess potential ethno-racial differences in symptom endorsement among White, Black/African-American, and American Indian/Alaska Native older adults. Methods Data were obtained from the Wisconsin Alzheimer's Disease Research Center (ADRC) clinical cohort, comprising 555 cognitively healthy individuals at risk for dementia. We used participants' baseline data for this cross-sectional analysis. Depressive symptoms were assessed using multiple brief forms of the GDS, derived from a systematic review and meta-analysis. We examined internal consistency and correlations with global Clinical Dementia Rating (CDR) scores. We conducted Kruskal-Wallis tests and post hoc pairwise comparisons to assess ethno-racial group differences in symptom endorsement. Results Descriptive statistics revealed a predominance of female and White participants, with notable representation from Black and American Indian/Alaska Native groups. All GDS versions demonstrated moderate to high internal consistency. Significant positive correlations were observed between GDS scores and global CDR scores. Ethno-racial group differences in depressive symptom endorsement were evident, with Black participants consistently reporting higher levels of symptoms across most GDS versions. However, American Indian/Alaska Native participants endorsed significantly fewer symptoms than Black participants in one GDS version. Conclusion The study highlights the importance of considering ethno-racial differences in depressive symptomatology when assessing older adults. While the GDS demonstrates overall reliability, variations in symptom endorsement across different ethno-racial groups underscore the need for culturally sensitive assessment tools and interventions. Future research should further explore these group differences and develop tailored approaches to depression screening and treatment in diverse older adult populations.

Data suggest that establishing trust supports willingness to participate in research studies; yet there is a shortage of standardized systematic studies testing the effectiveness of various methods of building trust. The Building Bridges pilot study examined ways of establishing trust in communities of color comparing two different interventions. Using African American community leaders’ input, we conducted a mixed method study to investigate participants’ 1) preferred format for community-based interventions, 2) comfort with discussing dementia with researchers/healthcare providers, and 3) attitudes of trust about research and researchers. African American subjects (age ≥ 45 years) without self-reported cognitive impairment completed research attitudes (RAQ) and trust in medical researcher questionnaires, pre- and post-intervention; individual medication reviews (n = 48) and/or public community talks (n = 49). Quantitatively, we compared pre- and post- intervention outcomes with paired Wilcoxon non-parametric sign rank tests; all qualitative themes were analyzed using Nvivo QSR 12. Participants’ mean age was 64 (SD = 9.9). See Table 1 for demographics. Quantitatively, there was greater change in research attitudes and trust following a medication review intervention compared to experiencing a community talk (Figure 1); e.g., participants expressed “positive views about medical research in general” on questionnaires following medication reviews (p = 0.007). Qualitatively, we found a similar trend during our focus group discussions. Focus group members expressed more comfort with the medication review than the community talk resulting from “positive bedside manners, positive feedback, personal 1-on-1 interactions and race concordance.” Focus group participants noted a willingness to participate in future studies because of trust built from their Building Bridges team interactions. “Commonality, better connection, relatability, affinity and cultural similarities” all influenced trust and willingness to participate in future studies. Factors found to reduce trust included: “negative feedback, stereotypes, predominantly white practitioners in medicine and research, clinician unskillfulness, and not feeling seen as a “whole person” by providers” (Figure 2). Findings continue to support our hypothesis that more personalized community engagement approaches have a greater influence on participants’ research attitudes and build interest in research. Additional studies of person-centered recruitment strategies are essential to understanding how to improve trust and positive research attitudes among communities of color.

The prodrome of cognitive declines and/or dementia may include late-life neuropsychiatric symptoms such as apathy. In primarily non-Hispanic White samples, apathy associates with both cognition and amyloid deposition in cognitively intact patients and those with Alzheimer’s disease (AD). However, little is known about these relationships in African Americans, who are both disproportionately affected by AD and under-represented in AD research. Apathy could reflect higher levels of proteinopathy or occur co-morbidly, exacerbating its deleterious effects. We examined associations between apathy and cognition and their potential moderation by plasma beta amyloid in cognitively healthy African American participants. Study participants enrolled in African Americans Fighting Alzheimer’s In Mid-Life(AA-FAIM, a linked study to the WRAP and Wisconsin ADRC) were included in the analytic sample (N = 166; Table 1) if they had ≥1 cognitive visits, plasma amyloid biomarker data, and apathy ratings by study partners using the Neuropsychiatric Inventory Questionnaire (NPI-Q) or the Apathy Evaluation Scale (AES). Cognitive outcomes included performance on measures of processing speed, mental flexibility and immediate and delayed memory. We used linear mixed models to examine association of baseline apathy with cognitive performance measures at multiple time points, and the moderation of apathy-cognition relationships by plasma Aβ42/40 ratio (C 2 N, USA). Apathy-cognitive outcome pairings were selected based on significant findings from a proof-of-concept linear mixed effects analysis of the full Wisconsin ADRC sample. Results are shown in Table 2. Among AA-FAIM participants, NPI-Q apathy was associated with RAVLT immediate (estimate = -7.7, p = .001) and delayed recall (estimate = -3.2, p = .001). However, AES was unrelated to Trails A or B performance. There were no associations between plasma amyloid or the Aβ42/40*apathy interaction term with any cognitive outcomes. Partner-rated apathy, but not plasma Aβ42/40, was related to cognition in our African American participants, an important finding given limited data available on this population. It will be critical to address apathy and its antecedents to improve the cognitive and affective health of African American older adults. Future research needs to expand cohorts to African American and other diverse populations to investigate disease mechanisms in Alzheimer’s disease and related dementias more inclusively.

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.

To ensure that therapies are applicable for all groups, ethnic/racial diversity in Alzheimer’s disease (AD) clinical trials is an ethical imperative. Toward this goal, we developed a recruitment model founded on 1) building trust by providing accurate and transparent information, and 2) using culturally sensitive approaches to address legitimate concerns. Our ultimate goal is to empower individuals from under-represented groups (URG) to participate in AD research. Our group focuses on recruitment of racialized groups. Using a multistep approach (figure1), we established partnerships and created community advisory boards (CABs) comprised of leaders who effectively advocate for community needs. Research projects are presented to the CABs to determine alignment with community needs. Assessments with community leaders and advisory networks help identify opportunities to fulfill community needs. Recruitment of African Americans (AA) into the AHEAD study, a study assessing the recently approved monoclonal antibody, lecanemab in participants with preclinical AD, began by presenting the project to the Black Leaders of Brain Health (BLBH) CAB. Incorporating their input into our approach, we will structure community talks and events in a culturally appropriate manner in discussions with the larger AA community. Example, we utilized a questionnaire at an event to introduce AA participants in a biomarker study to the AHEAD study (figures 2 & 3). Feedback received from BLBH includes advocating to funders, including the NIH to fund research that reflects inclusivity and diversity. BLBH recommended building URG voices into study design by having a diverse scientific team and hiring community members to collect data. Additionally, rather than excessive compensation, researchers should speak to the study benefits both for the individual’s and the community’s health. Finally, BLBH members emphasized the need to include hopeful messages and advice to improve health, rather than merely pointing out that AA are most likely among racial groups to have the disease. Recruitment models involving trust building and partnerships with groups consisting of community members of URG will be mutually beneficial for both the health researcher and the communities that they serve. This may serve as a means to tip the scale toward increased participation by URG in biomedical research.

Abstract 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 (Aβ)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 Aβ42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aβ42/40. Results IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aβ42/40 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 Aβ42/40 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.