Citations

Abstract INTRODUCTION We compared white matter hyperintensities (WMHs) in early‐onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups in the Longitudinal Early‐Onset Alzheimer's Disease Study. METHODS We investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t ‐tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden. RESULTS EOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group. DISCUSSION EOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD. Highlights This study represents a comprehensive characterization of WMHs in sporadic EOAD. WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD. Greater WMH volumes are associated with worse performance on global cognitive tests. EOAD participants have higher WMH volumes compared with CN and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups across all brain regions.

AbstractIntroductionOne goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early‐onset Alzheimer's disease (EOAD).MethodsCerebrospinal fluid (CSF) concentrations of Aβ1‐40, Aβ1‐42, total tau (tTau), pTau181, VILIP‐1, SNAP‐25, neurogranin (Ng), neurofilament light chain (NfL), and YKL‐40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated.ResultsBiomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP‐25, and Ng in EOAD differed significantly from cognitively normal and early‐onset non‐AD dementia; NfL, YKL‐40, and VILIP‐1 did not. Across groups, all biomarkers except SNAP‐25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP‐25 were correlated with at least one cognitive measure.DiscussionThis study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.

Background: The body Mass Index (BMI) is commonly used in clinical practice to screen for obesity and resulting cardiometabolic conditions. Nonetheless, BMI has limited utility as it cannot differentiate body fat (BF). Hypothesis: We tested the hypothesis that BF content measured by air displacement plethysmography (Bod-Pod®) had a stronger association with prevalent hypertension (HTN), diabetes mellitus (DM) and dyslipidemia (DLP) when compared to BMI. Methods: We performed a community-based cross-sectional study on adults attending an employee wellness center from January 2007-December 2011 who had had a body composition assessment with Bod-Pod®. We excluded subjects with history of myocardial infarction, coronary artery disease, congestive heart failure, stroke at baseline. The prevalence of HTN, DM and DLP was assessed across quartiles of BF% and BMI categories. Their association with BF% and BMI was evaluated using linear regression models that adjusted for age, sex, and white race. Results: We included 3,052 individuals; 68 % were women, and the mean age ± SD was 42.09±12.8, BMI was 27.9±6.2; BF% 31.88±10.69, 892 (29.2%) were obese by BMI. Cardiometabolic conditions were prevalent in 496 (16.2%) with HTN, 378 (12.4%) with DM and 743 (24.4%) with DLP. While the prevalence of DM, HTN and DLP increased across BF% quartiles (all p for linearity>0.01), this was not always the case across BMI categories (p for linearity<0.05 for HTN and DLP, and 0.04 for DM) see Figure A . Elevated BF %, better identified individuals with HTN (AUC 0.766 vs 0.625; p<0.001), DM (AUC 0.643 vs. 0.568; p<0.001), DLP (AUC 0.758 vs. 0.593; p<0.001). Conclusion: BF content is better associated with a higher prevalence of HTN, DM, and DLP. Highlighting the role of body composition assessment in primary prevention. Dyslipidemia.

AbstractIntroductionWe examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early‐onset Alzheimer's disease (EOAD; onset 40‐64 years) at the midway point of data collection for the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS).MethodsBaseline NPS (Neuropsychiatric Inventory – Questionnaire; Geriatric Depression Scale) and psychotropic medication use from 282 participants enrolled in LEADS were compared across diagnostic groups – amyloid‐positive EOAD (n = 212) and amyloid negative early‐onset non‐Alzheimer's disease (EOnonAD; n = 70).ResultsAffective behaviors were the most common NPS in EOAD at similar frequencies to EOnonAD. Tension and impulse control behaviors were more common in EOnonAD. A minority of participants were using psychotropic medications, and use was higher in EOnonAD.DiscussionOverall NPS burden and psychotropic medication use were higher in EOnonAD than EOAD participants. Future research will investigate moderators and etiological drivers of NPS, and NPS differences in EOAD versus late‐onset AD.

AbstractObjectiveThe Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early‐onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data‐collection mid‐point.MethodsData from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid‐positive EOAD [n = 212], and amyloid‐negative early‐onset non‐Alzheimer's disease [EOnonAD; n = 70]).ResultsCognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures.ConclusionsWe present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant.HIGHLIGHTS Findings represent the most comprehensive baseline characterization of sporadic early‐onset Alzheimer's disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

AbstractOBJECTIVEInvestigation of learning slopes in early‐onset dementias has been limited. The current study aimed to highlight the sensitivity of learning slopes to discriminate disease severity in cognitively normal participants and those diagnosed with early‐onset dementia with and without β‐amyloid positivityMETHODData from 310 participants in the Longitudinal Early‐Onset Alzheimer's Disease Study (aged 41 to 65) were used to calculate learning slope metrics. Learning slopes among diagnostic groups were compared, and the relationships of slopes with standard memory measures were determinedRESULTSWorse learning slopes were associated with more severe disease states, even after controlling for demographics, total learning, and cognitive severity. A particular metric—the learning ratio (LR)—outperformed other learning slope calculations across analysesCONCLUSIONSLearning slopes appear to be sensitive to early‐onset dementias, even when controlling for the effect of total learning and cognitive severity. The LR may be the learning measure of choice for such analyses.Highlights Learning is impaired in amyloid‐positive EOAD, beyond cognitive severity scores alone. Amyloid‐positive EOAD participants perform worse on learning slopes than amyloid‐negative participants. Learning ratio appears to be the learning metric of choice for EOAD participants.

Introduction: Lewy body dementia (LBD) is common, yet under-recognized and under-researched. To plan studies with the highest impact, engagement of the community personally affected by these conditions is essential. Methods: A web-based survey of people living with LBD and current and former caregivers of people with LBD queried research priorities through forced ranking and exploration of burden of LBD symptoms. Specific caregiving needs in LBD and perceptions of research participation were also investigated. Results: Between April 7, 2021 and July 1, 2021, 984 responses were recorded. Top research priorities included disease-modifying therapies and improved disease detection and staging. People with LBD were interested in pathophysiology and more bothered by motor symptoms; caregivers were interested in risk factors and symptomatic therapies and more bothered by neuropsychiatric symptoms. Few available LBD treatments and resources were rated as helpful, and many valuable services were never received. Previous participation in LBD research was infrequent, but interest was high. Discussion: People with LBD and caregivers highlighted the need for research across all aspects of LBD, from pathophysiology and disease modification to prognosis, education, symptomatic treatments, and caregiver support. Funders should increase support for all aspects of LBD research to target the many needs identified by individuals and families living with LBD.

Abstract Background: To date, the disparate burden of prostate cancer (CaP) in Black men (BM) is still poorly understood. More disconcerting is the limited access to effective, culturally tailored behavioral interventions to support BM diagnosed with CaP, especially at the point of prostate cancer diagnosis (PPCD). From the PPCD, the transition to CaP survivorship can be mentally and physically trying, especially for those lacking emotional and financial support. It is important to provide psycho-oncology support, address social determinants of health (SDOH) and make emotional support available to ethnically diverse BM at the PPCD. We are addressing the CaP disparities experienced by BM at the PPCD through the Inclusive Cancer Care Research Equity (iCCaRE) for Black Men Consortium. Aim: As part of the iCCaRE for Black men Consortium, the specific aim of our project is to develop a PPCD-based Augmented Reality (AR) intervention program, the iCCaRE PPCD Virtual Robot Assistant (ViRA). The ViRA is based on the established efficacy of six CaP care and survivorship (CaPCaS) video interventions, and will support BM at the PPCD. Methodology: The efficacy of six CaPCaS videos were established through formative research that included 17 BM in Florida. Based on pre- and post-test design, data were collected from participants using a structured survey tailored to each CaPCaS intervention: Prevention, Detection, Diagnosis, Treatment, Survivorship and Advocacy form. Following the efficacy study, the iCCaRE PPCD ViRA was proposed as one of five iCCaRE Science of Survivorship (S.O.S) projects to improve the quality of life of BM. Results: Most of the participants for the efficacy study reported that they were: US-born BM; married; college educated; earn less than $60,000; retired; have health insurance; have annual health examination; have a regular doctor; and were screened within the last year. The CaPCaS videos were found to be efficacious in improving attitude towards CaP screening, beliefs about CaP screening, perceived behavioral control and CaP knowledge. Participants also rated the quality of the videos high and expressed high satisfaction with the videos. We are currently in the development phase of the PPCD iCCaRE ViRA, which is based on behavioral science and health communications model. The ViRA will provide SDOH navigation services, psycho-oncology support and emotional support. The acceptance and usability of the iCCaRE ViRA will be established at urology clinics in Florida as part of the iCCaRE Consortium HEROICA Phase I study. We will test the central hypothesis that improving SDOH factors and CaPCaS-related factors will lead to an improvement in patient reported outcomes. Conclusion: We established the efficacy of the CaPCaS interventions in supporting BM across the CaP care continuum. The iCCaRE ViRA under development will target intervention at the PPCD and deliver a smart and connected personalized AR-enabled intervention system that will positively impact CaP diagnosis experience of BM. Citation Format: Folakemi Odedina, Che Ngufor, Arnold Merriweather, Deidre Pereira, Jennifer Crook, Fathi Parisa, Roxana Dronca, Ernest Kaninjing, Solomon Rotimi, Kimlin Ashing, Manisha Salinas, Sha’Reff Rashad, John McCall, Ebenezer Erefah, Ayinde Yahaya, Wes Sholes. A point of prostate cancer diagnosis (PPCD) Virtual Robot Assistant (ViRA) intervention for newly diagnosed Black men: An iCCaRE consortium for prostate cancer in Black men project [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B028.

Abstract Background: A recent report from the AACR has found that black men (BM) men have prostate cancer (CaP) death rates that are more than 2 times those for men of any other race or ethnicity. Yet, BM are less likely to receive cutting-edge, or even standard of care treatment compared to their white counterparts. Limited access to care, transportation, patient perception and medical mistrust, as well as cost of care are major contributing factors. Meeting patients where they are and offering treatment in or closer to their homes should help reduce psychological distress and increase access to care and treatment compliance. As part of the iCCaRE for Black men Consortium, we propose a PCHC model which leverages Mayo Clinic Advanced Care at Home (ACH) program and provides a package of care to support the administration of cancer therapy and/or supportive care/symptom management to CaP patients in their homes by specialist healthcare professionals. The objectives of our pilot study are to understand patients’ choice of therapy in choosing the place of treatment and to evaluate the feasibility and impact of PCHC on clinical outcomes, as well as patient reported-outcomes (PRO) and health related quality of life (HQOL). Methodology: For Aim 1, structured questionnaires are used to assess patient preference for location of therapy, at the infusion center or in the home, as well as perceived difficulties and advantages; follow up qualitative data will be collected through semi-structured interviews to capture patients’ thoughts, feelings, attitudes, and questions towards cancer treatments being administered at home versus in a hospital setting. Aim 2 is an observational study of BM with advanced CaP who are participating in a pragmatic, practice-based randomized clinical trial to track acceptability by and impact of home administration of cancer directed or supportive therapy. Results: For Aim 1, data is used to identify themes regarding perceived advantages and concerns of PCHC and inform our understanding of the proportion of patients who are willing to receive and would benefit from this level of care at home. For Aim 2, the following outcomes are evaluated: (a) time to first ER visit and to first hospitalization; (b) HRQoL and quality-adjusted survival; (c) patient satisfaction and compliance, including home time, adherence with symptom self-reporting and compliance with treatment, level of comfort interacting with the care team by phone or tablet, ability to reach a team member for questions or concerns; (d) cost, including out of pocket cost for patients. Conclusion: Our project will provide data on patient understanding and acceptability of cancer care at home and strategies for overcoming cancer care delivery disparities and barriers of access to care for underserved communities. The expected outcome of our project is that PCHC intervention will positively impact CaP treatment, patients’ access and experience with healthcare by developing a new concept of closer-to home cancer care delivery that will reach more patients in underserved communities. Citation Format: Roxana Dronca, Rohit Rao, Michael Maniaci, Folakemi Odedina, Ernest Kaninjing, Kimlin Ashing, Solomon Rotimi, Manisha Salinas, Sha’Reff Rashad, Arnold Merriweather, John McCall, Ebenezer Erefah, Ayinde Yahaya. Feasibility of patient-centered home care (PCHC) to reduce disparities in Black men (BM) with advanced prostate cancer (CaP): An iCCaRE Consortium for prostate cancer in Black men project [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B046.

Abstract Background: Sub-Saharan African immigrants (SSAI) in the United States (US) constitute one of the fastest-growing segments of the immigrant population. Between 2010 and 2018, the SSAI population in the US increased by 53%, significantly outpacing the 12% growth rate for the overall foreign-born population in the US during that time frame. For the purposes of this study, we define SSAI as the 2 million individuals living in the US originally from the region of the African continent located south of the Saharan desert. Despite their growing numbers, little is published about the extent to which SSAI adapt to health behaviors more common in the US or remain immersed in the values, beliefs and practices reflective of their country of origin. Importantly, no study has comprehensively examined the social determinants of health factors among this population and its influence on health-seeking behaviors and decision-making regarding prostate cancer care and treatment options. This study employs the social determinant of migrant health framework to examine the impact of immigration on the health-seeking behaviors of SSAI including informed-decision making, psychosocial effects and coping mechanisms. This study will fill the void of research studies that link social determinant of health and immigration among SSAI. Methods: Grounded theory will guide the study design that include in-depth interviews to document the experiences of SSAI relative to health seeking behaviors, care, and treatment. We explore differences and similarities among participants based on country or region of origin in Africa. We employ the social determinants of migrant health framework to better understand the needs of SSAI prostate cancer survivors in the United States and how to effectively support these survivors. Results: We will present findings based on preliminary interviews conducted with SSAI prostate cancer survivors recruited from Florida or Minnesota. Additionally, we will report on the development of a SSAI social determinant of migration model that explains individual and structural factors that impact the health-seeking behaviors and coping mechanisms among this population. We will provide new understanding about specific social determinant of health factors that can be addressed in intervention studies among SSAI in the United States. Conclusion: This study examines the full range of racial, social, environmental, behavioral and structural factors that SSAI prostate cancer survivors experience. It will illuminate the decision-making process and overall quality of care among this understudied population. Citation Format: Ernie Kaninjing, Gladys Asiedu, Mary Ellen Young, Ebenezer Erefah, Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Solomon Rotimi, Che Ngufor, Arnold Merriweather, Jennifer Crook, Manisha Salinas, Parisa Fathi, Sha’Reff Rashad, John McCall, Ayinde Yahaya. The iCCARE consortium for prostate cancer in Black men: Grounded theory study of the social determinant of health factors among African immigrant men diagnosed with prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B050.