key: cord-0708367-l97eif8l authors: O'Bryant, Sid E.; Johnson, Leigh A.; Barber, Robert C.; Braskie, Meredith N.; Christian, Bradley; Hall, James R.; Hazra, Nalini; King, Kevin; Kothapalli, Deydeep; Large, Stephanie; Mason, David; Matsiyevskiy, Elizabeth; McColl, Roderick; Nandy, Rajesh; Palmer, Raymond; Petersen, Melissa; Philips, Nicole; Rissman, Robert A.; Shi, Yonggang; Toga, Arthur W.; Vintimilla, Raul; Vig, Rocky; Zhang, Fan; Yaffe, Kristine title: The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics date: 2021-06-21 journal: Alzheimers Dement (Amst) DOI: 10.1002/dad2.12202 sha: 3a1b0d82fce94c298bc3d92432ef25f6da61fb42 doc_id: 708367 cord_uid: l97eif8l INTRODUCTION: Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature. METHODS: Community‐dwelling Mexican Americans and non‐Hispanic White adults and elders (age 50 and above) were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T magnetic resonance imaging (MRI) of the brain. Amyloid and tau positron emission tomography (PET) scans were added at visit 2. Blood samples were stored in the Biorepository. RESULTS: Data was examined from n = 1705 participants. Significant group differences were found in medical, demographic, and sociocultural factors. Cerebral amyloid and neurodegeneration imaging markers were significantly different between Mexican Americans and non‐Hispanic Whites. DISCUSSION: The current data provide strong support for continued investigations that examine the risk factors for and biomarkers of AD among diverse populations. The percentage of Hispanics 65 and older in the United States will triple by the year 2050. 1 Along with this population growth, when compared to other racial/ethnic groups, Hispanic Americans are expected to experience the largest increase in Alzheimer's disease (AD) and ADrelated dementias (ADRD) by 2060. 2 and AD among Mexican Americans. 4, 5 The extant literature suggests significant differences in MCI and AD among Mexican Americans as compared to non-Hispanic Whites with regard to age at onset, 6 genetic risks, 4,5 medical co-morbidities, 4, 5 and biological profiles. 7, 8, 9 The Health & Aging Brain among Latino Elders (HABLE) study was initiated in September of 2017 under award R01AG054073 with the goals of (1) investigating factors underlying health disparities in MCI and AD among Mexican Americans (eg, younger age at onset) and (2) examining differential pathways to MCI and AD among Mexican Americans (ie, metabolic, inflammatory, depressive) as compared to non-Hispanic Whites. The HABLE study is intended to examine long-term factors associated with incident MCI and AD from mid to late life; therefore, the age for inclusion was set at 50. The 2018 AT(N) framework 10 provided the field with a biological system for studying AD with the explicit goal of advancing novel clinical trials; however, there remains very little research on amyloid (A), tau (T) or neurodegeneration (N) among diverse populations. 11 In fact, the publication itself calls for examination among communitybased, diverse populations. 10 Currently, the sequence, trajectories, timing, and even clinical impact of cerebral amyloid, tau, or neurodegeneration biomarkers among Mexican Americans is unknown. On the other hand, not only do traditional risk factors, proteomic profiles, and apolipoprotein E (APOE) ε4 genotype vary by racial/ethnic group, but data also point to racial/ethnic variability in core AD pathological markers in cerebrospinal fluid (CSF) 12,13,14 and autopsy. 15, 16, 17, 18 In August 2020, the HABLE-AT(N) grant was funded under award number R01AG058533 to examine the hypothesis that the presence, sequence, progression, incidence, and cognitive impact of amyloid, tau, and neurodegenerative biomarkers will be different among Mexican Americans as compared to non-Hispanic Whites. Together grants R01AG054073 and R01AG058533 provide the structure for a largescale multi-ethnic examination of the AT(N) framework. The goal of this article is to provide an overview of the HABLE methods for the field. HABLE data, images, and biofluid samples are now publicly available. 19 The HABLE protocol takes place over multiple appointments com- A custom electronic data capture (EDC) system was generated. The HABLE interview includes, but is not limited to, questions regarding All participants provide an informant who is familiar with the participant to answer questions regarding daily functioning. A standardized assessment is administered for the Clinical Dementia Rating (CDR) 31 scale and the physician's estimate of duration (PED). 32 The cognitive battery includes tests to assess global cognition, attention/executive functioning, memory, language, and premorbid intelligence (see Table 2 ). Also indicated are the tests that overlap with ADNI, SOL/INCA, and LEADS. Based on our recently published methods, 33,34 HABLE normative ranges were calculated stratified by education (0-7 years, 8-12 years, and 13+), primary language (English or Spanish), and age (median split; < = 65 and > = 66), which are used to assign cognitive diagnoses. All HABLE neuroimaging scans are stored, managed, and processed by the University of Southern California (UCS) Laboratory of Neuroimaging (LONI). 35 The HABLE MRI protocol is based on that of ADNI3 using a 3T Siemens Magnetom SKYRA whole-body scanner. The following scans sequences were captured: T1-weighted whole brain vol- Images are reconstructed immediately after the 30-min emission scan. Fasting blood samples are collected and processed per the international guidelines. 37 All assay preparation is completed using a custom Plasma neuronal-derived exosomes (NDEs) are assayed per our previously published protocols. 41 Detailed protocols will be available from the Omics Core. L1CAM-positive NDE cargo proteins will be quantified using Quanterix Simoa assay for Aβ 40 Research cognitive diagnoses were assigned based on self-report and informant report of daily function, expert clinician assignment of CDR scores (using daily function and cognitive information), and neuropsy- As of June 2020, there were a total of n = 1786 participants enrolled in HABLE with data entry and consensus completed on n = 1705, which were included in the current analyses. Due to coronavirus disease 2019 (COVID-19) , recruitment was halted in April 2020. Study procedures began again in July 2020, with Visit 1 assessments ongoing until n = 2000 participants have been enrolled. Demographic characteristics of the cohort (total and split by ethnicity) are presented in Table 3 . The Mexican American cohort was significantly younger (p < 0.001), had fewer years of education (p < 0.001), had a lower annual household income (p < 0.001), and had a higher body mass index (BMI) (p < 0.001) than the non-Hispanic White cohort. The Mexican American cohort was less likely to own their residence (p < 0.001), less likely to have insurance (p < 0.001) and less likely to have a primary care provider (p < 0.001). The Mexican American cohort was more likely to have a consensus diagnosis of hypertension (p = 0.002) and more likely to have a diagnosis of type 2 diabetes (p < 0.001). There was no significant difference in dyslipidemia or depression prevalence. were younger than non-Hispanic White MCI cases (mean age = 71.07, SD = 9.94) (p < 0.001). Raw neuropsychological test scores for the cohort (total and split by ethnicity) are provided in Table 4 . Analysis of covariance (ANCOVA) models were conducted using age, gender, education, and primary MRI: In order to measure "neurodegeneration" from the AT(N) framework (ie, N), the "metaROI" for N was calculated per Jack. 46 In addition, total brain volume and hippocampal thickness were exam- These findings are also important when considering putative factors (risk and/or causal) associated with MCI and AD among Mexican Amer-icans. Mexican Americans were classified as having MCI at significantly younger ages, which is consistent with our prior work. 5 Mexican Americans were more likely to be classified as MCI as compared to non-Hispanic Whites, whereas no differences in dementia prevalence were observed. The HABLE team examined ADNI-criteria for MCI, which resulted in a 30% MCI rate in this cohort, which was considered overpathologizing. Therefore, the more traditional ≤1.5 SD cut-score was implemented. In addition, normative references were created based on prior work 33 ; however, the team has ongoing studies to examine multiple methods for normative consideration that may impact prevalence rates of diagnostic categories across ethnic groups. The current findings demonstrate a link between ethnicity and biological markers thought to be associated with MCI and AD. Mexican Americans had higher levels of glucagon-like peptide-1 (GLP-1), insulin, and glucagon. The same held for glucose and HbA1c (data not shown). Mexican Americans also had significantly higher levels of plasma Aβ40 and total tau. With regards to imaging, Mexican Americans had lower levels of amyloid positivity and significant differences were observed in multiple MRI-based measures of neurodegeneration. By the year 2045 1 the United States will become largely "non-White," with 14% of the U.S. population being African American and 25% being Latino. 1 In addition, by the year 2060, the U.S. population age 65 and older will grow by more among the African American and Hispanic communities as compared to the non-Hispanic White community. 13 African Americans currently have highest the prevalence of AD and ADRD, whereas Hispanics will experience the greatest increase in ADRDs 2 by 2060. Based on these data, the HABLE study (now entitled the Health & Aging Brain Study -Health Disparities, HABS-HD) has expanded to add 1000 African Americans and now includes the three largest racial/ethnic groups in the United States (75% of the population). The overall goal of HABS-HD is to examine the biomarkers of AD within a health disparities framework. 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