Harnessing team science in dementia research: Insights from the Alzheimer's disease research group in South Carolina

Potential of low‐field MRI for increasing participation of Filipino Americans and underrepresented populations in Alzheimer's and dementia research

Differences between men and women are common in Alzheimer's disease and related dementias (ADRD) research. What do they mean? To answer this, rigorous measurement is needed. We investigated current methods being used in ADRD research to measure sex/gender. An online survey was sent to 38 federally-funded Alzheimer's Disease Research Centers (ADRCs), which are required to maintain research cohorts, and 38 federally-funded cohort studies on aging and cognition in the U.S. The response rate was 65.8% (n=50). The survey assessed whether studies enrolled men and women and study protocols for all measures of sex and gender. One or more personnel from 25 ADRCs/ADCs and 25 cohort studies completed the survey from October to December 2020. Of the 50 ADRCs/ADCs and cohort studies, all enrolled men and all but two cohort studies enrolled women. The majority indicated no documented definitions of "man" or "woman": 23/25 (92%) ADRCs/ADCs and 20/25 (80%) cohort studies. Of the seven reporting study definitions, sex/gender definitions included the following: male vs. female (n=2), biologic sex (n=1), defined by another data source ("NACC form" n=1), or only noted that sex/gender was self-reported (n=3). sIn 4/5 instances where multiple personnel reported on a ADRC/ADC or cohort study, reports were inconsistent [e.g., "sex" vs "gender" (n=1) or named "sex" vs unlisted (n=3)]. Most studies (20/25 ADRCs/ADCs, 17/25 cohort studies) had only one measure of sex/gender. In total, 52 measures of sex/gender were described: self-report (n=43), direct observation (n=5), obtained from secondary source (n=3), and biologic specimen (n=1). Self-report measures asked participants to report whether they identified as "male or female" or "man or woman." ADRD research efforts in the U.S. appear to consistently enroll men and women. However, there is a need to define these terms in ways that ensure inclusivity, representation, and consistency in data collection. It is essential to expand measures of sex/gender in ADRD research beyond self-report data to social, behavioral, and biologic markers in order to aid discovery of specific pathways that affect ADRD outcomes.

The Neighborhoods Study (TNS) is a novel investigation of adverse social exposome and brain health leveraging 22 Alzheimer's Disease Research Centers (ADRCs). TNS aims to understand if the adverse social exposures increase Alzheimer's disease and related dementias (ADRD) risk. TNS uses innovative methods to determine lifetime addresses of living (n=≈ 3116) and brain bank cohorts (n=≈ 8637). Addresses are linked to time-concordant adverse social exposome using the Area Deprivation Index (ADI) and summarized over time. Brain health measures are provided by the National Alzheimer's Coordinating Center. We highlight a general overview and methodology of TNS. Data collection is ongoing; however, preliminary findings indicate that the adverse social exposome is related to ADRD biomarkers, neuropathology, and cognitive function. TNS is the largest study of adverse social exposome and ADRD, using the ADRC network to build robust scientific consortia. Its findings will inform ADRD interventions, precision medicine, and policy. The Neighborhoods Study (TNS) investigates adverse social exposome and brain health. TNS is a collaboration among 22 Alzheimer's Disease Research Centers. TNS will give insight on environmental and exposomal factors which may be modifiable. Participant lifetime addresses are linked to temporal adverse social exposome metrics. This study's findings will inform precision approaches to mitigate dementia risk.

Among prominent unmet needs of the Alzheimer's disease and related dementia (ADRD) research community is the ability to leverage opportunities to improve the assessments of persons with and at risk for ADRD. This vision can be realized by providing the tools and infrastructure to transform dementia assessment using remote sensing and digital technologies, pervasive computing, and wireless communications, all in concert with high dimensional data analytics. The Collaborative Aging Research using Technology (CART) initiative (carthome.org), a non-proprietary, sharable end-to-end system for capturing and handling diverse kinds of digital data has been developed. The CART technology platform offers the opportunity to bring new assessment methodology and data types to NIA Alzheimer's Disease Research Centers (ADRC) and related centers and transform the clinical research enterprise. Herein we report on progress in capturing digital data across multiple ADRC's. Participants were recruited from affiliated studies at five NIA ADRC's (Digital Technology Core at Oregon Health & Science University, Minority Aging Research Study at Rush University, Cognitive Empowerment Program at Emory University and Georgia Institute of Technology, ALLFTD study at University of California San Francisco, and a pilot study of Mexican Americans at University of Texas Health Science Center at San Antonio). Field technicians at each center installed the CART technology platform in the home of each participant. A total of 195 research participants have been enrolled across the 5 centers and followed for a median of 19 months (range 1-46). A summary of the center cohorts is provided in the table. The flexibility of the platform and its components has allowed it to successfully be adapted for research in each of these studies with diverse cohorts, use cases, and research aims. Attrition due to technology concerns has been very low (0.5%). Digital biomarker and related data can be readily captured across diverse cohorts, research teams, and settings using a common platform. The largely passive, continuous, and objective data generated with this approach promises to improve the opportunity to create more quantitative and ecologically valid measurements for ADRD phenotypes within the ADRD research community and related research settings.

Journal of the American Geriatrics SocietyVolume 43, Issue 8 p. 890-893 Death Certificate Reporting of Dementia and Mortality in an Alzheimer's Disease Research Center Cohort John M. Olichney MD, Corresponding Author John M. Olichney MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, California Neurology Service, Veteran's Affairs Medical Center, San Diego, California.VA Medical Center, Neurology Service(127), 3350 La Jolla Village Dr., San Diego, CA 92161-3064.Search for more papers by this authorC. Richard Hofstetter PhD, C. Richard Hofstetter PhD Neurology Service, Veteran's Affairs Medical Center, San Diego, California.Search for more papers by this authorDouglas Galasko MD, Douglas Galasko MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, California Neurology Service, Veteran's Affairs Medical Center, San Diego, California.Search for more papers by this authorLeon J. Thal MD, Leon J. Thal MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, California Neurology Service, Veteran's Affairs Medical Center, San Diego, California.Search for more papers by this authorRobert Katzman MD, Robert Katzman MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, CaliforniaSearch for more papers by this author John M. Olichney MD, Corresponding Author John M. Olichney MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, California Neurology Service, Veteran's Affairs Medical Center, San Diego, California.VA Medical Center, Neurology Service(127), 3350 La Jolla Village Dr., San Diego, CA 92161-3064.Search for more papers by this authorC. Richard Hofstetter PhD, C. Richard Hofstetter PhD Neurology Service, Veteran's Affairs Medical Center, San Diego, California.Search for more papers by this authorDouglas Galasko MD, Douglas Galasko MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, California Neurology Service, Veteran's Affairs Medical Center, San Diego, California.Search for more papers by this authorLeon J. Thal MD, Leon J. Thal MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, California Neurology Service, Veteran's Affairs Medical Center, San Diego, California.Search for more papers by this authorRobert Katzman MD, Robert Katzman MD Alzheimer's Disease Research Center, San Diego, La Jolla, California Department of Neuro-sciences, University of California, San Diego, La Jolla, CaliforniaSearch for more papers by this author First published: August 1995 https://doi.org/10.1111/j.1532-5415.1995.tb05532.xCitations: 32 Supported by a Geriatric Neurology Fellowship Award from the Dept. of Veteran's Affairs and NIH Grant AGO-5131. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume43, Issue8August 1995Pages 890-893 RelatedInformation

The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap. The ADRCs longitudinally follow ≈ 17,000 participants, ranging from cognitively unimpaired to dementia, arising from Alzheimer's disease (AD) and related dementias (ADRD; e.g., AD, Lewy body disorders, vascular). Motivated by the Alzheimer's Disease Neuroimaging Initiative's (ADNI) impact, the ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) was formed. Leveraging existing ADRC infrastructure, CLARiTI will integrate standardized imaging and plasma collection to characterize mixed pathologies and use community-engaged research methods to ensure that≥ 25% of the sample is from underrepresented populations (e.g., ethnoculturally minoritized, low education). The resulting ADRD profiles, within a more diverse sample, will provide key resources for ADRCs and an unprecedented, more generalizable publicly available imaging-plasma dataset. HIGHLIGHTS: In vivo detection of mixed pathologies is critical for Alzheimer's disease and related dementias research. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address gaps related to mixed pathologies. The ADRC Consortium for Clarity in ADRD Research Through Imaging (CLARiTI) will enhance this national program by adding standardized imaging and plasma collection to existing ADRC infrastructure. This effort will provide key resources for ADRCs and an unprecedented publicly available imaging-plasma-neuropath dataset.

Recent guidance from the National Alzheimer's Coordinating Center (NACC) recommends remuneration for all Alzheimer's disease (AD) research participants. Given AD research recruitment challenges, we assessed the remuneration practices at Alzheimer's Disease Research Centers (ADRCs). We surveyed 37 ADRCs about remuneration for longitudinal research participants. This included type of remuneration (i.e., compensation, reimbursement) and which study procedures are remunerated. We had a 100% response rate. Most ADRCs (32/37) provide some remuneration but amounts and types varied. Most ADRCs reimburse for travel or food (n=29), compensate for some study procedures (n=32), but most do not remunerate study partners (n=12) or offer financial incentives (n=8). Few (n=6) ADRCs pay for all procedures. Two areas for potential change are compensating for annual clinical and cognitive assessments that are compulsory, and for study partners. Evaluation of the impact of remuneration on recruitment and retention is needed, including for underrepresented groups. Recent guidance recommends remuneration for Alzheimer's disease research participants. We surveyed all Alzheimer's Disease Research Centers about their remuneration practices. Most centers provide some form of remuneration to participants but this is variable. Potential areas for change are remuneration for study partners and annual study visits. Evaluating the impact of remuneration on recruitment and retention is needed.

Our understanding of Alzheimer's disease (AD) and related dementias (ADRD) has grown exponentially, thanks to significant investments by the National Institute on Aging (NIA). This article celebrates the 40th anniversary of the NIA's Alzheimer's Disease Research Centers, highlighting the pivotal role of neuropathology as the bedrock for neurodegeneration research. Neuropathology has championed the key principles of proteinopathy, selective vulnerability, and stereotypic spread. Furthermore, neuropathologic studies advanced our understanding of ADRD prevalence, heterogeneity, clinical–pathological correlations, and genetic underpinnings, spurring biomarker development for target engagement and disease monitoring. Disease‐modifying therapies for AD were inspired and informed by neuropathology. The neuropathology community is poised to refine diagnostics, leveraging digital pathology and integrating genetics and pathomics to enhance subtyping for novel precision medicine approaches. Despite some common misconceptions and logistical challenges, neuropathology continues to be a critical component of the ADRD research infrastructure, serving as a key bridge between allied basic and clinical sciences.HighlightsWe celebrate 40 years of NIA‐funded ADRCs and their contributions through neuropathology studies that have significantly advanced our understanding and treatment of ADRD.Neuropathology uncovers principles of neurodegenerative disease: proteinopathy, selective vulnerability, and stereotypic spread, informing diagnostics and therapies.Development of AD biomarkers with reference to neuropathology enhances accuracy in diagnosis and monitoring, paving the way for targeted disease‐modifying therapies.Integration of digital pathology, genetics, and novel tools in neurodegeneration research promises advanced precision medicine approaches and refined diagnostics.Misconceptions and logistical challenges to neuropathological research are addressed to improve understanding and collaboration.

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. Examine association of MetS features and processing speed and executive function across three racial groups. 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. 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. 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 meet increasing investments in research on Alzheimer's disease (AD) and related dementias (ADRD), investigators must efficiently recruit diverse and representative participant samples. To address this challenge, the Vanderbilt Alzheimer's Disease Research Center (ADRC) sought to develop an integrated digital research infrastructure with a web-based platform. In Fall 2021, we partnered with collaborators and developed the Participant Information Tracking and Coordinating Hub (PITCH). PITCH was developed with a novel iterative user-centered design, allowing for continuous platform development and enhancement. With PITCH we evaluate community-based recruitment strategies, monitor participant progression through the study enrollment pipeline, and simultaneously enrich multiple ADRD studies. The PITCH platform has improved ADRC recruitment efficiency and effectiveness in meeting enrollment goals for two ongoing ADRD cohort studies. With PITCH and data-driven recruitment we will centralize all institutional ADRD research recruitment and successfully enroll more representative samples of research participants. Researchers face challenges recruiting diverse samples with limited recruitment budgets. The Vanderbilt ADRC developed a web platform to enhance recruitment and retention. PITCH builds on previous centralized, data-driven research recruitment models. PITCH has expedited recruitment and study timelines and ensured better inclusion of underrepresented groups.

This paper reports on a Conference organized by the Washington University School of Medicine's (WUSM) Knight Alzheimer Disease Research Center (Knight ADRC), entitled "Enhancing Participation by Minoritized Groups in Alzheimer Disease and Related Dementia (ADRD) Research." It builds on recommendations from a 2018 Workshop. Representatives from all 37 federally funded ADRCs described strategies to enhance the recruitment and engagement of participants from historically minoritized groups. St. Louis community members attended and provided input. The Conference was guided by the 2015 National Institute on Aging (NIA) Health Disparities Research Framework, which delineates that "fundamental life-course factors such as race, ethnicity, and socioeconomic status interact with behavioral and biological characteristics to determine health and disease." The multiple ways of engaging participants described at the Conference provide guidance and strategies that can be adapted and utilized across the ADRC network and other research programs nationally to enhance inclusion of minoritized groups in ADRD research. Highlights Increasing representation in Alzheimer disease and related dementias (ADRD) research is a national priority. The National Conference described strategies to diversify participation in AD research. All Alzheimer's Disease Research Centers (ADRCs) were represented. Local community members attended and participated in breakout sessions. Many community-engaged strategies are being used to enhance recruitment and retention. Approaches can be adapted for local needs and utilized by ADRCs.

BackgroundNovel plasma markers are increasingly accepted as indicators of Alzheimer’s disease and related dementia (ADRD) pathophysiology. The extent to which these markers map with clinical symptoms of disease remains unclear. A proposed early clinical symptom of ADRD is subjective cognitive decline (SCD), the experience that cognition has declined despite normal performance on objective assessment. Mapping the association between ADRD plasma biomarker concentrations and SCD will shed light on the links between pathophysiology and symptomology in the earliest stages of disease. This pilot study examines how SCD (self and informant based) associates with plasma p‐tau181, Aβ42, Aβ40 and neurofilament light chain (NfL) concentrations.MethodForty‐four (mean aged=68 years) cognitively unimpaired individuals and 41 informants were recruited from the Columbia University Alzheimer's Disease Research Center. Levels of plasma ADRD biomarkers (Aß42, Aß40, p‐tau181 and NfL) were measured on the Simoa HD‐X platform. SCD was measured with two dichotomous variables indicating whether there had been a decline in memory relative to previous ability reported by the participant and their informant. Eight unadjusted linear regression models examined self and informant SCD as predictors of each plasma marker. Models were then adjusted for relevant covariates, and interactions with age and sex were considered.ResultAs reported in Table 1, unadjusted models showed that self‐reported SCD was associated with higher NfL. Informant‐reported SCD was also associated with higher plasma NfL as well as higher p‐tau181. Effect sizes were reduced after adjustment and only self‐reported SCD remained associated with higher NfL. Male sex was associated with greater levels of NfL in those who had SCD.ConclusionSCD had stronger associations with a marker of neurodegeneration than amyloid or tau burden. Findings are in line with previous studies showing that NfL has a close relationship with clinical impairments such as cognitive decline. Sample size and type of assay utilized in this study could have limited our ability to see associations with tau and amyloid burden. Futures studies should examine how the combination of plasma markers and early clinical symptoms can aid the predictive utility of plasma markers for onset and progression of clinical symptoms.

Developments in Alzheimer's disease blood‐based biomarkers research have provided critical information as to their use in early detection and assessments of progression in patients. The National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) Biomarker Assay Laboratory (BAL) was developed to provide expertise and access to robust and reliable research‐use‐only biomarkers (not for medical decision making) for the Alzheimer's disease and related dementias (ADRD) research community. The NCRAD BAL is a quality‐focused laboratory delivering biomarker data through the use of highly standardized procedures and highly automated instrumentation with the goal of limiting pre‐analytical variability while preparing samples for analysis, including limiting lot‐to‐lot variability of the assays. As biomarkers become United States Food and Drug Administration (FDA) ‐approved and move into use in CLIA labs, the NCRAD BAL will bring forward new platforms and assays reflecting the most current research‐use‐only biomarkers to support the research mandate of the ADRD research community.HighlightsThe National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) has developed a Biomarker Assay Laboratory to support research of robust and reliable fluid biomarkers for Alzheimer's disease and neurodegeneration.NCRAD supports Alzheimer's Disease Research Centers by providing biomarker analyses on samples with clinical and imaging data through the National Institute on Aging (NIA) ‐funded Alzheimer's Disease Center Fluid Biomarker Initiative.The NCRAD Biomarker Assay Laboratory focuses on decreasing variability that will affect study results by utilizing highly standardized and automated procedures, strict monitoring of control measures, and controlling for lot‐to‐lot and instrument‐to‐instrument variability.

The Alzheimer's Disease Research Centers (ADRCs) consortium represents a critical locus of research on Alzheimer's disease and related disorders (ADRD) prevention, diagnosis, and intervention. Through the National Alzheimer's Coordinating Center's (NACC) standardized protocol, the Uniform Data Set (UDS), ADRCs have collected rich, harmonizable clinical and cognitive data. However, the collection of social data has been sparse and Center specific, constraining ADRD science that addresses research priorities on social determinants of health (SDOH) and health equity. Capitalizing on the transition to a revised UDS version 4, an interdisciplinary committee representing 10 ADRCs reviewed the literature and instrumentation, ultimately creating a brief module covering multiple domains and levels of exposure required for mechanistic studies of SDOH and brain health. This article offers rationale, empirical support, and guidance for using the selected constructs: transportation security, financial security, social connectedness, health care experiences, and discrimination, as well as recommendations for next steps that each ADRC can take to maximize local and field-level progress. HIGHLIGHTS: Social determinants of health (SDOH) play a role in Alzheimer's disease and related dementias (ADRD) risk, diagnosis, care, and research participation. A new module adds SDOH to a revised Uniform Data Set (UDS) for the Alzheimer's Disease Research Center (ADRC) consortium. UDS SDOH include transportation, socioeconomic status, social relationships, health care, and discrimination. We provide evidence for causal SDOH associations with ADRD and guidelines for use. We include recommendations for next steps and expanding the impact of the SDOH module.

INTRODUCTIONWe compared and measured alignment between the Health Level Seven (HL7) Fast Healthcare Interoperability Resources (FHIR) standard used by electronic health records (EHRs), the Clinical Data Interchange Standards Consortium (CDISC) standards used by industry, and the Uniform Data Set (UDS) used by the Alzheimer's Disease Research Centers (ADRCs).METHODSThe ADRC UDS, consisting of 5959 data elements across eleven packets, was mapped to FHIR and CDISC standards by two independent mappers, with discrepancies adjudicated by experts.RESULTSForty‐five percent of the 5959 UDS data elements mapped to the FHIR standard, indicating possible electronic obtainment from EHRs. Ninety‐four percent mapped to the CDISC standards, demonstrating high compatibility with industry standards.DISCUSSIONThe study highlights the feasibility of harmonizing ADRC data with industry and clinical standards. CDISC demonstrated superior alignment with ADRC UDS data, whereas FHIR showed potential for improvement through resource maturation and enhanced standardization.HighlightsForty‐five percent of Alzheimer's Disease Research Center Uniform Data Set (ADRC UDS) data elements could be mapped to Fast Healthcare Interoperability Resources (FHIR), indicating potential electronic health records (EHRs) extraction.Ninety‐four percent of ADRC UDS data elements could be mapped to Clinical Data Interchange Standards Consortium (CDISC) Study Data Tabulation Model (SDTM), showing high industry compatibility.Identified areas for improving data standards harmonization in Alzheimer's disease and related dementias (ADRD) research.Systematic mapping method aligns ADRC UDS with Health Level Seven (HL7) FHIR and CDISC SDTM standards.Results support feasibility of data sharing across ADRC research, EHRs, and industry.