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The recruitment of a parallel, healthy participants (HPs) arm in renal and hepatic impairment (RI and HI) studies is a common strategy to assess differences in pharmacokinetics. Limitations in this approach include the underpowered estimate of exposure differences and the use of the drug in a population for which there is no benefit. Recently, a method was published by Purohit et. al. (2023) that leveraged prior population pharmacokinetic (PopPK) modeling-based simulation to infer the distribution of exposure ratios between the RI/HI arms and HPs. The approach was successful, but it was a single example with a robust model having several iterations of development and fitting to extensive HP data. To test in more studies and models at different stages of development, our catalogue of RI/HI studies was searched, and those with suitable properties and from programs with available models were analyzed with the simulation approach. There were 9 studies included in the analysis. Most studies were associated with models that would have been available at the time (ATT) of the study, and all had a current, final model. For 3 studies, the HP PK was not predicted well by the ATT (2) or final (1) models. In comparison to conventional analysis of variance (ANOVA), the simulation approach provided similar point estimates and confidence intervals of exposure ratios. This PopPK based approach can be considered as a method of choice in situations where the simulation of HP data would not be an extrapolation, and when no other complicating factors are present. [ABSTRACT FROM AUTHOR]

In silico trials are a promising way to increase the efficiency of the development, and the time to market of cardiovascular implantable devices. The development of transcatheter aortic valve implantation (TAVI) devices, could benefit from in silico trials to overcome frequently occurring complications such as paravalvular leakage and conduction problems. To be able to perform in silico TAVI trials virtual cohorts of TAVI patients are required. In a virtual cohort, individual patients are represented by computer models that usually require patient‐specific aortic valve geometries. This study aimed to develop a virtual cohort generator that generates anatomically plausible, synthetic aortic valve stenosis geometries for in silico TAVI trials and allows for the selection of specific anatomical features that influence the occurrence of complications. To build the generator, a combination of non‐parametrical statistical shape modeling and sampling from a copula distribution was used. The developed virtual cohort generator successfully generated synthetic aortic valve stenosis geometries that are comparable with a real cohort, and therefore, are considered as being anatomically plausible. Furthermore, we were able to select specific anatomical features with a sensitivity of around 90%. The virtual cohort generator has the potential to be used by TAVI manufacturers to test their devices. Future work will involve including calcifications to the synthetic geometries, and applying high‐fidelity fluid–structure‐interaction models to perform in silico trials. [ABSTRACT FROM AUTHOR]

BackgroundImmune system conditions of the patient is a key factor in COVID-19 infection survival. A growing number of studies have focused on immunological determinants to develop better biomarkers for therapies.AimStudies of the insurgence of immunity is at the core of both SARS-CoV-2 vaccine development and therapies. This paper attempts to describe the insurgence (and the span) of immunity in COVID-19 at the population level by developing an in-silico model. We simulate the immune response to SARS-CoV-2 and analyze the impact of infecting viral load, affinity to the ACE2 receptor, and age in an artificially infected population on the course of the disease.MethodsWe use a stochastic agent-based immune simulation platform to construct a virtual cohort of infected individuals with age-dependent varying degrees of immune competence. We use a parameter set to reproduce known inter-patient variability and general epidemiological statistics.ResultsBy assuming the viremia at day 30 of the infection to be the proxy for lethality, we reproduce in-silico several clinical observations and identify critical factors in the statistical evolution of the infection. In particular, we evidence the importance of the humoral response over the cytotoxic response and find that the antibody titers measured after day 25 from the infection are a prognostic factor for determining the clinical outcome of the infection. Our modeling framework uses COVID-19 infection to demonstrate the actionable effectiveness of modeling the immune response at individual and population levels. The model developed can explain and interpret observed patterns of infection and makes verifiable temporal predictions. Within the limitations imposed by the simulated environment, this work proposes quantitatively that the great variability observed in the patient outcomes in real life can be the mere result of subtle variability in the infecting viral load and immune competence in the population. In this work, we exemplify how computational modeling of immune response provides an important view to discuss hypothesis and design new experiments, in particular paving the way to further investigations about the duration of vaccine-elicited immunity especially in the view of the blundering effect of immunosenescence.

The combination of machine learning methods together with computational modeling and simulation of the cardiovascular system brings the possibility of obtaining very valuable information about new therapies or clinical devices through in-silico experiments. However, the application of machine learning methods demands access to large cohorts of patients. As an alternative to medical data acquisition and processing, which often requires some degree of manual intervention, the generation of virtual cohorts made of synthetic patients can be automated. However, the generation of a synthetic sample can still be computationally demanding to guarantee that it is clinically meaningful and that it reflects enough inter-patient variability. This paper addresses the problem of generating virtual patient cohorts of thoracic aorta geometries that can be used for in-silico trials. In particular, we focus on the problem of generating a cohort of patients that meet a particular clinical criterion, regardless the access to a reference sample of that phenotype. We formalize the problem of clinically-driven sampling and assess several sampling strategies with two goals, sampling efficiency, i.e., that the generated individuals actually belong to the target population, and that the statistical properties of the cohort can be controlled. Our results show that generative adversarial networks can produce reliable, clinically-driven cohorts of thoracic aortas with good efficiency. Moreover, non-linear predictors can serve as an efficient alternative to the sometimes expensive evaluation of anatomical or functional parameters of the organ of interest.

Background: Immune system conditions of the patient is a key factor in COVID-19 infection survival. A growing number of studies have focused on immunological determinants to develop better biomarkers for therapies. Aim: Studies of the insurgence of immunity is at the core of both SARS-CoV-2 vaccine development and therapies. This paper attempts to describe the insurgence (and the span) of immunity in COVID-19 at the population level by developing an in-silico model. We simulate the immune response to SARS-CoV-2 and analyze the impact of infecting viral load, affinity to the ACE2 receptor, and age in an artificially infected population on the course of the disease. Methods: We use a stochastic agent-based immune simulation platform to construct a virtual cohort of infected individuals with age-dependent varying degrees of immune competence. We use a parameter set to reproduce known inter-patient variability and general epidemiological statistics. Results: By assuming the viremia at day 30 of the infection to be the proxy for lethality, we reproduce in-silico several clinical observations and identify critical factors in the statistical evolution of the infection. In particular, we evidence the importance of the humoral response over the cytotoxic response and find that the antibody titers measured after day 25 from the infection are a prognostic factor for determining the clinical outcome of the infection. Our modeling framework uses COVID-19 infection to demonstrate the actionable effectiveness of modeling the immune response at individual and population levels. The model developed can explain and interpret observed patterns of infection and makes verifiable temporal predictions. Within the limitations imposed by the simulated environment, this work proposes quantitatively that the great variability observed in the patient outcomes in real life can be the mere result of subtle variability in the infecting viral load and immune competence in the population. In this work, we exemplify how computational modeling of immune response provides an important view to discuss hypothesis and design new experiments, in particular paving the way to further investigations about the duration of vaccine-elicited immunity especially in the view of the blundering effect of immunosenescence. [ABSTRACT FROM AUTHOR]

The combination of machine learning methods together with computational modeling and simulation of the cardiovascular system brings the possibility of obtaining very valuable information about new therapies or clinical devices through in-silico experiments. However, the application of machine learning methods demands access to large cohorts of patients. As an alternative to medical data acquisition and processing, which often requires some degree of manual intervention, the generation of virtual cohorts made of synthetic patients can be automated. However, the generation of a synthetic sample can still be computationally demanding to guarantee that it is clinically meaningful and that it reflects enough inter-patient variability. This paper addresses the problem of generating virtual patient cohorts of thoracic aorta geometries that can be used for in-silico trials. In particular, we focus on the problem of generating a cohort of patients that meet a particular clinical criterion, regardless the access to a reference sample of that phenotype. We formalize the problem of clinically-driven sampling and assess several sampling strategies with two goals, sampling efficiency, i.e., that the generated individuals actually belong to the target population, and that the statistical properties of the cohort can be controlled. Our results show that generative adversarial networks can produce reliable, clinically-driven cohorts of thoracic aortas with good efficiency. Moreover, non-linear predictors can serve as an efficient alternative to the sometimes expensive evaluation of anatomical or functional parameters of the organ of interest. [ABSTRACT FROM AUTHOR]

When attempting to answer questions of interest, scientists often encounter hurdles that may stem from limited access to existing adequate datasets as a consequence of poor data sharing practices, constraining administrative practices. Further, when attempting to integrate data, differences in existing datasets also impose challenges that limit opportunities for data integration. As a result, the pace of scientific advancements is suboptimal. Synthetic data and virtual cohorts generated using innovative computational techniques represent an opportunity to overcome some of these limitations and consequently, to advance scientific developments. In this paper, we demonstrate the use of virtual cohorts techniques to generate a synthetic dataset that mirrors a deeply phenotyped sample of preclinical dementia research participants.

Background: Electronic health record (EHR)-based computable phenotype algorithms allow researchers to efficiently identify a large virtual cohort of Human Immunodeficiency Virus (HIV) patients. Built upon existing algorithms, we refined, improved, and validated an HIV phenotype algorithm using data from the OneFlorida Data Trust, a repository of linked claims data and EHRs from its clinical partners, which provide care to over 15 million patients across all 67 counties in Florida.Methods: Our computable phenotype examined information from multiple EHR domains, including clinical encounters with diagnoses, prescription medications, and laboratory tests. To identify an HIV case, the algorithm requires the patient to have at least one diagnostic code for HIV and meet one of the following criteria: have 1+ positive HIV laboratory, have been prescribed with HIV medications, or have 3+ visits with HIV diagnostic codes. The computable phenotype was validated against a subset of clinical notes.Results: Among the 15+ million patients from OneFlorida, we identified 61,313 patients with confirmed HIV diagnosis. Among them, 8.05% met all four inclusion criteria, 69.7% met the 3+ HIV encounters criteria in addition to having HIV diagnostic code, and 8.1% met all criteria except for having positive laboratories. Our algorithm achieved higher sensitivity (98.9%) and comparable specificity (97.6%) relative to existing algorithms (77-83% sensitivity, 86-100% specificity). The mean age of the sample was 42.7 years, 58% male, and about half were Black African American. Patients' average follow-up period (the time between the first and last encounter in the EHRs) was approximately 4.6 years. The median number of all encounters and HIV-related encounters were 79 and 21, respectively.Conclusion: By leveraging EHR data from multiple clinical partners and domains, with a considerably diverse population, our algorithm allows more flexible criteria for identifying patients with incomplete laboratory test results and medication prescribing history compared with prior studies. [ABSTRACT FROM AUTHOR]

Catheter ablation therapy for persistent atrial fibrillation (AF) typically includes pulmonary vein isolation (PVI) and may include additional ablation lesions that target patient-specific anatomical, electrical, or structural features. Clinical centers employ different ablation strategies, which use imaging data together with electroanatomic mapping data, depending on data availability. The aim of this study was to compare ablation techniques across a virtual cohort of AF patients. We constructed 20 paroxysmal and 30 persistent AF patient-specific left atrial (LA) bilayer models incorporating fibrotic remodeling from late-gadolinium enhancement (LGE) MRI scans. AF was simulated and post-processed using phase mapping to determine electrical driver locations over 15 s. Six different ablation approaches were tested: (i) PVI alone, modeled as wide-area encirclement of the pulmonary veins; PVI together with: (ii) roof and inferior lines to model posterior wall box isolation; (iii) isolating the largest fibrotic area (identified by LGE-MRI); (iv) isolating all fibrotic areas; (v) isolating the largest driver hotspot region [identified as high simulated phase singularity (PS) density]; and (vi) isolating all driver hotspot regions. Ablation efficacy was assessed to predict optimal ablation therapies for individual patients. We subsequently trained a random forest classifier to predict ablation response using (a) imaging metrics alone, (b) imaging and electrical metrics, or (c) imaging, electrical, and ablation lesion metrics. The optimal ablation approach resulting in termination, or if not possible atrial tachycardia (AT), varied among the virtual patient cohort: (i) 20% PVI alone, (ii) 6% box ablation, (iii) 2% largest fibrosis area, (iv) 4% all fibrosis areas, (v) 2% largest driver hotspot, and (vi) 46% all driver hotspots. Around 20% of cases remained in AF for all ablation strategies. The addition of patient-specific and ablation pattern specific lesion metrics to the trained random forest classifier improved predictive capability from an accuracy of 0.73 to 0.83. The trained classifier results demonstrate that the surface areas of pre-ablation driver regions and of fibrotic tissue not isolated by the proposed ablation strategy are both important for predicting ablation outcome. Overall, our study demonstrates the need to select the optimal ablation strategy for each patient. It suggests that both patient-specific fibrosis properties and driver locations are important for planning ablation approaches, and the distribution of lesions is important for predicting an acute response.

Catheter ablation therapy for persistent atrial fibrillation (AF) typically includes pulmonary vein isolation (PVI) and may include additional ablation lesions that target patient-specific anatomical, electrical, or structural features. Clinical centers employ different ablation strategies, which use imaging data together with electroanatomic mapping data, depending on data availability. The aim of this study was to compare ablation techniques across a virtual cohort of AF patients. We constructed 20 paroxysmal and 30 persistent AF patient-specific left atrial (LA) bilayer models incorporating fibrotic remodeling from late-gadolinium enhancement (LGE) MRI scans. AF was simulated and post-processed using phase mapping to determine electrical driver locations over 15 s. Six different ablation approaches were tested: (i) PVI alone, modeled as wide-area encirclement of the pulmonary veins; PVI together with: (ii) roof and inferior lines to model posterior wall box isolation; (iii) isolating the largest fibrotic area (identified by LGE-MRI); (iv) isolating all fibrotic areas; (v) isolating the largest driver hotspot region [identified as high simulated phase singularity (PS) density]; and (vi) isolating all driver hotspot regions. Ablation efficacy was assessed to predict optimal ablation therapies for individual patients. We subsequently trained a random forest classifier to predict ablation response using (a) imaging metrics alone, (b) imaging and electrical metrics, or (c) imaging, electrical, and ablation lesion metrics. The optimal ablation approach resulting in termination, or if not possible atrial tachycardia (AT), varied among the virtual patient cohort: (i) 20% PVI alone, (ii) 6% box ablation, (iii) 2% largest fibrosis area, (iv) 4% all fibrosis areas, (v) 2% largest driver hotspot, and (vi) 46% all driver hotspots. Around 20% of cases remained in AF for all ablation strategies. The addition of patient-specific and ablation pattern specific lesion metrics to the trained random forest classifier improved predictive capability from an accuracy of 0.73 to 0.83. The trained classifier results demonstrate that the surface areas of pre-ablation driver regions and of fibrotic tissue not isolated by the proposed ablation strategy are both important for predicting ablation outcome. Overall, our study demonstrates the need to select the optimal ablation strategy for each patient. It suggests that both patient-specific fibrosis properties and driver locations are important for planning ablation approaches, and the distribution of lesions is important for predicting an acute response. [ABSTRACT FROM AUTHOR]

Introduction: In 2017, the Dutch Ministry of Health introduced bundled payments for birth care on a voluntary basis. This is designed to improve value by increased collaboration among midwives, gynecologists and other maternity care providers. Traditionally, these providers are reimbursed via a fee-for-service payment model. The new payment model aims to shift financial and clinical accountability to a new provider-led entity (a so called integrated birth care organization(ibco)) which functions as a general contractor. In that manner, bundled payments incentivize better coordination of care and reduce the incentives for overuse, duplicated services and low-value care. Currently, within seven regions bundled payment contracts are signed and more contracts are expected in 2019. Objective: To give insight in: 1- the performance of ibco’s who implemented the payment reform versus regions who did not (in terms of health outcomes, utilization and spending) in the period prior to the payment reform, 2- the first experiences of implementing bundled payments in the first year after the payment reform. Outline of the workshop (60+20 min) Performance of birth care organizations prior to the payment reform in terms of health outcomes, utilization and spending (presenter: EdV: 20+5 min) First, the national developments specific for the Dutch situation will be outlined. The early adapters differ from the birth care organization who did not implement bundled payments in 2017 in terms of birth care related spending and caesarean section and epidural rates, while no differences in health outcomes were observed. First experiences of bundled payments (presenter HvD (20+5 min)) Similarities and differences in the set-up of the first ibco will be laid out. This includes the development, content and implications of bundled payment contracts and the found ‘safety net clauses’ around tariffs. Importantly, boundaries for non-integrated birth care organisations and the contributions of bundled payment by experience of professionals in the field are highlighted. These insights are drawn from over 55 semi-structured interviews from all disciplines in and associated with birth care. At the end of the workshop, a discussion on international differences, development of quality indicators and implications of research findings will be encouraged. Fitting with the congress themes Building a stronger integrated primary care Defining measures and outcomes that matter to people Creating shared cultures, norms and values across organisations, professionals and people Learnings/take away messages: - An overview of processes leading to implementation of the first bundled payments in Dutch birth care - National database containing medical spending, health outcomes and quality on an individual level as a foundation for a virtual cohort - From data to knowledge, what does a combined database entail - To understand the Dutch bundled payment model for birth care and how this has been implemented - Insight in the key facilitators and barriers for implementing bundled payment for birth care

Background: Many factors impact caregivers' cognitive health and, by extension, their ability to provide care. This study examined the relationship between psychosocial factors and cognitive performance among dementia caregivers and established a virtual cohort of caregivers for future research. Methods: Data on 527 caregivers were collected via a Web-based survey that assessed cognitive performance. Caregiver data were compared to corresponding data from 527 age-, race-, gender-, and education-matched controls from a normative database. Caregiver self-reported sleep, stress, health, and social support were also assessed. Results: Caregivers performed significantly worse than controls on 3 of 5 cognitive subtests. Stress, sleep, perceived support, self-rated health, years of caregiving, race, and gender were significant predictors of cognitive performance. Conclusion: In this sample of dementia caregivers, psychosocial factors interacted in complex ways to impact cognitive performance. Further investigation is needed to better understand how these factors affect cognitive performance among caregivers. This could be accomplished by the establishment of a virtual cohort that facilitates the development of digital tools to support the evaluation and management of caregiver needs in a manner that helps them remain effective in their caregiving roles.

Computational models for cardiac electro-mechanics have been increasingly used to further understand heart function. Small cohort and single patient computational studies provide useful insight into cardiac pathophysiology and response to therapy. However, these smaller studies have limited capability to capture the high level of anatomical variability seen in cardiology patients. Larger cohort studies are, on the other hand, more representative of the study population, but building several patient-specific anatomical meshes can be time-consuming and requires access to larger datasets of imaging data, image processing software to label anatomical structures and tools to create high fidelity anatomical meshes. Limited access to these tools and data might limit advances in this area of research. In this chapter, we present our semi-automatic pipeline to build patient-specific four-chamber heart meshes from CT imaging datasets, including ventricular myofibers and a set of universal ventricular and atrial coordinates. This pipeline was applied to CT images from both heart failure patients and healthy controls to generate cohorts of tetrahedral meshes suitable for electro-mechanics simulations. Both cohorts were made publicly available in order to promote computational studies employing large virtual cohorts., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

One of the impacts of the coronavirus disease 2019 (COVID-19) pandemic has been a push for researchers to better exploit synthetic data and accelerate the design, analysis, and modeling of clinical trials. The unprecedented clinical efforts caused by COVID-19's emergence will certainly boost future robust and innovative approaches of statistical sciences applied to clinical fields. Here, we report the development of SASC, a simple but efficient approach to generate COVID-19-related synthetic clinical data through a web application. SASC takes basic summary statistics for each group of patients and attempts to generate single variables according to internal correlations. To assess the "reliability" of the results, statistical comparisons with Synthea, a known synthetic patient generator tool, and, more importantly, with clinical data of real COVID-19 patients are provided. The source code and web application are available on GitHub, Zenodo, and Mendeley Data., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Introduction: In 2017, the Dutch Ministry of Health introduced bundled payments for birth care on a voluntary basis. This is designed to improve value by increased collaboration among midwives, gynecologists and other maternity care providers. Traditionally, these providers are reimbursed via a fee-for-service payment model. The new payment model aims to shift financial and clinical accountability to a new provider-led entity (a so called integrated birth care organization(ibco)) which functions as a general contractor. In that manner, bundled payments incentivize better coordination of care and reduce the incentives for overuse, duplicated services and low-value care. Currently, within seven regions bundled payment contracts are signed and more contracts are expected in 2019. Objective: To give insight in: 1- the performance of ibco's who implemented the payment reform versus regions who did not (in terms of health outcomes, utilization and spending) in the period prior to the payment reform, 2- the first experiences of implementing bundled payments in the first year after the payment reform. Outline of the workshop (60+20 min) Performance of birth care organizations prior to the payment reform in terms of health outcomes, utilization and spending (presenter: EdV: 20+5 min) First, the national developments specific for the Dutch situation will be outlined. The early adapters differ from the birth care organization who did not implement bundled payments in 2017 in terms of birth care related spending and caesarean section and epidural rates, while no differences in health outcomes were observed. First experiences of bundled payments (presenter HvD (20+5 min)) Similarities and differences in the set-up of the first ibco will be laid out. This includes the development, content and implications of bundled payment contracts and the found 'safety net clauses' around tariffs. Importantly, boundaries for non-integrated birth care organisations and the contributions of bundled payment by experience of professionals in the field are highlighted. These insights are drawn from over 55 semi-structured interviews from all disciplines in and associated with birth care. At the end of the workshop, a discussion on international differences, development of quality indicators and implications of research findings will be encouraged. Fitting with the congress themes Building a stronger integrated primary care Defining measures and outcomes that matter to people Creating shared cultures, norms and values across organisations, professionals and people Learnings/take away messages: - An overview of processes leading to implementation of the first bundled payments in Dutch birth care - National database containing medical spending, health outcomes and quality on an individual level as a foundation for a virtual cohort - From data to knowledge, what does a combined database entail - To understand the Dutch bundled payment model for birth care and how this has been implemented - Insight in the key facilitators and barriers for implementing bundled payment for birth care. [ABSTRACT FROM AUTHOR]

Lead position is an important factor in determining response to Cardiac Resynchronization Therapy (CRT) in dyssynchronous heart failure (HF) patients. Multipoint pacing (MPP) enables pacing from multiple electrodes within the same lead, improving the potential outcome for patients. Virtual quadripolar lead designs were evaluated by simulating pacing from all combinations of 1 and 2 electrodes along the lead in each virtual patient from cohorts of HF (n = 24) and simulated reverse remodelled (RR, n = 20) patients. Electrical synchrony was assessed by the time 90% of the ventricular myocardium is activated (AT090). Optimal 1 and 2 electrode pacing configurations for AT090 were combined to identify the 4-electrode lead design that maximised benefits across all patients. LV pacing in the HF cohort in all possible single and double electrode locations reduced AT090 by 14.48 ± 5.01 ms (11.92 ± 3.51%). The major determinant of reduction in activation time was patient anatomy. Pacing with a single optimal lead design reduced AT090 more in the HF cohort than the RR cohort (12.68 ± 3.29% vs 10.81 ± 2.34%). Pacing with a single combined HF and RR population-optimised lead design achieves electrical resynchronization with near equivalence to personalised lead designs both in HF and RR anatomies. These findings suggest that although lead configurations have to be tailored to each patient, a single optimal lead design is sufficient to obtain near-optimal results across most patients. This study shows the potential of virtual clinical trials as tools to compare existing and explore new lead designs., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

When attempting to answer questions of interest, scientists often encounter hurdles that may stem from limited access to existing adequate datasets as a consequence of poor data sharing practices, constraining administrative practices. Further, when attempting to integrate data, differences in existing datasets also impose challenges that limit opportunities for data integration. As a result, the pace of scientific advancements is suboptimal. Synthetic data and virtual cohorts generated using innovative computational techniques represent an opportunity to overcome some of these limitations and consequently, to advance scientific developments. In this paper, we demonstrate the use of virtual cohorts techniques to generate a synthetic dataset that mirrors a deeply phenotyped sample of preclinical dementia research participants., Competing Interests: OM and ML are employed by the company Syntegra. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Muniz-Terrera, Mendelevitch, Barnes and Lesh.)

Background: Many factors impact caregivers' cognitive health and, by extension, their ability to provide care. This study examined the relationship between psychosocial factors and cognitive performance among dementia caregivers and established a virtual cohort of caregivers for future research., Methods: Data on 527 caregivers were collected via a Web-based survey that assessed cognitive performance. Caregiver data were compared to corresponding data from 527 age-, race-, gender-, and education-matched controls from a normative database. Caregiver self-reported sleep, stress, health, and social support were also assessed., Results: Caregivers performed significantly worse than controls on 3 of 5 cognitive subtests. Stress, sleep, perceived support, self-rated health, years of caregiving, race, and gender were significant predictors of cognitive performance., Conclusion: In this sample of dementia caregivers, psychosocial factors interacted in complex ways to impact cognitive performance. Further investigation is needed to better understand how these factors affect cognitive performance among caregivers. This could be accomplished by the establishment of a virtual cohort that facilitates the development of digital tools to support the evaluation and management of caregiver needs in a manner that helps them remain effective in their caregiving roles.