AD-related Dementias Research Articles

Suicidal Ideation and Suicide-Attempt-Related Hospitalizations among People with Alzheimer's Disease (AD) and AD-Related Dementias in the United States during 2016-2018.

People living with Alzheimer’s disease (AD) and AD-related dementias (ADRDs) are at a higher risk of suicidal behaviors given intersecting risk factors. Previous studies generally only focused on AD, small clinical samples, or grouped all dementia subtypes together, limiting insights for other ADRD subtypes. The objective of this study was to generate evidence related to the relative burden of suicidal behaviors (suicidal ideation and suicide attempt) among people with AD and ADRDs. This retrospective cross-sectional study identified hospitalizations related to suicidal behaviors (suicidal ideation and suicide attempt) for patients with Alzheimer’s disease (AD) and AD-related dementias using ICD-10-CM codes from the Nationwide Readmissions Database (NRD). A logistic regression model was estimated to assess associations between AD/ADRD subtype and patient characteristics, and the risk for a suicidal-behavior-related hospitalization and modes of harm were reported. During 2016–2018, there were 12,538 hospitalizations related to suicidal behaviors for people with AD/ADRDs. The overall prevalence of suicidal-behavior-related hospitalizations was lowest for AD (0.8%) and highest for frontotemporal dementia (2.6%). Among hospitalizations for suicide attempts, the most common mode of harm was medications or drugs (89.2% of all attempts), followed by weapons (17.7%). We found that there was a difference in the frequency of suicidal-behavior-related hospitalizations among AD/ADRD hospitalized patients across dementia subtypes.

Differential Cognitive Decline in Alzheimer's Disease Is Predicted by Changes in Ventricular Size but Moderated by Apolipoprotein E and Pulse Pressure.

Differential cognitive trajectories in Alzheimer's disease (AD) may be predicted by biomarkers from multiple domains. In a longitudinal sample of AD and AD-related dementias patients (n = 312), we tested whether 1) change in brain morphometry (ventricular enlargement) predicts differential cognitive trajectories, 2) further risk is contributed by genetic (Apolipoprotein E [APOE] ɛ4+) and vascular (pulse pressure [PP]) factors separately, and 3) the genetic + vascular risk moderates this pattern. We applied a dynamic computational approach (parallel process models) to test both concurrent and change-related associations between predictor (ventricular size) and cognition (executive function [EF]/attention). We then tested these associations as stratified by APOE (ɛ4-/ɛ4+), PP (low/high), and APOE+ PP (low/intermediate/high) risk. First, concurrently, higher ventricular size predicted lower EF/attention performance and, longitudinally, increasing ventricular size predicted steeper EF/attention decline. Second, concurrently, higher ventricular size predicted lower EF/attention performance selectively in APOEɛ4+ carriers, and longitudinally, increasing ventricular size predicted steeper EF/attention decline selectively in the low PP group. Third, ventricular size and EF/attention associations were absent in the high APOE+ PP risk group both concurrently and longitudinally. As AD progresses, a threshold effect may be present in which ventricular enlargement in the context of exacerbated APOE+ PP risk does not produce further cognitive decline.

Perceptions of Treatment Burden Among Caregivers of Elders With Diabetes and Co-morbid Alzheimer's Disease and Related Dementias: A Qualitative Study.

Many older adults with diabetes (DM) have co-occurring Alzheimer's Disease (AD) and AD-Related Dementias (ADRD). Complex treatment plans may impose treatment burden for caregivers responsible for day-to-day self-management. The purpose of this qualitative study was to describe caregiver perceptions of treatment burden for people with DM-AD/ADRD. Caregivers (n = 33) of patients with DM-AD/ADRD participated in semi-structured interviews about their caregiver role and perceptions of treatment burden of DM-AD/ADRD management. Qualitative data were analyzed using content analysis (ATLAS.ti). Caregivers reported high levels of burden related to complex treatment/self-management for patients with DM-AD/ADRD that varied day-to-day with the patient's cognitive status. Four themes were: (1) trajectory of treatment burden; (2) navigating multiple healthcare providers/systems of care; (3) caregiver role conflict; and (4) emotional burden. Interventions to reduce caregiver treatment burden should include activating supportive services, education, and care coordination especially, if patient treatment increases in complexity over time.

Dementia patient and caregiver relevant outcomes currently being reported by adult day service centers in the United States.

BackgroundApproximately one third of adults in adult day services (ADS) centers have Alzheimer's disease (AD) and AD‐related dementias (ADRD). Understanding of the impact and effectiveness of ADS on persons living with dementia (PLWD) is limited by a lack of patient and caregiver relevant outcomes (PCRO) data. We identified PCROs collected at ADS sites in states that mandate serial data collection and examined the degree to which these data align with established Dementia Care Practice Recommendations (DCPR) and PCROs used in other areas of long‐term care.MethodsWe conducted an item analysis of regulatory forms used by ADS. Consistent with the methodology used by the Imbedded Pragmatic AD/ADRD Clinical Trials (IMPACT) Collaboratory for PCROs collected in other long‐term care settings, we created a matrix informed by DCPR. We matched each item in regulatory forms reflecting a PCRO to one of the seven DCPR domains as well as to the 53 PCROs from other long‐term care sectors.ResultsTen states routinely collect outcome data in ADS. Among these, 80% assess cognitive function. All 10 states capture PLWD's ability to complete activities of daily living. Presence and frequency of behavioral symptoms were collected by 80% of states. Very few or, in some cases, none of the 10 states, collected PCROs related to care planning and coordination, education, social support, and/or family caregiver burden and support.DiscussionLack of standardized collection of PCROs hampers researchers’ understanding of ADS. The vast majority of PCROs collected center on participants’ physical health; conversely, data on socialization, social support, and caregiver well‐being, which are purportedly the most impactful services offered by ADS centers, are rarely collected. ADS would be well served to focus on these outcome domains as the resulting data could paint a more complete picture of the holistic impact of ADS on PLWD and their caregivers.

Disruption to Transformation: Aging in the New Normal: A Chat With NIA Senior Leadership

The National Institute on Aging (NIA) at the National Institutes of Health, Department of Health and Human Services, is the federally designated lead agency on aging research and supports significant research on aging as a lifelong process. In the last six years, NIA has experienced a tripling of its budget. Although much of this funding is targeted to Alzheimer’s disease (AD) and AD-related dementias research, there has been an increase in funds allocated to non-AD research in keeping with the overall growth of NIH. This symposium will provide a forum for exploration of the implications of the budget increases for the general research community. NIA’s senior staff will discuss research priorities and programs supported by the Institute. A question-and-answer session will follow these remarks on current funding and future priorities and research directions of NIA.

Altered brain functional connectivity and cardiovascular and metabolic risk factors in middle‐aged and older adults

AbstractBackgroundMetabolic and cardiovascular dysfunction accelerates biological aging and increases risk for many diseases, including Alzheimer's disease (AD) and AD‐related dementias (ADRD). The cumulative negative effects that the body and brain sustain due to the exposure to metabolic (e.g., insulin resistance, dyslipidemia), cardiovascular (e.g., blood pressure), and immune (e.g., C‐reactive protein) risk factors (i.e., MCI‐RFs) have been associated with increased vulnerability to cognitive decline later in life. This project examined whether the functional connectivity (FC) measures of core brain networks are altered due to MCI‐RFs, and how such alterations may relate to cognitive functioning.MethodResting fMRI scans were collected in 217 participants (aged 36‐90+ years) of the Human Connectome Project Aging study, and preprocessed using FreeSurfer’s standard stream. Using a seed‐based approach functional maps of the default mode network (DMN), amygdala, and hippocampus seeds were created. The vertex‐wise partial correlation (i.e., FC) measures to the seeds (i.e., correlation between mean seed time series and all other brain voxels’ time series, later transformed onto cortical surface) were computed and used for further group‐level analyses. Connectomes were evaluated in relation to a MCI‐RF index (higher index score corresponds to greater risk) including measures of body mass index, insulin and glucose, lipids, blood pressure, renal function, nutritional parameters and C‐reactive protein. Cognition was assessed using a multi‐domain composite index (CCI) encompassing aspects of general cognition, memory, processing speed, and executive functioning.ResultWith increasing age, all three networks showed reductions in network integrity with loss of both within‐network and between‐network functional connections in regions outside of the task‐positive network hubs. After correcting for age effects, associations between FC and MCI‐RF index were mostly observed in the DMN and amygdala. Increased MCI‐RF was associated with reduced negative connectivity (i.e., loss of between‐network connections) in amygdala map, suggesting less regulated networks. Associations with CCI were observed across all three networks’ FC maps but mostly in the amygdala.ConclusionOur findings suggest that MCI‐RFs impact brain network organization, and that connectivity in the amygdala network might be a key to the interface between metabolic, cardiovascular and immune dysfunction and cognition.

Gender Disparities in Anti-dementia Medication Use among Older Adults: Health Equity Considerations and Management of Alzheimer's Disease and Related Dementias.

Objective: The prevalence of Alzheimer’s disease and related dementias (ADRD) in women is higher than men. However, the knowledge of gender disparity in ADRD treatment is limited. Therefore, this study aimed to determine the gender disparities in the receipt of anti-dementia medications among Medicare beneficiaries with ADRD in the U.S.Methods: We used data from the Medicare Current Beneficiary Survey 2016. Anti-dementia medications included cholinesterase inhibitors (ChEIs; including rivastigmine, donepezil, and galantamine) and N-methyl-D-aspartate (NMDA) receptor antagonists (including memantine). Descriptive analysis and multivariate logistic regression models were implemented to determine the possible gender disparities in the receipt of anti-dementia medications. Subgroup analyses were conducted to identify gender disparities among beneficiaries with Alzheimer’s disease (AD) and those with only AD-related dementias.Results: Descriptive analyses showed there were statistically significant differences in age, marital status, and Charlson comorbidities index (CCI) between Medicare beneficiaries who received and who did not receive anti-dementia medications. After controlling for covariates, we found that female Medicare beneficiaries with ADRD were 1.7 times more likely to receive anti-dementia medications compared to their male counterparts (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.19–2.45). Specifically, among Medicare beneficiaries with AD, females were 1.2 times more likely to receive anti-dementia medications (Odds Radio: 1.20; 95% confidence interval: 0.58–2.47), and among the Medicare beneficiaries with only AD-related dementias, females were 1.9 times more likely to receive anti-dementia medications (OR: 1.90; 95% CI: 1.23–2.95).Conclusion: Healthcare providers should be aware of gender disparities in receiving anti-dementia medications among patients with ADRD, and the need to plan programs of care to support both women and men. Future approaches to finding barriers of prescribing, receiving and, adhering to anti-dementia medications by gender should include differences in longevity, biology, cognition, social roles, and environment.

Long-term exposure to ambient air pollution is associated with neuropathologic change of Alzheimer's Disease at Autopsy

BACKGROUND AND AIM: There is a growing body of evidence linking exposure to air pollution with dementia and Alzheimer’s disease (AD). However, the detailed molecular mechanisms explaining how air pollution exposures may affect the human brain are still largely unknown. Investigating the impact of air pollution on markers of AD neuropathology might provide mechanistic insights. We evaluated associations of long-term exposure to air pollution prior to death with three different measures of AD neuropathology: Braak stage; Consortium to Establish a Registry for AD (CERAD) neuritic plaque score; and combined AD neuropathologic change (ABC score). METHODS: We obtained data on the neuropathology markers from autopsy samples collected after 2008 from the Emory University Goizueta Alzheimer’s Disease Research Center Neuropathology Core Brain Bank (N=145 donors from Metro Atlanta, Georgia, USA). Long-term exposures to PM2.5, CO, and NOx were estimated at the deceased’s last address for a fixed 7-year period (2002-2008) via the Research LINE source model (resolution: 250m). We performed ordinal logistic regression for each marker adjusting for age at death, race, gender, educational attainment, and APOE genotype. RESULTS:The average age at death was 76 years (SD=9.5). The medians of exposure to PM2.5, CO, and NOx were 0.32µg/m3, 157.9ppb, 12.9ppb, respectively. After adjustment, one unit increase in 7-year average PM2.5 was associated with higher Braak stage [OR = 5.40 (1.30, 28.25)]. Associations with CERAD [0.83 (0.12, 5.61)] and ABC [2.41 (0.42, 13.95)] scores were not significant and no significant associations were found for CO and NOx (Braak stage: 1.00 (0.99, 1.01) and 1.04 (0.99, 1.10), respectively). CONCLUSIONS:PM2.5 was associated with neuropathologic changes assessed by Braak stage, which characterizes the abundance of neurofibrillary tangles. As Braak staging is the neuropathology marker showing the strongest association with cognitive performance and decline, these findings could have implication for both AD and AD-related dementias. KEYWORDS: Air pollution, Neurodegenerative outcomes.

Olfactory Bulb Proteomics Reveals Widespread Proteostatic Disturbances in Mixed Dementia and Guides for Potential Serum Biomarkers to Discriminate Alzheimer Disease and Mixed Dementia Phenotypes.

The most common form of mixed dementia (MixD) is constituted by abnormal protein deposits associated with Alzheimer’s disease (AD) that coexist with vascular disease. Although olfactory dysfunction is considered a clinical sign of AD-related dementias, little is known about the impact of this sensorial impairment in MixD at the molecular level. To address this gap in knowledge, we assessed olfactory bulb (OB) proteome-wide expression in MixD subjects (n = 6) respect to neurologically intact controls (n = 7). Around 9% of the quantified proteins were differentially expressed, pinpointing aberrant proteostasis involved in synaptic transmission, nucleoside monophosphate and carbohydrate metabolism, and neuron projection regeneration. In addition, network-driven proteomics revealed a modulation in cell-survival related pathways such as ERK, AKT, and the PDK1-PKC axis. Part of the differential OB protein set was not specific of MixD, also being deregulated across different tauopathies, synucleinopathies, and tardopathies. However, the comparative functional analysis of OB proteome data between MixD and pure AD pathologies deciphered commonalities and differences between both related phenotypes. Finally, olfactory proteomics allowed to propose serum Prolow-density lipoprotein receptor-related protein 1 (LRP1) as a candidate marker to differentiate AD from MixD phenotypes.

Traumatic Brain Injury Exacerbates Alzheimer's Disease Pathology in the Retina of Rats

Alzheimer's disease (AD) is a neurodegenerative condition that affects 5.7 million people in the U.S. alone, representing the leading form of dementia. Additionally, traumatic brain injury (TBI), which can arise from sport concussions, military combat and other causes, is associated with a 2.3-fold higher risk of developing AD and AD-related dementias. Moreover, AD can also lead to visual impairment, and recent studies have found that AD histopathology manifests in the retina, which is an extension of the central nervous system. However, the pathophysiological link between TBI and AD remains poorly understood. In this study we set out to evaluate the effects of TBI, AD, and their combination, on retinal histopathology. Several animal models have been developed to investigate the mechanisms of AD but have been limited by imperfect recapitulation of human pathology. Here we take advantage of a transgenic rat model (Tg-F344) that more faithfully mimics human AD pathology, and subject it to a TBI paradigm. Wild-type and transgenic rats were randomly selected to undergo a unilateral controlled cortical impact (CCI). At 15 months of age, the rats were sacrificed and the eyes subsequently removed, fixed, and processed. Retinas were sectioned and analyzed using immunofluorescent and standard histological staining techniques. Our results confirm the presence of AD markers in transgenic retinas, and an increased severity of AD pathology due to TBI. This has meaningful implications in understanding the pathophysiology of AD in relation to TBI within the retina, which could lead to better treatments and to the development of retinal biomarkers for improved AD diagnosis.

Neuropathology and immune biomarker discovery in a rat model of Alzheimer's disease, TgF344‐AD, with controlled cortical injury model of traumatic brain injury

AbstractBackgroundIndividuals with a history of traumatic brain injury (TBI) have a higher risk of developing Alzheimer’s disease (AD) and AD‐related dementias (ADRD), such as chronic traumatic encephalopathy (CTE). However, the relationship(s) between TBI, AD, and CTE remain poorly understood and markedly understudied. Because transgenic mouse models of AD that develop amyloidosis do not readily develop pathological tauopathy that is commonly found in ADRD, we used the TgF344‐AD transgenic rat model of AD in which amyloid deposition drives endogenous tauopathy and neurodegeneration for our TBI studies.MethodWe used the closed‐head controlled cortical impact (CCI) model of TBI, performed either once (1X‐CCI) or twice over two weeks (2X‐CCI) in both 6‐ and 12‐month‐old TgF344‐AD and wild‐type (F344) rats to investigate the effects of TBI on acute and chronic neuroinflammation, on blood brain barrier (BBB) integrity, and on ADRD‐associated neuropathology. Whole brains and terminal blood draws were collected at different time points following the 1X‐ or 2X‐CCI TBI procedures at 3, 15, 30, 60, and 120 days after the final CCI procedure. Thus, the tissue collection ages of animals across the project allow for TBI‐induced ADRD‐related pathological analyses at 6, 7, 8, 10, 12, 13, 14, and 16 months of age. MRI scans were conducted at 30‐days post‐CCI to examine BBB leakage and chronic inflammation, with subsequent post‐mortem histochemical confirmation. Terminal blood draw samples were used for complete blood cell counts with differential and multiple biomarker analyses.ResultThis project is ongoing, but interim analyses reveal chronic neutrophil percentages remaining consistent in both TgF344‐AD and wild‐type 12‐month‐old cohorts undergoing either 1X‐ or 2X‐CCI at all post‐injury time points. Also, the upright time for the animals does not appear to differ based on impact type or genotype so far. However, histochemical pathological analyses of the 12‐month‐old AD rats have demonstrated changes in Aβ pathology and astrogliosis markers. MRI analyses have not yet been completed.ConclusionWe are continuing to carry out detailed analyses of changes in ADRD‐related pathology and blood biomarkers. These animal models should help provide an increased understanding of chronic neuroinflammation and other pathological mechanisms associated with TBI and risk for ADRD.

Vascular amyloid accumulation alters the gabaergic synapse and induces hyperactivity in a model of cerebral amyloid angiopathy.

ABSTRACTCerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. The mechanisms underlying the contribution of CAA to neurodegeneration are not currently understood. Although CAA is highly associated with the accumulation of β‐amyloid (Aβ), other amyloids are known to associate with the vasculature. Alzheimer's disease (AD) is characterized by parenchymal Aβ deposition and intracellular accumulation of tau as neurofibrillary tangles (NFTs), affecting synapses directly, leading to behavioral and physical impairment. CAA increases with age and is present in 70%–97% of individuals with AD. Studies have overwhelmingly focused on the connection between parenchymal amyloid accumulation and synaptotoxicity; thus, the contribution of vascular amyloid is mostly understudied. Here, synaptic alterations induced by vascular amyloid accumulation and their behavioral consequences were characterized using a mouse model of Familial Danish dementia (FDD), a neurodegenerative disease characterized by the accumulation of Danish amyloid (ADan) in the vasculature. The mouse model (Tg‐FDD) displays a hyperactive phenotype that potentially arises from impairment in the GABAergic synapses, as determined by electrophysiological analysis. We demonstrated that the disruption of GABAergic synapse organization causes this impairment and provided evidence that GABAergic synapses are impaired in patients with CAA pathology. Understanding the mechanism that CAA contributes to synaptic dysfunction in AD‐related dementias is of critical importance for developing future therapeutic interventions.

A1 reactive astrocytes and a loss of TREM2 are associated with an early stage of pathology in a mouse model of cerebral amyloid angiopathy

BackgroundCerebral amyloid angiopathy (CAA) is typified by the cerebrovascular deposition of amyloid. The mechanisms underlying the contribution of CAA to neurodegeneration are not currently understood. Although CAA is highly associated with the accumulation of amyloid beta (Aβ), other amyloids are known to associate with the vasculature. Alzheimer’s disease (AD) is characterized by parenchymal Aβ deposition, intracellular accumulation of tau, and significant neuroinflammation. CAA increases with age and is present in 85–95% of individuals with AD. A substantial amount of research has focused on understanding the connection between parenchymal amyloid and glial activation and neuroinflammation, while associations between vascular amyloid pathology and glial reactivity remain understudied.MethodsHere, we dissect the glial and immune responses associated with early-stage CAA with histological, biochemical, and gene expression analyses in a mouse model of familial Danish dementia (FDD), a neurodegenerative disease characterized by the vascular accumulation of Danish amyloid (ADan). Findings observed in this CAA mouse model were complemented with primary culture assays.ResultsWe demonstrate that early-stage CAA is associated with dysregulation in immune response networks and lipid processing, severe astrogliosis with an A1 astrocytic phenotype, and decreased levels of TREM2 with no reactive microgliosis. Our results also indicate how cholesterol accumulation and ApoE are associated with vascular amyloid deposits at the early stages of pathology. We also demonstrate A1 astrocytic mediation of TREM2 and microglia homeostasis.ConclusionThe initial glial response associated with early-stage CAA is characterized by the upregulation of A1 astrocytes without significant microglial reactivity. Gene expression analysis revealed that several AD risk factors involved in immune response and lipid processing may also play a preponderant role in CAA. This study contributes to the increasing evidence that brain cholesterol metabolism, ApoE, and TREM2 signaling are major players in the pathogenesis of AD-related dementias, including CAA. Understanding the basis for possible differential effects of glial response, ApoE, and TREM2 signaling on parenchymal plaques versus vascular amyloid deposits provides important insight for developing future therapeutic interventions.

Ethical and Regulatory Issues for Embedded Pragmatic Trials Involving People Living with Dementia.

Embedded pragmatic clinical trials (ePCTs) present an opportunity to improve care for people living with dementia (PLWD) and their care partners, but they also generate a complex constellation of ethical and regulatory challenges. These challenges begin with participant identification. Interventions may be delivered in ways that make it difficult to identify who is a human subject and therefore who needs ethical and regulatory protections. The need for informed consent, a core human subjects protection, must be considered but can be in tension with the goals of pragmatic research design. Thus it is essential to consider whether a waiver or alteration of informed consent is justifiable. If informed consent is needed, the question arises of how it should be obtained because researchers must acknowledge the vulnerability of PLWD due in part to diminished capacity and also to increased dependence on others. Further, researchers should recognize that many sites where ePCTs are conducted will be unfamiliar with human subjects research regulations and ethics. In this report, the Regulation and Ethics Core of the National Institute on Aging Imbedded Pragmatic Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory discusses key ethical and regulatory challenges for ePCTs in PLWD. A central thesis is that researchers should strive to anticipate and address these challenges early in the design of their ePCTs as a means of both ensuring compliance and advancing science. J Am Geriatr Soc 68:S37-S42, 2020.

Dissemination and Implementation of Evidence-Based Dementia Care Using Embedded Pragmatic Trials.

There are many nonpharmacologic interventions tested in randomized clinical trials that demonstrate significant benefits for people living with Alzheimer's disease (AD) and AD-related dementia, their care partners, or professional care providers. Nevertheless, with few exceptions, proven interventions have not been translated for delivery in real-world settings, such as home care, primary care, hospitals, community-based services, adult day services, assisted living, nursing homes, or other healthcare systems (HCSs). Using embedded pragmatic clinical trial (ePCT) methods is one approach that can facilitate dissemination and implementation (D&I) of dementia care interventions. The science of D&I can inform the integration of evidence-based dementia care in HCSs by offering theoretical frameworks that capture field complexities and guiding evaluation of implementation processes. Also, D&I science can suggest evidence-based strategies for implementing dementia care in HCSs. Although D&I considerations can inform each stage of dementia care intervention development, it is particularly critical when designing ePCTs. This article examines fundamental considerations for implementing dementia-specific interventions in HCSs and how best to prepare for successful dissemination upstream in the context of ePCTs, thereby illustrating the critical role of the D&I Core of the National Institute on Aging Imbedded Pragmatic Alzheimer's Disease and AD-Related Dementias Clinical Trials Collaboratory. The scientific premise of the D&I Core is that having the "end" in mind, upfront in the design and testing of dementia care programs, can lead to decision-making that optimizes the ultimate goal of wide-scale D&I of evidence-based dementia care programs in HCSs. J Am Geriatr Soc 68:S28-S36, 2020.

Achieving Health Equity in Embedded Pragmatic Trials for People Living with Dementia and Their Family Caregivers.

Embedded pragmatic clinical trials (ePCTs) advance research on Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD) in real-world contexts; however, health equity issues have not yet been fully considered, assessed, or integrated into ePCT designs. Health disparity populations may not be well represented in ePCTs without special efforts to identify and successfully recruit sites of care that serve larger numbers of these populations. The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease (AD) and AD-Related Dementias (AD/ADRD) Clinical Trials (IMPACT) Collaboratory's Health Equity Team will contribute to the overall mission of the collaboratory by developing and implementing strategies to address health equity in the conduct of ePCTs and ensure the collaboratory is a national resource for all Americans with dementia. As a first step toward meeting these goals, this article reviews what is currently known about the inclusion of health disparities populations of people living with dementia (PLWD) and their caregivers in ePCTs, highlights unique challenges related to health equity in the conduct of ePCTs, and suggests priority areas in the design and implementation of ePCTs to increase the awareness and avoidance of pitfalls that may perpetuate and magnify healthcare disparities. J Am Geriatr Soc 68:S8-S13, 2020.

Selecting Outcomes to Ensure Pragmatic Trials Are Relevant to People Living with Dementia.

Outcome measures for embedded pragmatic clinical trials (ePCTs) should reflect the lived experience of people living with dementia (PLWD) and their caregivers, yet patient- and caregiver-reported outcomes (PCROs) are rarely available in large clinical and administrative data sources. Although pragmatic methods may lead to use of existing administrative data rather than new data collected directly from PLWD, interventions are truly impactful only when they change outcomes prioritized by PLWD and their caregivers. The Patient- and Caregiver-Reported Outcomes Core (PCRO Core) of the IMbedded Pragmatic Alzheimer's Disease (AD) and AD-Related Dementias Clinical Trials (IMPACT) Collaboratory aims to promote optimal use of outcomes relevant to PLWD and their caregivers in pragmatic trials. The PCRO Core will address key scientific challenges limiting outcome measurement, such as gaps in existing measures, methodologic constraints, and burdensome data capture. PCRO Core investigators will create a searchable library of AD/AD-related dementias (ADRD) clinical outcome measures, including measures in existing data sources with potential for AD/ADRD ePCTs, and will support best practices in measure development, including pragmatic adaptation of PCROs. Working together with other Cores and Teams within the IMPACT Collaboratory, the PCRO Core will support investigators to select from existing outcome measures, and to innovate in methods for measurement and data capture. In the future, the work of the IMPACT Collaboratory may galvanize broader embedded use of outcomes that matter to PLWD and their care partners in large health systems. J Am Geriatr Soc 68:S55-S61, 2020.

Using Healthcare Data in Embedded Pragmatic Clinical Trials among People Living with Dementia and Their Caregivers: State of the Art.

Embedded pragmatic clinical trials (ePCTs) are embedded in healthcare systems as well as their data environments. For people living with dementia (PLWD), settings of care can be different from the general population and involve additional people whose information is also important. The ePCT designs have the opportunity to leverage data that becomes available through the normal delivery of care. They may be particularly valuable in Alzheimer's disease and Alzheimer's disease-related dementia (AD/ADRD), given the complexity of case identification and the diversity of care settings. Grounded in the objectives of the Data and Technical Core of the newly established National Institute on Aging Imbedded Pragmatic Alzheimer's Disease and AD-Related Dementias Clinical Trials Collaboratory (IMPACT Collaboratory), this article summarizes the state of the art in using existing data sources (eg, Medicare claims, electronic health records) in AD/ADRD ePCTs and approaches to integrating them in real-world settings. J Am Geriatr Soc 68:S49-S54, 2020.

Statistical Considerations for Embedded Pragmatic Clinical Trials in People Living with Dementia.

There is overwhelming need for nonpharmacological interventions to improve the health and well-being of people living with dementia (PLWD). The National Institute on Aging Imbedded Pragmatic Alzheimer's Disease (AD) and AD-Related Dementias Clinical Trials (IMPACT) Collaboratory supports clinical trials of such interventions embedded in healthcare systems. The embedded pragmatic clinical trial (ePCT) is ideally suited to testing the effectiveness of complex interventions in vulnerable populations at the point of care. These trials, however, are complex to conduct and interpret, and face challenges in efficiency (i.e., statistical power) and reproducibility. In addition, trials conducted among PLWD present specific statistical challenges, including difficulty in outcomes ascertainment from PLWD, necessitating reliance on reports by caregivers, and heterogeneity in measurements across different settings or populations. These and other challenges undercut the reliability of measurement, the feasibility of capturing outcomes using pragmatic designs, and the ability to validly estimate interventions' effectiveness in real-world settings. To address these challenges, the IMPACT Collaboratory has convened a Design and Statistics Core, the goals of which are: to support the design and conduct of ePCTs directed toward PLWD and their caregivers; to develop guidance for conducting embedded trials in this population; and to educate quantitative and clinical scientists in the design, conduct, and analysis of these trials. In this article, we discuss some of the contemporary methodological challenges in this area and develop a set of research priorities the Design and Statistics Core will undertake to meet these goals. J Am Geriatr Soc 68:S68-S73, 2020.

Care Is A Basic Human Right

Care Is A Basic Human Right