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1.
Sci Rep ; 14(1): 15036, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38951633

RESUMEN

Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.


Asunto(s)
Enfermedad de Alzheimer , Ensayos Clínicos como Asunto , Selección de Paciente , Humanos , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/epidemiología , Demencia/epidemiología , Determinación de la Elegibilidad , Etnicidad , National Institute on Aging (U.S.) , Estados Unidos/epidemiología , Negro o Afroamericano , Hispánicos o Latinos , Indio Americano o Nativo de Alaska , Nativos de Hawái y Otras Islas del Pacífico
5.
J Am Geriatr Soc ; 72(5): 1574-1582, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38445895

RESUMEN

The National Institute on Aging (NIA), part of the National Institutes of Health (NIH), was founded in 1974 to support and conduct research on aging and the health and well-being of older adults. Fifty years ago, the concept of studying aging generated much skepticism. Early NIA-funded research findings helped establish the great value of aging research and provided the foundation for significant science advances that have improved our understanding of the aging process, diseases and conditions associated with aging, and the effects of health inequities, as well as the need to promote healthy aging lifestyles. Today, we celebrate the many important contributions to aging research made possible by NIA, as well as opportunities to continue to make meaningful progress. NIA emphasizes that the broad aging research community must continue to increase and expand our collective efforts to recruit and train a diverse next generation of aging researchers.


Asunto(s)
Envejecimiento , Aniversarios y Eventos Especiales , Investigación Biomédica , National Institute on Aging (U.S.) , Humanos , Estados Unidos , Anciano , Envejecimiento/fisiología , Investigación Biomédica/historia , Historia del Siglo XX , Historia del Siglo XXI , Envejecimiento Saludable , Geriatría/historia
8.
Alzheimers Dement ; 20(4): 3088-3098, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38348782

RESUMEN

INTRODUCTION: Older military veterans often present with unique and complex risk factors for Alzheimer's disease (AD) and related dementias. Increasing veteran participation in research studies offers one avenue to advance the field and improve health outcomes. METHODS: To this end, the National Institute on Aging (NIA) and Department of Veterans Affairs (VA) partnered to build infrastructure, improve collaboration, and intensify targeted recruitment of veterans. This initiative, INviting Veterans InTo Enrollment in Alzheimer's Disease Research Centers (INVITE-ADRC), provided funding for five sites and cross-site organizing structure. Diverse and innovative recruitment strategies were used. RESULTS: Across five sites, 172 veterans entered registries, and 99 were enrolled into ADRC studies. Of the enrolled, 39 were veterans from historically underrepresented racial and ethnic groups. CONCLUSIONS: This initiative laid the groundwork to establish sustainable relationships between the VA and ADRCs. The partnership between both federal agencies demonstrates how mutual interests can accelerate progress. In turn, efforts can help our aging veterans.


Asunto(s)
Enfermedad de Alzheimer , Veteranos , Estados Unidos , Humanos , National Institute on Aging (U.S.) , United States Department of Veterans Affairs , Envejecimiento
11.
Ann Neurol ; 95(4): 625-634, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38180638

RESUMEN

Alzheimer's disease (AD) is the most common neurodegenerative disorder and one of the leading causes of disability worldwide. The apolipoprotein E4 gene (APOE4) is the strongest genetic risk factor for AD. In 2023, the APOE4 National Institute on Aging/Alzheimer's Disease Sequencing Project working group came together to gather data and discuss the question of whether to reduce or increase APOE4 as a therapeutic intervention for AD. It was the unanimous consensus that cumulative data from multiple studies in humans and animal models support that lowering APOE4 should be a target for therapeutic approaches for APOE4 carriers. ANN NEUROL 2024;95:625-634.


Asunto(s)
Enfermedad de Alzheimer , Animales , Estados Unidos , Humanos , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/tratamiento farmacológico , Apolipoproteína E4/genética , Objetivos , National Institute on Aging (U.S.)
12.
Alzheimers Dement ; 20(2): 1123-1136, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37881831

RESUMEN

INTRODUCTION: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site Alzheimer's Genomics Database (GenomicsDB) is a public knowledge base of Alzheimer's disease (AD) genetic datasets and genomic annotations. METHODS: GenomicsDB uses a custom systems architecture to adopt and enforce rigorous standards that facilitate harmonization of AD-relevant genome-wide association study summary statistics datasets with functional annotations, including over 230 million annotated variants from the AD Sequencing Project. RESULTS: GenomicsDB generates interactive reports compiled from the harmonized datasets and annotations. These reports contextualize AD-risk associations in a broader functional genomic setting and summarize them in the context of functionally annotated genes and variants. DISCUSSION: Created to make AD-genetics knowledge more accessible to AD researchers, the GenomicsDB is designed to guide users unfamiliar with genetic data in not only exploring but also interpreting this ever-growing volume of data. Scalable and interoperable with other genomics resources using data technology standards, the GenomicsDB can serve as a central hub for research and data analysis on AD and related dementias. HIGHLIGHTS: The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) offers to the public a unique, disease-centric collection of AD-relevant GWAS summary statistics datasets. Interpreting these data is challenging and requires significant bioinformatics expertise to standardize datasets and harmonize them with functional annotations on genome-wide scales. The NIAGADS Alzheimer's GenomicsDB helps overcome these challenges by providing a user-friendly public knowledge base for AD-relevant genetics that shares harmonized, annotated summary statistics datasets from the NIAGADS repository in an interpretable, easily searchable format.


Asunto(s)
Enfermedad de Alzheimer , Estados Unidos , Humanos , Enfermedad de Alzheimer/genética , Estudio de Asociación del Genoma Completo , National Institute on Aging (U.S.) , Genómica , Bases de Datos Factuales , Predisposición Genética a la Enfermedad/genética
13.
J Gerontol A Biol Sci Med Sci ; 78(Suppl 1): 53-60, 2023 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-37325957

RESUMEN

The geroscience hypothesis posits that by targeting key hallmarks of aging we may simultaneously prevent or delay several age-related diseases and thereby increase healthspan, or life span spent free of significant disease and disability. Studies are underway to examine several possible pharmacological interventions for this purpose. As part of a National Institute on Aging workshop on the development of function-promoting therapies, scientific content experts provided literature reviews and state-of-the-field assessments for the studies of senolytics, nicotinamide adenine dinucleotide (NAD+) boosters, and metformin. Cellular senescence increases with age, and preclinical studies demonstrate that the use of senolytic drugs improves healthspan in rodents. Human studies using senolytics are in progress. NAD+ and its phosphorylated form, NADP+, play vital roles in metabolism and cellular signaling. Increasing NAD+ by supplementation with precursors including nicotinamide riboside and nicotinamide mononucleotide appears to extend healthspan in model organisms, but human studies are limited and results are mixed. Metformin is a biguanide widely used for glucose lowering, which is believed to have pleiotropic effects targeting several hallmarks of aging. Preclinical studies suggest it improves life span and healthspan, and observational studies suggest benefits for the prevention of several age-related diseases. Clinical trials are underway to examine metformin for healthspan and frailty prevention. Preclinical and emerging clinical studies suggest there is potential to improve healthspan through the use of pharmacologic agents reviewed. However, much further research is needed to demonstrate benefits and general safety for wider use, the appropriate target populations, and longer-term outcomes.


Asunto(s)
Metformina , NAD , Estados Unidos , Humanos , National Institute on Aging (U.S.) , Senoterapéuticos , Envejecimiento , Metformina/farmacología
14.
J Gerontol A Biol Sci Med Sci ; 78(10): 1733-1739, 2023 10 09.
Artículo en Inglés | MEDLINE | ID: mdl-37148367

RESUMEN

The National Institute on Aging sponsored a symposium at the Gerontological Society of America (GSA) annual meeting in Indianapolis, Indiana, to discuss recent discoveries related to senescent and inflammatory mechanisms in aging and disease. Consistent with the 2022 Biological Sciences GSA program led by Dr. Rozalyn Anderson, the symposium featured early-stage investigators and a leader in the field of geroscience research. Cell senescence and immune interactions coordinate homeostatic and protective programming throughout the life span. Dysfunctional communication in this exchange eventuates in inflammation-related compositional changes in aged tissues, including propagation of the senescence-associated secretory phenotype and accumulation of senescent and exhausted immune cells. Presentations in this symposium explored senescent and immune-related dysfunction in aging from diverse viewpoints and featured emerging cellular and molecular methods. A central takeaway from the event was that the use of new models and approaches, including single-cell -omics, novel mouse models, and 3D culture systems, is revealing dynamic properties and interactions of senescent and immune cell fates. This knowledge is critical for devising new therapeutic approaches with important translational relevance.


Asunto(s)
Envejecimiento , National Institute on Aging (U.S.) , Animales , Estados Unidos , Ratones , Fenotipo , Senescencia Celular , Inflamación
15.
J Am Geriatr Soc ; 71(8): 2381-2392, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37079440

RESUMEN

Resilience, which relates to one's ability to respond to stressors, typically declines with age and the development of comorbid conditions in older organisms. Although progress has been made to improve our understanding of resilience in older adults, disciplines have employed different frameworks and definitions to study various aspects of older adults' response to acute or chronic stressors. "Overview of the Resilience World: State of the Science," a bench-to-bedside conference on October 12-13, 2022, was sponsored by the American Geriatrics Society and National Institute on Aging. This conference, summarized in this report, explored commonalities and differences among the frameworks of resilience most commonly used in aging research in the three domains of resilience: physical, cognitive, and psychosocial. These three main domains are intertwined, and stressors in one domain can lead to effects in other domains. The themes of the conference sessions included underlying contributors to resilience, the dynamic nature of resilience throughout the life span, and the role of resilience in health equity. Although participants did not agree on a single definition of "resilience(s)," they identified common core elements of a definition that can be applied to all domains and noted unique features that are domain specific. The presentations and discussions led to recommendations for new longitudinal studies of the impact of exposures to stressors on resilience in older adults, the use of new and existing cohort study data, natural experiments (including the COVID-19 pandemic), and preclinical models for resilience research, as well as translational research to bring findings on resilience to patient care.


Asunto(s)
COVID-19 , Geriatría , Humanos , Estados Unidos , Anciano , Envejecimiento/fisiología , National Institute on Aging (U.S.) , Estudios de Cohortes , Pandemias
16.
Artículo en Inglés | MEDLINE | ID: mdl-36878648

RESUMEN

The conceptualization of the field of geroscience, which began about 10 years ago, marks, together with the publication of "The hallmarks of aging" (see López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Cell 153: 1194-1217, 2013), a significant watershed in the development of aging research. Based on a very simple and commonly accepted premise, namely, that aging biology is at the core the most significant risk factor for all chronic diseases affecting the elderly, geroscience became possible because of earlier significant developments in the field of aging biology. Here we describe the origins of the concept, as well as its current status in the field. The principles of geroscience provide an important new biomedical perspective and have spawned a significantly increased interest in aging biology within the larger biomedical scientific community.


Asunto(s)
Investigación Biomédica , Gerociencia , Estados Unidos , Humanos , Anciano , National Institute on Aging (U.S.) , Envejecimiento , Enfermedad Crónica
17.
J Alzheimers Dis ; 92(3): 729-740, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36806503

RESUMEN

Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) research has advanced gene and biomarker technologies to aid identification of individuals at risk for dementia. This innovation is a lynchpin in development of disease-modifying therapies. The emerging science could transform outcomes for patients and families. However, current limitations in the racial representation and inclusion of racial diversity in research limits the relevance of these technologies: AD/ADRD research cohorts used to define biomarker cutoffs are mostly White, despite clinical and epidemiologic research that shows Black populations are among those experiencing the greatest burdens of AD/ADRD. White cohorts alone are insufficient to characterize heterogeneity in disease and in life experiences that can alter AD/ADRD's courses. The National Institute on Aging (NIA) has called for increased racial diversity in AD/ADRD research. While scientists are working to implement NIA's plan to build more diverse research cohorts, they are also seeking out opportunities to consider race in AD/ADRD research. Recently, scientists have posed two ways of including race in AD/ADRD research: ancestry-based verification of race and race-based adjustment of biomarker test results. Both warrant careful examination for how they are impacting AD/ADRD science with respect to specific study objectives and the broader mission of the field. If these research methods are not grounded in pursuit of equity and justice, biases they introduce into AD/ADRD science could perpetuate, or even worsen, disparities in AD/ADRD research and care.


Asunto(s)
Enfermedad de Alzheimer , Demencia , Humanos , Enfermedad de Alzheimer/etnología , Biomarcadores , National Institute on Aging (U.S.) , Estados Unidos/epidemiología , Negro o Afroamericano , Demencia/etnología , Blanco
19.
Exp Gerontol ; 173: 112102, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36693530

RESUMEN

Changes in old age that contribute to the complex issue of an increased metabolic cost of walking (mass-specific energy cost per unit distance traveled) in older adults appear to center at least in part on changes in gait biomechanics. However, age-related changes in energy metabolism, neuromuscular function and connective tissue properties also likely contribute to this problem, of which the consequences are poor mobility and increased risk of inactivity-related disease and disability. The U.S. National Institute on Aging convened a workshop in September 2021 with an interdisciplinary group of scientists to address the gaps in research related to the mechanisms and consequences of changes in mobility in old age. The goal of the workshop was to identify promising ways to move the field forward toward improving gait performance, decreasing energy cost, and enhancing mobility for older adults. This report summarizes the workshop and brings multidisciplinary insight into the known and potential causes and consequences of age-related changes in gait biomechanics. We highlight how gait mechanics and energy cost change with aging, the potential neuromuscular mechanisms and role of connective tissue in these changes, and cutting-edge interventions and technologies that may be used to measure and improve gait and mobility in older adults. Key gaps in the literature that warrant targeted research in the future are identified and discussed.


Asunto(s)
National Institute on Aging (U.S.) , Caminata , Estados Unidos , Fenómenos Biomecánicos , Marcha
20.
Gerontol Geriatr Educ ; 44(3): 466-479, 2023 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-35815534

RESUMEN

The development of a skilled research workforce in aging is fundamental to understanding conditions associated with growing older and extending healthy, active years of life. The National Institutes of Health (NIH) supports the training of health scientists, and its National Institute on Aging (NIA) prioritizes the professional development of investigators with an interest in aging. Since 1987, NIA's Summer Institute on Aging Research, renamed the Butler-Williams (B-W) Scholars Program in 2013, has offered an intensive one-week experience on issues, opportunities, and challenges of research on aging, with emphasis on disparities and health equity. The first 30 years of the Program are described in this report, including its history, selected curriculum highlights, Scholar outcomes, and qualitative data from faculty, and the program's impact on the training, growth, and development of scientists in aging research. Questions raised over a decade ago by the Committee on the Future Health Care Workforce for Older Americans Board on Health Care Services are revisited, and recommendations for the future are provided. This important Program remains an exemplar for the training and development of health scientists for careers that advance biomedical research and emphasize an equitable understanding of factors related to extending healthy years of life.


Asunto(s)
Investigación Biomédica , Geriatría , Humanos , Estados Unidos , Anciano , National Institute on Aging (U.S.) , Geriatría/educación , Envejecimiento , Curriculum
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