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The article highlights the U13 Bench-to-Bedside (B2B) conference series, a collaborative effort by the American Geriatrics Society (AGS) and the National Institute on Aging. Topics include the transition of the AGS/National Institute on Aging (NIA) U13 B2B conference series from 2004 to 2017, progressive exploration of key issues in geriatrics reflected in the series of conferences, and an overview of the conferences in the series from 2018 to 2023.

Relationships between patterns of aging-changes in bodyweight and AD are not fully understood. We compared mean age-trajectories of weight between those who did and did not develop late-onset-AD, and evaluated impact of age at maximum weight (AgeMax), and slope of decline in weight, on AD risk. Women with late-onset-AD had lower weight three or more decades before AD onset, and ∼10 years younger AgeMax, compared to AD-free women. APOE4 carriers had younger AgeMax and steeper slope. Older AgeMax and flatter slope predicted lower AD risk. Premature decline in weight could be a sign of accelerated physical aging contributing to AD. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) has recently been linked to cognitive impairment. We hypothesized that AMD modifies the brain aging trajectory, and we conducted a longitudinal diffusion MRI study on 40 participants (20 with AMD and 20 controls) to reveal the location, extent, and dynamics of AMD-related brain changes. Voxel-based analyses at the first visit identified reduced volume in AMD participants in the cuneate gyrus, associated with vision, and the temporal and bilateral cingulate gyrus, linked to higher cognition and memory. The second visit occurred 2 years after the first and revealed that AMD participants had reduced cingulate and superior frontal gyrus volumes, as well as lower fractional anisotropy (FA) for the bilateral occipital lobe, including the visual and the superior frontal cortex. We detected faster rates of volume and FA reduction in AMD participants in the left temporal cortex. We identified inter-lingual and lingual–cerebellar connections as important differentiators in AMD participants. Bundle analyses revealed that the lingual gyrus had a lower streamline length in the AMD participants at the first visit, indicating a connection between retinal and brain health. FA differences in select inter-lingual and lingual cerebellar bundles at the second visit showed downstream effects of vision loss. Our analyses revealed widespread changes in AMD participants, beyond brain networks directly involved in vision processing. [ABSTRACT FROM AUTHOR]

Interventions to preserve functional independence in older adults are critically needed to optimize ‘successful aging’ among the large and increasing population of older adults in the United States. For most aging adults, the management of chronic diseases is the most common and impactful risk factor for loss of functional independence. Chronic disease management inherently involves the learning and adaptation of new behaviors, such as adopting or modifying physical activity habits and managing weight. Despite the importance of chronic disease management in older adults, vanishingly few individuals optimally manage their health behavior in the service of chronic disease stabilization to preserve functional independence. Contemporary conceptual models of chronic disease management and health habit theory suggest that this lack of optimal management may result from an underappreciated distinction within the health behavior literature: the behavioral domains critical for initiation of new behaviors (Initiation Phase) are largely distinct from those that facilitate their maintenance (Maintenance Phase). Psychological factors, particularly experiential acceptance and trait levels of openness are critical to engagement with new health behaviors, willingness to make difficult lifestyle changes, and the ability to tolerate aversive affective responses in the process. Cognitive factors, particularly executive function, are critical to learning new skills, using them effectively across different areas of life and contextual demands, and updating of skills to facilitate behavioral maintenance. Emerging data therefore suggests that individuals with greater executive function are better able to sustain behavior changes, which in turn protects against cognitive decline. In addition, social and structural supports of behavior change serve a critical buffering role across phases of behavior change. The present review attempts to address these gaps by proposing a novel biobehavioral intervention framework that incorporates both individual-level and social support system-level variables for the purpose of treatment tailoring. Our intervention framework triangulates on the central importance of self-regulatory functioning, proposing that both cognitive and psychological mechanisms ultimately influence an individuals’ ability to engage in different aspects of self-management (individual level) in the service of maintaining independence. Importantly, the proposed linkages of cognitive and affective functioning align with emerging individual difference frameworks, suggesting that lower levels of cognitive and/or psychological flexibility represent an intermediate phenotype of risk. Individuals exhibiting selfregulatory lapses either due to the inability to regulate their emotional responses or due to the presence of executive functioning impairments are therefore the most likely to require assistance to preserve functional independence. In addition, these vulnerabilities will be more easily observable for individuals requiring greater complexity of self-management behavioral demands (e.g. complexity of medication regimen) and/or with lesser social support. Our proposed framework also intuits several distinct intervention pathways based on the profile of selfregulatory behaviors: we propose that individuals with intact affect regulation and impaired executive function will preferentially respond to ‘top-down’ training approaches (e.g., strategy and process work). Individuals with intact executive function and impaired affect regulation will respond to ‘bottom-up’ approaches (e.g., graded exposure). And individuals with impairments in both may require treatments targeting caregiving or structural supports, particularly in the context of elevated behavioral demands. [ABSTRACT FROM AUTHOR]

Dysregulation of physiological processes may contribute to Alzheimer’s disease (AD) development. We previously found that an increase in the level of physiological dysregulation (PD) in the aging body is associated with declining resilience and robustness to major diseases. Also, our genome-wide association study found that genes associated with the age-related increase in PD frequently represented pathways implicated in axon guidance and synaptic function, which in turn were linked to AD and related traits (e.g., amyloid, tau, neurodegeneration) in the literature. Here, we tested the hypothesis that genes involved in PD and axon guidance/synapse function may jointly influence onset of AD. We assessed the impact of interactions between SNPs in such genes on AD onset in the Long Life Family Study and sought to replicate the findings in the Health and Retirement Study. We found significant interactions between SNPs in the UNC5C and CNTN6, and PLXNA4 and EPHB2 genes that influenced AD onset in both datasets. Associations with individual SNPs were not statistically significant. Our findings, thus, support a major role of genetic interactions in the heterogeneity of AD and suggest the joint contribution of genes involved in PD and axon guidance/synapse function (essential for the maintenance of complex neural networks) to AD development. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This report summarizes the presentations, discussions, and recommendations of the most recent American Geriatrics Society and National Institute on Aging research conference, "Cancer and Cardiovascular Disease," on October 18–19, 2021. The purpose of this virtual meeting was to address the interface between cancer and heart disease, which are the two leading causes of death among older Americans. Age‐related physiologic changes are implicated in the pathogenesis of both conditions. Emerging data suggest that cancer‐related cardiovascular disease (CVD) involves disrupted cell signaling and cellular senescence. The risk factors for CVD are also risk factors for cancer and an increased likelihood of cancer death, and people who have both cancer and CVD do more poorly than those who have only cancer or only CVD. Issues addressed in this bench‐to‐bedside conference include mechanisms of cancer and CVD co‐development in older adults, cardiotoxic effects of cancer therapy, and management of comorbid cancer and CVD. Presenters discussed approaches to ensure equitable access to clinical trials and health care for diverse populations of adults with CVD and cancer, mechanisms of cancer therapy cardiotoxicity, and management of comorbid CVD and cancer, including the role of patient values and preferences in treatment decisions. Workshop participants identified many research gaps and questions that could lead to an enhanced understanding of comorbid CVD and cancer and to better and more equitable management strategies. [ABSTRACT FROM AUTHOR]