NIH – Emotional Function in Normal Aging and/or MCI and AD/ADRD (R01, R21 Clinical Trial Optional)

January 16, 2018 by School of Medicine Webmaster

The following description was taken from the R01 version of this FOA.

The National Institute on Aging (NIA) has supported foundational research on emotional function in aging, which suggests that, for most adults, normal aging is associated with general trends toward improved emotion regulation (increasing positive and decreasing negative affect, greater emotional stability, higher life satisfaction, a “positivity” bias in information processing). This new funding opportunity underscores NIA’s continued commitment to research in age-related changes in emotional function and provides an opportunity to address remaining gaps in the study of emotional function in normal aging, as well as to extend this work beyond normal aging, to MCI and AD/ADRD.

Evidence suggests that, compared with younger adults, older adults often show superior emotion regulation capacities, employ different strategies for executive control of emotional information, and recruit different neural networks in performing affective tasks. Such patterns have been variously hypothesized to stem from increased motivation to maintain emotional well-being, learning more skillful and efficient emotion processing strategies, or compensatory adaptations to age-related brain changes. However, not all adults demonstrate the positive emotion regulation profiles that characterize adaptive aging. To date, there has been little mechanistic research focused on sources of individual variability in development and maturation of emotional regulatory functions or other aspects of emotional functioning. Thus, the psychological, behavioral, physiological, and neurobiological processes that account for variation in this age-related emotional adaptation remain poorly understood.

In addition, there has been little scientific investigation of the extent to which adults with MCI or AD/ADRD manifest or fail to show normative maturational shifts, or at what point(s) during the adult lifespan they may tend to diverge in emotion regulation trajectories. NIA seeks to stimulate new research that further elucidates the behavioral, psychological, physiological, and neurobiological trajectories of normal age-related change in affective function, as well as research that examines divergence from that normal trajectory in MCI and AD/ADRD.

It is also paradoxical that, despite a normative course of cognitive decline with age, many aspects of emotional function improve with age. Though attributed to improved emotional regulatory strategies, such strategies are believed to rely on the same cognitive control capacities that decline with aging. Numerous questions remain regarding the role of cognitive control in adaptive emotional aging, alternative strategies that older adults might employ to regulate emotion, the cognitive processes that undergird those strategies, and the causes of individual variation in the ability to engage these strategies with advancing age.

Research Objectives

NIA seeks to stimulate new research that further elucidates the behavioral, psychological, physiological, and neurobiological trajectories of normal age-related change in affective function, as well as research that examines divergence from that normal trajectory in MCI and AD/ADRD. There is also a need for research to elucidate the neural, behavioral, and psychological mechanisms involved in the emotional dysfunction that characterizes neuropsychiatric symptoms in AD/ADRD.

Ideally, the studies proposed will examine multiple domains of emotional function to address the dynamic interactions among differentially maturing brain systems and psychological processes that determine normative trajectories of emotional aging. Additional studies will support mechanistic research on how age-related changes in emotion processing occur, and interact with neurobiological and neurobehavioral factors associated with MCI and AD/ADRD and account for the emergence of emotional changes and/or affective dysregulation in these disorders.

NIA is also interested in descriptive epidemiology employing longitudinal cohort studies to estimate adult neurodevelopmental changes relevant to emotion regulation processes and other aspects of emotional function. Specifically, research is needed to clarify points in the adult life course at which trajectories diverge for subgroups with successful cognitive aging, normative cognitive decline, MCI, and AD/ADRD; identifying both when trajectories diverge, and in which psychological and neurobiological processes.

In addition, NIA is interested in studies that (1) test the extent to which cognitive or motivational changes account for age differences in emotion regulation; (2) test the hypothesis that biases in attention or memory serve the purpose of regulating emotion; and (3) identify the strategies that confer success in emotion regulation and the contexts that undermine success. There is also a need for validation studies connecting lab paradigms to real world contexts.

NIA particularly encourages more research that attends to social, financial, and health inequalities in trajectories of emotional development through adulthood. This will involve recruiting more diverse samples to address the links between social and financial inequality and late-life emotional function. Finally, a life course perspective on this issue would help link the substantial developmental research on affective processes in childhood with that on aging. Both approaches have the potential to strengthen life-span developmental theories about age-related emotional change.

In AD/ADRD research, there is an unmet need for studies of the affective problems in patients that present some of the greatest challenges to caregivers, nursing staff, and family members: the dysregulation of patients’ negative emotions (neuropsychiatric symptoms) including irritability, anger, melancholia, anhedonia, paranoia, and fear. These emotional states are difficult to manage clinically, often result in over-medication, and potentially result in social isolation, because they are so difficult for caregivers to handle. There is emerging evidence that precursors of these neuropsychiatric symptoms may be evident prior to onset of cognitive impairment, and may signal the earliest stages of disease. To date, there has been little attention in the field of affective science to these early psychological and behavioral changes (mild behavioral impairment) or to the neuropsychiatric symptoms that characterize more advanced AD/ADRD.

Mechanistic research is encouraged that assesses emotional processes dimensionally, integrating across multiple levels of analysis and employing cutting-edge methodology from such fields as social cognitive and affective neuroscience, psychoneuroimmunology, psychosomatic medicine, neuroimaging, neurophysiology, gene expression and epigenetics, neuroendocrinology, and lifespan developmental psychology. Mechanisms that account for adaptive or maladaptive affective function may be characterized at any level of analysis from molecular to social. Use of psychometrically sound assessment approaches is encouraged, as well as direct observation of emotion processes, such as in response to emotion-evoking stimuli, situations, or scenarios. Ideally, the studies proposed will examine multiple domains of emotion processing to address, in aging adults, the key developmental concept of dynamic interactions among behavioral and brain systems that support successful (and unsuccessful) emotion function.

The particular adult age ranges over which maturational changes may be examined are not prespecified and should be determined to fit the specific research questions posed. Applicants are expected to provide compelling rationales for their age range selection. Applications may propose to include data spanning the full life course, provided the research questions posed are relevant to adult maturational and aging processes.

Applications may also propose work using animal models of age-related changes in emotional function, particularly those that hold potential for elucidating the role of early environments and exposures in shaping trajectories of emotional function over the life course. Projects proposing research in animal models should clearly articulate the relevance to human aging.

Specific Areas of Research Interest

Areas of interest include, but are not limited to:

  • Studies of affective regulation and associated behavioral, psychological, physiological, and neurobiological factors across the adult age span, and clarifying points in the adult life course at which trajectories may diverge for different subgroups;
  • Studies to clarify points in the adult life course at which trajectories diverge for subgroups with successful cognitive aging, normative cognitive decline, MCI, and AD/ADRD, identifying both when trajectories diverge, and in which psychological and neurobiological processes;
  • Studies that clarify how dysfunction in behavioral, psychological, physiological, and neurobiological processes related to affective function might account for any of the neuropsychiatric symptoms observed in AD/ADRD;
  • Studies that integrate observational and experimental approaches to examine how normative age-related affective function manifests in real-world contexts;
  • Studies that clarify/resolve the paradox of age-related improvement in emotional regulation in the face of age-related cognitive decline;
  • Secondary analysis of or new data collection in life-span studies with assessments of emotional and cognitive function from early life, including studies that examine the impact of early adversity on maturation of adult affect regulation;
  • Studies of emotional function in samples representing population variation in social and financial circumstances, to permit examination of the link between socioeconomic inequality and later life emotional development;
  • Studies evaluating differences in the brain circuits or cortical areas recruited during emotional challenge or task performance as a function of age and whether such differences predict resilience against onset of disrupted affective symptoms in MCI or AD/ADRD or deterioration in those functions in these disorders; and
  • Studies employing efficient multi-cohort designs to estimate adult neurodevelopmental changes relevant to emotion regulation processes.

Mechanistic Stage 0 (basic research) or Stage I (intervention modification/development) clinical trials are appropriate for this FOA. The full NIH Stage Model is outlined and described here: NIH Stage Model. See information about the new NIH clinical trial definition at https://osp.od.nih.gov/clinical-research/clinical-trials/.) Trials or experiments designed for the purpose of changing emotional function should be designed to test hypotheses about mechanisms of action for the given intervention/manipulation. Approaches should be in line with the mechanisms-focused, experimental medicine approach compatible with the NIH Stage Model and defined and supported by the NIH Common Fund’s Science of Behavior Change (SOBC) program. The experimental medicine approach to behavior change research encourages clear, a priori specification of the intended behavioral, psychological, physiological, or neurobiological target(s) of an intervention, and methods that test the degree to which an experimental manipulation or intervention engages those targets. The SOBC program describes four steps involved in the experimental medicine approach: 1) identifying one or more hypothesized intervention targets; 2) attempting to engage the target(s) through experimentation or intervention; 3) measuring the degree to which the experimental manipulation or intervention actually engaged the hypothesized target(s); and 4) testing the degree to which target engagement produces the desired change in health behaviors or clinical outcomes. For more information about the SOBC program, please see: https://commonfund.nih.gov/behaviorchange.

Deadlines:  standard dates apply

URLs:

  • R01 – https://grants.nih.gov/grants/guide/pa-files/PAR-18-581.html
  • R21 – https://grants.nih.gov/grants/guide/pa-files/PAR-18-582.html

Filed Under: Funding Opportunities