December 30, 2021
PAR-22-093 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)
PAR-22-094 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R21 Clinical Trial Optional)
National Institute on Aging (NIA)
Alzheimer’s disease (AD) is a progressive, degenerative disorder of the brain and is the most common form of dementia in older adults. Prominent behavioral manifestations of AD include memory impairments and decline in other cognitive domains. Age is a major risk factor for developing dementia, with imaging and biomarker data suggesting that the pathophysiological processes of AD begin more than a decade prior to the diagnosis of dementia. AD is a heterogeneous, multifactorial disease, and a challenge in AD research is to fully understand how the multiple etiologies and age-related prodromal processes contribute to the pathophysiology of AD. Knowledge of the mechanisms underlying the shift from healthy brain aging to the neurodegeneration of AD is imperative for the design and determination of effective interventions.
Changes in brain structure and function may continue throughout life, and studies at multiple levels of analysis in model organisms and humans are helping to define the normal trajectory of changes in the brain over the adult lifespan. Structural neuroimaging and anatomical studies of brain have shown declines in total gray and white matter, along with shrinkage or atrophy and synaptic changes in certain regions of the brain during aging. Functional imaging studies are defining the workings of large-scale neural and cognitive networks in the aging human brain, and have shown, for example, disruption of the resting-state default mode network, as well as putative compensatory recruitment of brain areas to sustain cognitive function. Human and animal studies suggest that adaptive or resilient processes (i.e., brain plasticity) may be needed for maintenance of brain structure and function during normal aging. At the molecular and cellular level of analysis in animal models, brain aging is associated with changes in gene and epigenetic expression, mitochondrial and energy metabolism, calcium regulation, protein homeostasis, glia, and neural plasticity and synaptic function. What remains unclear is when these normal aging changes transition to pathological aging and disease phenotypes. Complicating the understanding of the role of aging in AD is the fact that most studies employ adult, not aged, genetic animal models of disease. Integration of research at various levels of analysis, from cells to neural networks, in older adults and in appropriate animal and cell models is needed to reach a global understanding of brain aging and its contribution to, and promotion of, pathological processes underlying AD.
The goal of this Notice of Special Interest (NOSI) is to solicit applications that aim to establish the role and underlying mechanisms by which brain aging impacts the development and progression of AD. A comprehensive and integrative characterization of brain aging, including its crosstalk with peripheral systems and factors, will help to define the mechanisms underlying the shift from normal aging to pathological processes in the etiology of AD. To gain a deeper understanding of the complex biology and physiology of healthy and pathologic brain aging, cross-disciplinary, systems-based approaches using newly developed tools and technology to integrate findings on AD with research on the basic biology and neurobiology of aging are encouraged. Animal and human studies are appropriate for this NOSI.
Areas of research interest and opportunity include, but are not limited to, the following:
Application and Submission Information
This notice applies to due dates on or after March 11, 2022 and subsequent receipt dates through November 13, 2024.
Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcement through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
National Institute on Aging (NIA)