Notice of Special Interest (NOSI): Sensory and Motor System Changes as Predictors of Preclinical Alzheimer’s Disease.
Notice Number:

Key Dates

Release Date:

January 6, 2022

First Available Due Date:
March 11, 2022
Expiration Date:
November 13, 2024

Related Announcements

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)

Issued by

National Institute on Aging (NIA)


The purpose of this Notice of Special Interest (NOSI) is to encourage applications that propose either basic, clinical, or a combination of basic and clinical studies that investigate how functional changes in the sensory and/or motor systems impact the development and progression of Alzheimer’s disease.


Alzheimer’s disease (AD) continues to be a critical health problem as the aging population grows. Over six million Americans age 65 and older are living with AD, and it is projected that the number of new cases of AD will double by 2025. The neuropathological hallmarks of AD, including amyloid-beta accumulation, tau aggregation, and neurofibrillary tangles may accumulate years before the cognitive symptoms become apparent. Based on these observations, intervening prior to detection of cognitive impairment might present an opportunity to modify the disease and decrease the risk of future cognitive decline. To this end, there have been significant efforts to identify and develop reliable biomarkers of early or preclinical AD.

Over the last decade there has been growing interest in non-cognitive functional changes, such as sensory or motor changes, as potential predictors or biomarkers of preclinical AD. Evidence from epidemiological studies suggest that changes in olfaction, audition, and even gait speed may precede the onset of cognitive impairment and dementia by several years. Studies have also shown that sensory and motor regions of the central nervous system (CNS) are affected by AD pathology. For example, AD pathology is found in the olfactory neural networks, visual system neural pathways, and motor neurons of the pyramidal and extrapyramidal motor pathways in AD patients. Additionally, AD pathology has been shown to appear in sensory association areas well before its appearance in regions involving memory, such as the entorhinal and hippocampal areas. However, despite the mounting evidence, sensory and motor changes have not gained much traction as biomarkers of preclinical AD primarily due to their lack of specificity. Sensory and motor changes are very common in healthy aging as well as other neurodegenerative diseases. While some data suggest that assessment of multiple sensory and/or motor modalities in conjunction with other molecular, genetic, or imaging biomarkers may improve the diagnostic accuracy of preclinical AD, more research is needed. Further investigation is also needed to disentangle the sensory and motor changes associated with AD from those associated with healthy aging to harness their potential as early, non-invasive AD biomarkers.

Research Objectives

This NOSI encourages applications investigating how functional changes in sensory systems (e.g., olfactory, visual, auditory, somatosensory, gustatory) and/or motor systems impact the development and progression of AD. Applications proposing to distinguish the sensory and/or motor changes associated with early AD from those associated with normal aging are also highly encouraged. Studies may include older adults and/or animal models and may employ a variety of approaches—including cellular, molecular, imaging, physiological, and genetic—to address this need. For clinical studies, leveraging of existing longitudinal cohorts already collecting sensory and/or motor assessments is highly encouraged. Studies proposing to establish new cohorts must present a strong justification for why this is needed.

Studies of interest may include, but are not limited to, the following:

  • Mechanistic studies to understand if and how early AD pathology in sensory and/or motor areas of the CNS can contribute to decline in sensory/motor function
  • Studies that aim to understand the etiology of sensory and motor dysfunctions in preclinical AD
  • Neuroimaging studies to investigate changes in brain networks that result from changes in sensory and/or motor function in preclinical AD
  • Mechanistic studies using well established animal models of AD to further understand how sensory and/or motor changes may impact preclinical AD at the circuit level
  • Studies that aim to understand the molecular and cellular mechanisms by which sensory and motor system changes underlie the pathogenesis of AD
  • Clinical studies combining sensory and/or motor system measures with other molecular, genetic, and/or imaging biomarkers of AD risk to identify a battery that might predict conversion to AD
  • Studies that distinguish sensory and/or motor changes associated with early AD from those associated with healthy aging

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.

  • 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)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-AG-21-044” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Coryse St. Hillaire-Clarke, Ph.D.
National Institute on Aging (NIA)
Phone: 301-827-6944