The purpose of this Funding Opportunity Announcement (FOA) is to encourage applications that propose either basic, clinical, or a combination of basic and clinical studies to investigate how functional changes in the sensory and/or motor systems impact the development and progression of Alzheimer’s disease. 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 motor assessments is highly encouraged.
Alzheimer’s disease (AD) continues to be a critical health problem as the aging population grows. Approximately five million Americans age 65 and older suffer from 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 CNS are affected by AD pathology. For example, AD pathology is found in the olfactory neural networks, visual neural system 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 normal aging as well as other neurodegenerative diseases. There is, however, some data to 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, but more research is needed. Further investigation is also needed to disentangle the sensory and motor changes associated with AD from those associated with normal aging to harness their potential as early, non-invasive AD biomarkers.
This initiative will fill a gap area that is not being sufficiently addressed by other NIA Alzheimer’s disease initiatives and follows on the heels of a recent report from the National Academies of Sciences, Engineering, and Medicine (NASEM) recommending methodological improvements to clinical trials aimed at preventing cognitive decline and dementia. These recommendations include initiating interventions at younger ages and allowing for longer follow-up periods. Identifying non-invasive biomarkers of preclinical AD would be crucial to improving AD prevention trials.
This FOA encourages applications investigating how functional changes in sensory systems (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. Given that assessments of multiple sensory and/or motor modalities may improve the diagnostic accuracy of preclinical AD, studies proposing to investigate a single sensory or motor modality will not be supported. 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. Applications proposing clinical trials will not be accepted under this FOA.
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
- Understanding 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 at the circuit level how sensory and/or motor changes may impact preclinical AD
- Understanding 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 distinguishing sensory and/or motor changes associated with early AD from those associated with normal aging
Deadlines: standard dates apply
Filed Under: Funding Opportunities