# Bioenergetic Mechanisms of Tongue Muscle Fatigue > **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $380,081 ## Abstract Abstract Alzheimer’s disease (AD) has a primary risk factor of advanced age and accounts for 50-70% of all cases of dementia worldwide. While cognitive decline is strongly associated with AD, so too are sarcopenia, fatigue, and frailty. The parent grant focuses on discovering mechanisms of oromotor sarcopenia and muscle fatigue in aging. Thus, the application of our work to AD represents a critical extension of our science. Oromotor and swallowing impairments have been identified in patients with AD at a high prevalence and high-cost relative to heath care utilization. Underlying mechanisms likely include sarcopenia and muscle fatigue, but this has not been previously explored in cranial muscles. This supplement will apply techniques and approaches in current use in our laboratory to acquiring knowledge in AD. Our global hypothesis is that AD is associated with increases in tongue muscle sarcopenia and fatigue that contribute to deficits in oromotor function and swallowing. We further hypothesize that tongue exercise can mitigate these deficits. We will gain insight into mechanisms by addressing this global hypothesis in the TgF344-AD rat model of AD and conducting physiological, morphological, bioenergetic, and behavioral assays in tongue muscles. Our tongue exercise program is modeled after those used in current clinical practice. We have 3 specific aims: Aim 1 will test the hypothesis that measures of tongue muscle sarcopenia are found in AD; Aim 2 will test the hypothesis that deglutition outcomes are negatively affected by AD and are associated with measures of sarcopenia; and Aim 3 will test the hypothesis that tongue exercise leads to improvement in measures of tongue muscle sarcopenia in a rat model of AD. Our neuromuscular paradigm is the first to evaluate these crucial issues in muscles of the tongue in a rat model of AD. The proposed research will provide a new understanding of mechanisms that underlie oromotor and swallowing deficits from a physiological perspective, the relationship of structural changes to physiological function, and the effectiveness of lingual exercise as an intervention in AD. Rehabilitation is often not provided to patients with AD due to uncertain benefit. To advance the efficacy of services, treatments must be optimized based on preclinical methods to allow rational hypotheses for clinical studies. This work is highly significant due to the large and increasing population of people with AD who will benefit from treatments optimized in pre-clinical studies to address often debilitating oromotor and deglutition impairments. In a future R01 grant application, we will propose further studies of treatment optimization for AD- related oromotor disorders. This supplement will lay the foundation for ensuring the research of the parent grant is translationally applicable not only to the general aging population, but also to special patient populations with AD or high risks for AD. ## Key facts - **NIH application ID:** 10496825 - **Project number:** 3R01DC018071-03S1 - **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON - **Principal Investigator:** NADINE P CONNOR - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $380,081 - **Award type:** 3 - **Project period:** 2019-07-15 → 2024-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10496825 ## Citation > US National Institutes of Health, RePORTER application 10496825, Bioenergetic Mechanisms of Tongue Muscle Fatigue (3R01DC018071-03S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10496825. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*