Rat Model of Aerodigestive Dysfunction in Alzheimer’s Disease

Abstract

AbstractBackgroundOral nutrition and aspiration pneumonia are significant factors impacting survival in patients with Alzheimer’s disease and related dementias (ADRD). Patients with ADRD demonstrate impairments to critical aerodigestive functions, including: prolonged oral phase durations, impaired masticatory performance, and prolonged swallow apnea durations. However, the pathophysiology underlying these functional changes is poorly understood. Establishing a translational model of swallowing dysfunction in ADRD will be critical for identifying underlying mechanisms of aerodigestive dysfunction and optimizing clinical treatments.MethodsAdult male TgF344‐AD rats (n = 6) and wild type rats (WT; n = 6) underwent videofluoroscopy (60 fps) to assess swallowing kinematics at 12 months of age. Jaw movement, bolus position, and diaphragm movement (proxy for respiration) were analyzed off‐line. All rats underwent a hypoglossal nerve electrical stimulation protocol, with the protruded tongue attached via small suture to a force transducer. All rats were stimulated maximally at a range of frequencies from 1 Hz – 140 Hz.ResultsThe AD group had significantly slower mastication rates (p = .037) and prolonged swallow apnea durations (p = .017) compared to WT. The AD group produced significantly lower forces at 60 Hz (p<.001) and 80 Hz (p<.001), indicating a higher frequency of nerve stimulation was required to elicit a given force of isometric tongue muscle contraction.ConclusionThe TgF344‐AD rat demonstrates functional mastication and swallowing decline consistent with clinical findings in patients with ADRD, with concomitant alterations in tongue muscle contractile properties and can serve as a valuable tool for interrogating biological and physiological mechanisms of aerodigestive dysfunction.