Vocal Fold Atrophy in an Alzheimer's Disease Rat Model

Advanced Alzheimer's disease (AD) is associated with impaired voice, oropharyngeal dysphagia, and aspiration pneumonia. Vocal fold atrophy is hypothesized to contribute to these changes. While vocal fold atrophy is observed in AD, advanced age is co-prevalent and a confounding variable. The apolipoprotein E4 knock-in (ApoE4-KI) rat model is commonly used to study cognitive and motor changes in AD. This study aims to compare vocal fold atrophy in adult AD rats vs. age-matched controls.

Vocal folds were visualized endoscopically in 4-month ApoE4-KI rats (n = 12) and age-matched controls (n = 8) following anesthesia. The thyroarytenoid (TA) muscle was collected for histology. Vocal fold bowing index (BI) was calculated from endoscopic still images by two blinded reviewers using digital software. Digital myofiber analysis was used to calculate TA myofiber average cross-sectional area (CSA) and minimum Feret diameter (MFD).

Mean BI was significantly higher in AD rats compared to controls (10.7 ± 2.9 vs. 6.4 ± 2.6, difference 4.3 with 95% CI 1.6-6.9, p < 0.01). TA myofiber average CSA and MFD were significantly higher in AD rats compared to controls (average CSA (μm²), 586.3 ± 76.9 vs. 435.8 ± 49.4, difference 150.5 with 95% CI 91.2-209.9, p < 0.01; MFD (μm), 23.0 ± 1.1 vs. 19.8 ± 1.3, difference 3.2 with 95% CI 2.0-4.4, p < 0.01).

Non-aged AD rats had significantly higher BI and TA myofiber size than controls. BI was strongly correlated with histologic metrics. These findings suggest that AD may lead to greater vocal fold atrophy in non-aged animals. Additional studies are needed to determine the mechanism(s) for vocal fold atrophy in this model.

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