A Study on Voice Measures in Patients With Alzheimer's Disease

Xiu, Noé; Vaxelaire, Béatrice; Li, Lanlan; Ling, Zhenhua; Xu, Xiang; Huang, Linming; Sun, Bo; Huang, Lin; Sock, Rudolph

doi:10.1016/j.jvoice.2022.08.010

Cited by 5 publications

(1 citation statement)

References 39 publications

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“…Because diagnosis occurs in mid stage of the disease ( Larson et al, 2004 ; Bradford et al, 2009 ; de Miranda et al, 2011 ; Emery, 2011 ; Rajan et al, 2015 ; Mantzavinos and Alexiou, 2017 ; Leuzy et al, 2018 ; Petersen, 2018 ; Ausó et al, 2020 ; Porsteinsson et al, 2021 ; van Oostveen and de Lange, 2021 ; Veitch et al, 2022 ), when laryngeal dysfunction has already progressed ( Miguel and Irma, 2020 ; Mahon and Lachman, 2022 ; Xiu et al, 2022 ; Hajjar et al, 2023 ), quantifying the prodrome and early stages is challenging in humans ( Jack et al, 2013 ; Leuzy et al, 2018 ; Cummings, 2019 ). This creates significant gaps in knowledge that limit our understanding for early identification and treatment of AD to improve patient trajectory throughout the disease ( The Lancet Neurology, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Early ultrasonic vocalization deficits and related thyroarytenoid muscle pathology in the transgenic TgF344-AD rat model of Alzheimer’s disease

Rudisch,

Krasko,

Barnett

et al. 2024

Front. Behav. Neurosci.

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BackgroundAlzheimer’s disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and aggregation of β-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life. Because clinical diagnosis occurs in the mid-stage of the disease, characterizing the prodrome and early stages in humans is currently challenging. To overcome these challenges, we use the validated TgF344-AD (F344-Tg(Prp-APP, Prp-PS1)19/Rrrc) transgenic rat model that manifests cognitive, behavioral, and neuropathological dysfunction akin to AD in humans.ObjectivesThe overarching goal of our work is to test the central hypothesis that pathology and related behavioral deficits such as communication dysfunction in part manifest in the peripheral nervous system and corresponding target tissues already in the early stages. The primary aims of this study are to test the hypotheses that: (1) changes in ultrasonic vocalizations (USV) occur in the prodromal stage at 6 months of age and worsen at 9 months of age, (2) inflammation as well as AD-related pathology can be found in the thyroarytenoid muscle (TA) at 12 months of age (experimental endpoint tissue harvest), and to (3) demonstrate that the TgF344-AD rat model is an appropriate model for preclinical investigations of early AD-related vocal deficits.MethodsUSVs were collected from male TgF344-AD (N = 19) and wildtype (WT) Fischer-344 rats (N = 19) at 6 months (N = 38; WT: n = 19; TgF344-AD: n = 19) and 9 months of age (N = 18; WT: n = 10; TgF344-AD: n = 8) and acoustically analyzed for duration, mean power, principal frequency, low frequency, high frequency, peak frequency, and call type. RT-qPCR was used to assay peripheral inflammation and AD-related pathology via gene expressions in the TA muscle of male TgF344-AD rats (n = 6) and WT rats (n = 6) at 12 months of age.ResultsThis study revealed a significant reduction in mean power of ultrasonic calls from 6 to 9 months of age and increased peak frequency levels over time in TgF344-AD rats compared to WT controls. Additionally, significant downregulation of AD-related genes Uqcrc2, Bace2, Serpina3n, and Igf2, as well as downregulation of pro-inflammatory gene Myd88 was found in the TA muscle of TgF344-AD rats at 12 months of age.DiscussionOur findings demonstrate early and progressive vocal deficits in the TgF344-AD rat model. We further provide evidence of dysregulation of AD-pathology-related genes as well as inflammatory genes in the TA muscles of TgF344-AD rats in the early stage of the disease, confirming this rat model for early-stage investigations of voice deficits and related pathology.

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