GABAA Receptors in the Mongolian Gerbil: a PET Study Using [18F]Flumazenil to Determine Receptor Binding in Young and Old Animals

Kessler, Mariella; Mamach, Martin; Beutelmann, Rainer; Lukacevic, Mario; Eilert, Silvia; Bascuñana, Pablo; Fasel, A; Bengel, Frank M.; Roß, Tobias L.; Klump, Georg M.; Berding, Georg

doi:10.1007/s11307-019-01371-0

Cited by 13 publications

(7 citation statements)

References 70 publications

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“…Indeed, a reduction in PV immunoreactivity seems to be dominated by the factor age rather than by hearing loss. This is in line with results from other studies, reporting decreased inhibitory properties in the aged auditory cortex independent of hearing status (Kessler et al, 2019;Ueno et al, 2018) and a reduction in PV + neurons in other cortical areas, like somatosensory or motor (Miettinen et al, 1993).…”

Section: Reduction Of Pv + Interneurons Is Present In Aged Animals Wisupporting

confidence: 93%

Aging But Not Age-Related Hearing Loss Dominates the Decrease of Parvalbumin Immunoreactivity in the Primary Auditory Cortex of Mice

Rogalla

Hildebrandt

2020

eNeuro

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Section: Reduction Of Pv + Interneurons Is Present In Aged Animals Wisupporting

confidence: 93%

Aging But Not Age-Related Hearing Loss Dominates the Decrease of Parvalbumin Immunoreactivity in the Primary Auditory Cortex of Mice

Rogalla

Hildebrandt

2020

eNeuro

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“…As suggested by Wei Xu et al 29 , ARHL was related to tau in cerebrospinal fluid (CSF) using MRI, which supported our research. Similarly, one research adopts the distinct 18 F-florbetapir in PET among the elderly but discovers that ARHL is not related to β-amyloid, but the cause of such discrepancy remains unknown 30 .…”

Section: Discussionmentioning

confidence: 99%

Worsening hearing was associated with higher β-amyloid and tau burden in age-related hearing loss

Zheng

Yan

Hao

et al. 2022

Sci Rep

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Age-related hearing loss (ARHL) represents the frequently occurring disability that affects the elderly worldwide. The recent evidence has calculated ARHL to be most potential risk factor to predict dementia. β-amyloid plaques and tau accumulation in brain are hallmarks pathologic feature of Alzheimer’s disease (AD), which is a leading cause resulting in dementia. However, the potential mechanistic associations between ARHL and dementia remains unknown. We performed the present cross-sectional cohort study by enrolling 72 patients from research on hearing as well as the pathologic hallmarks of AD in brain. The exposure of hearing was measured by either word recognition score or mean pure-tone of the superior ear. The brain β-amyloid and tau standardized uptake value ratio (SUVR) were measured by positron emission tomography (PET). The covariates included gender, age, cardiovascular disease, education and hearing aid use. To analyze the association between hearing and β-amyloid/tau, linear regression was used and adjusted for potentially confounding covariates. Our data showed that the mean age was 67.1 ± 2.9 years. After adjusted for all the covariates, SUVR of β-amyloid showed an increase of 0.028 [95% confidence interval (CI) 0.004–0.061; P = 0.026], while that of tau exhibited an increase of 0.026 (95% CI 0.003–0.056; P = 0.033) per mean pure-tone increase by 10 dB (worsening). Likewise, per mean word-recognition score increase by 10%, the SUVR of β-amyloid showed an increase of 0.060 (95% CI 0.008–0.113; P = 0.023), while that of tau exhibited an increase of 0.059 (95% CI 0.009–0.111; P = 0.031). Taken together, our data demonstrates that hearing worsening was related to the increased burdens of β-amyloid as well as tau detected by PET, which were the AD pathological markers.

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“…SRTM is another example of a kinetic model that is implemented with basis functions for computational efficiency [25]. SRTM is often evaluated against other candidate models for characterization of novel tracers usingmodel comparison metrics [26][27][28][29]. Our findings suggest that the number of parameters stipulated for SRTM during model comparison may require a correction based on the number of basis functions used.…”

Section: B Success Of P Eff5%mentioning

confidence: 98%

Model Comparison Metrics Require Adaptive Correction if Parameters Are Discretized: Proof-of-Concept Applied to Transient Signals in Dynamic PET

Liu

Morris

2020

IEEE Trans. Med. Imaging

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Linear parametric neurotransmitter PET (lp-ntPET) is a novel kinetic model that estimates the temporal characteristics of a transient neurotransmitter component in PET data. To preserve computational simplicity in estimation, the parameters of the nonlinear term that describe this transient signal are discretized, and only a limited set of values for each parameter are allowed. Thus, linear estimation can be performed. Linear estimation is implemented using predefined basis functions that incorporate the discretized parameters. The implementation of the model using discretized parameters poses unique challenges for significance testing. Significance testing employs model comparison metrics to determine the significance of the improvement of the fit accomplished by including a basis function, i.e. it determines the presence of a transient signal in the PET data. A false positive occurs when the bases overfit data that do not contain a transient component. The number of parameters in a model, p, is necessary to determine the degrees of freedom in the model. In turn, p is crucial for the calculation of model selection metrics and controlling the false positive rate (FPR). In this work, we first explore the effect of parameter discretization on FPR by fitting simulated null data with varying numbers of bases. We demonstrate the dependence of FPR on number of bases. Then, we propose a correction to the number of parameters in the model, p eff , which adapts to the number of bases used. Implementing model selection with p eff maintains a stable FPR independent of number of bases.

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GABAA Receptors in the Mongolian Gerbil: a PET Study Using [18F]Flumazenil to Determine Receptor Binding in Young and Old Animals

Cited by 13 publications

References 70 publications

Aging But Not Age-Related Hearing Loss Dominates the Decrease of Parvalbumin Immunoreactivity in the Primary Auditory Cortex of Mice

Aging But Not Age-Related Hearing Loss Dominates the Decrease of Parvalbumin Immunoreactivity in the Primary Auditory Cortex of Mice

Worsening hearing was associated with higher β-amyloid and tau burden in age-related hearing loss

Model Comparison Metrics Require Adaptive Correction if Parameters Are Discretized: Proof-of-Concept Applied to Transient Signals in Dynamic PET

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