scholarly journals Early functional and cognitive declines measured by auditory evoked cortical potentials in Alzheimer's disease mice

2021 ◽  
Author(s):  
Ling Mei ◽  
Li-Men Liu ◽  
Kaitian Chen ◽  
Hong-Bo Zhao

Alzheimer's disease (AD) is characterized with a progressive loss of memory and cognitive decline. Early detection of AD is critical for prevention and intervention of this common neurodegenerative disease. Previous studies demonstrated that auditory dysfunction could occur at the early stage of AD. Auditory evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex but also cognitive activity in the brain. In this study, we recorded AECP in AD mice. AECP in mice usually possessed 3 waveforms. The early sensory P1 and P2 peaks were clearly visible in 1 month old mice. However, the later cognitive P3 peak was not well-developed until the age of 3 months old. In APP/PS1 AD mice, P1 and P2 were reduced at young ages (<6 months old), prior to occurrence of AD phenotypes. Different from normal aging, the cognitive peak of P3 in AD mice was diminished invisible after 4 months old. The latencies of peak N1, P2, and N2 in AD mice before 3 months were shorter than those in WT mice. Consistent with AECP changes, expression of amyloid precursor protein (APP) was visible in the AD mouse auditory cortex at 2 months old. These data indicate that AECP has significant changes in young AD mice and can serve as an early, non-invasive, objective biomarker in AD and AD-related dementia detection and diagnosis.

2021 ◽  
Vol 13 ◽  
Author(s):  
Ling Mei ◽  
Li-Man Liu ◽  
Kaitian Chen ◽  
Hong-Bo Zhao

Alzheimer’s disease (AD) is characterized by a progressive loss of memory and cognitive decline. However, the assessment of AD-associated functional and cognitive changes is still a big challenge. Auditory-evoked cortical potential (AECP) is an event-related potential reflecting not only neural activation in the auditory cortex (AC) but also cognitive activity in the brain. In this study, we used the subdermal needle electrodes with the same electrode setting as the auditory brainstem response (ABR) recording and recorded AECP in normal aging CBA/CaJ mice and APP/PS1 AD mice. AECP in mice usually appeared as three positive peaks, i.e., P1, P2, and P3, and three corresponding negative peaks, i.e., N1, N2, and N3. In normal aging CBA mice, the early sensory peaks P1, N1, and P2 were reduced as age increased, whereas the later cognitive peaks N2, P3, and N3 were increased or had no changes with aging. Moreover, the latency of the P1 peak was increased as age increased, although the latencies of later peaks had a significant reduction with aging. In AD mice, peak P1 was significantly reduced in comparison with wild-type (WT) littermates at young ages, proceeding AD phenotype presentation. In particular, the later cognitive peak P3 was diminished after 3 months old, different from the normal aging effect. However, the latencies of AECP peaks in AD mice generally had no significant delay or changes with aging. Finally, consistent with AECP changes, the accumulation of amyloid precursor protein (APP) at the AC was visible in AD mice as early as 2 months old. These data suggest that AECP could serve as an early, non-invasive, and objective biomarker for detecting AD and AD-related dementia (ADRD).


Author(s):  
Jingyan Qiu ◽  
Linjian Li ◽  
Yida Liu ◽  
Yingjun Ou ◽  
Yubei Lin

Alzheimer’s disease (AD) is one of the most common forms of dementia. The early stage of the disease is defined as Mild Cognitive Impairment (MCI). Recent research results have shown the prospect of combining Magnetic Resonance Imaging (MRI) scanning of the brain and deep learning to diagnose AD. However, the CNN deep learning model requires a large scale of samples for training. Transfer learning is the key to enable a model with high accuracy by using limited data for training. In this paper, DenseNet and Inception V4, which were pre-trained on the ImageNet dataset to obtain initialization values of weights, are, respectively, used for the graphic classification task. The ensemble method is employed to enhance the effectiveness and efficiency of the classification models and the result of different models are eventually processed through probability-based fusion. Our experiments were completely conducted on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) public dataset. Only the ternary classification is made due to a higher demand for medical detection and diagnosis. The accuracies of AD/MCI/Normal Control (NC) of different models are estimated in this paper. The results of the experiments showed that the accuracies of the method achieved a maximum of 92.65%, which is a remarkable outcome compared with the accuracies of the state-of-the-art methods.


2021 ◽  
Vol 3 (1) ◽  
pp. 12-18
Author(s):  
Shyamasri Biswas ◽  

The emergence of biomarkers in biologic fluids is considered an important milestone in the field of Alzheimer’s disease (AD) research. Biomarkers are widely considered critically important for the diagnosis and therapeutic intervention of the disease. It is believed that an early diagnosis of AD at a presymptomatic stage could provide the key for a successful intervention and treatment of AD. It is due to the reason that preventative and therapeutic strategies that are known to be AD stage-dependent can have a better chance of clinical success at a very early stage of the disease when critical neurons are not lost. To this end, current clinical trials are extensively being employed by taking advantage of different diagnostic biomarkers. While there has been notable progress in biomarkers for AD, the current research emphasis has been on exploring non-invasive biomarkers due to the advantages of cost-effectiveness, rapid diagnosis and significantly less medical procedural complexities that make these biomarkers potential game changer in AD diagnostics. Here, we present a bird eye view on the subject and discuss the progress made in important non-invasive biomarkers for AD.


2020 ◽  
Vol 9 (6) ◽  
pp. 1673 ◽  
Author(s):  
Maria Paraskevaidi ◽  
David Allsop ◽  
Salman Karim ◽  
Francis L. Martin ◽  
StJohn Crean

Studies in the field of Alzheimer’s disease (AD) have shown the emergence of biomarkers in biologic fluids that hold great promise for the diagnosis of the disease. A diagnosis of AD at a presymptomatic or early stage may be the key for a successful treatment, with clinical trials currently investigating this. It is anticipated that preventative and therapeutic strategies may be stage-dependent, which means that they have a better chance of success at a very early stage—before critical neurons are lost. Several studies have been investigating the use of cerebrospinal fluid (CSF) and blood as clinical samples for the detection of AD with a number of established core markers, such as amyloid beta (Aβ), total tau (T-tau) and phosphorylated tau (P-tau), being at the center of clinical research interest. The use of oral samples—including saliva and buccal mucosal cells—falls under one of the least-investigated areas in AD diagnosis. Such samples have great potential to provide a completely non-invasive alternative to current CSF and blood sampling procedures. The present work is a thorough review of the results and analytical approaches, including proteomics, metabolomics, spectroscopy and microbiome analyses that have been used for the study and detection of AD using salivary samples and buccal cells. With a few exceptions, most of the studies utilizing oral samples were performed in small cohorts, which in combination with the existence of contradictory results render it difficult to come to a definitive conclusion on the value of oral markers. Proteins such as Aβ, T-tau and P-tau, as well as small metabolites, were detected in saliva and have shown some potential as future AD diagnostics. Future large-cohort studies and standardization of sample preparation and (pre-)analytical factors are necessary to determine the use of these non-invasive samples as a diagnostic tool for AD.


2014 ◽  
Vol 10 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Kirsten L. Viola ◽  
James Sbarboro ◽  
Ruchi Sureka ◽  
Mrinmoy De ◽  
Maíra A. Bicca ◽  
...  

2010 ◽  
Vol 15 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Sridhar Krishnamurti

Alzheimer's disease is neurodegenerative disorder which affects a growing number of older adults every year. With an understanding of auditory dysfunction in Alzheimer's disease, the speech-language pathologist working in the health care setting can provide better service to these individuals. The pathophysiology of the disease process in Alzheimer's disease increases the likelihood of specific types of auditory deficits as opposed to others. This article will discuss the auditory deficits in Alzheimer's disease, their implications, and the value of clinical protocols for individuals with this disease.


2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.


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