Abstract

Background: Alzheimer’s disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis. Methods: We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD. Methods: We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD. Results: In additional to Aβ and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls. Conclusions: Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.

Highlights

  • Machine learning algorithms can be divided into supervised models where the data are labeled, unsupervised algorithms where the aim is to separate an unlabeled data into groups of related cases, and semi-supervised algorithms including both labeled and unlabeled data [30]

  • A machine learning algorithm is a procedure for selecting the best model from a set of alternatives that fit a set of observations

  • Models predicted (AUC = 0.92) Aβ+—amnestic Mild Cognitive Impairment patients who will develop Alzheimer’s disease (AD) in PharmaCog/E-Alzheimer’s Disease Neuroimaging Initiative (ADNI), where subjects were stratified according to Cerebrospinal fluid (CSF) AD markers (Aβ42 and p-Tau)

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Summary

Conclusions

Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics. Keywords: machine learning; deep learning; AI; biomarker; Alzheimer’s disease iations.

Introduction
Methods
Machine Learning Models in Alzheimer’s Disease
PET-Based Tau Biomarker with Machine Learning
Metabolites Biomarkers with Machine Learning
Outlook and Future Direction

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