Dataset Information

Machine Learning and Novel Biomarkers for the Diagnosis of Alzheimer's Disease.

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.

SUBMITTER: Chang CH

PROVIDER: S-EPMC7963160 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEarly and accurate diagnosis of Alzheimer's disease (AD) is essential for disease management and therapeutic choices that can delay disease progression. Machine learning (ML) approaches have been extensively used in attempts to develop algorithms for reliable early diagnosis of AD, although clinical usefulness, interpretability, and generalizability of the classifiers across datasets and MRI protocols remain limited.MethodsWe report a multi-diagnostic and generalizable approach for mild cognitive impairment (MCI) and AD diagnosis using structural MRI and ML. Classifiers were trained and tested using subjects from the AD Neuroimaging Initiative (ADNI) database (n = 570) and the Open Access Series of Imaging Studies (OASIS) project database (n = 531). Several classifiers are compared and combined using voting for a decision. Additionally, we report tests of generalizability across datasets and protocols (IR-SPGR and MPRAGE), the impact of using graph theory measures on diagnostic classification performance, the relative importance of different brain regions on classification for better interpretability, and an evaluation of the potential for clinical applicability of the classifier.ResultsOur "healthy controls (HC) vs. AD" classifier trained and tested on the combination of ADNI and OASIS datasets obtained a balanced accuracy (BAC) of 90.6% and a Matthew's correlation coefficient (MCC) of 0.811. Our "HC vs. MCI vs. AD" classifier trained and tested on the ADNI dataset obtained a 62.1% BAC (33.3% being the by-chance cut-off) and 0.438 MCC. Hippocampal features were the strongest contributors to the classification decisions (approx. 25-45%), followed by temporal (approx. 13%), cingulate, and frontal regions (approx. 8-13% each), which is consistent with our current understanding of AD and its progression. Classifiers generalized well across both datasets and protocols. Finally, using graph theory measures did not improve classification performance.ConclusionsIn sum, we present a diagnostic tool for MCI and AD trained using baseline scans and a follow-up diagnosis regardless of progression, which is multi-diagnostic, generalizable across independent data sources and acquisition protocols, and with transparently reported performance. Rated as potentially clinically applicable, our tool may be clinically useful to inform diagnostic decisions in dementia, if successful in real-world prospective clinical trials.

Project description:Despite growing evidence of aberrant neuronal complexity in Alzheimer's disease (AD), it remains unclear how this variation arises. Neural oscillations reportedly comprise different functions depending on their own properties. Therefore, in this study, we investigated details of the complexity of neural oscillations by decomposing the oscillations into frequency, amplitude, and phase for AD patients. We applied resting-state magnetoencephalography (MEG) to 17 AD patients and 21 healthy control subjects. We first decomposed the source time series of the MEG signal into five intrinsic mode functions using ensemble empirical mode decomposition. We then analyzed the temporal complexities of these time series using multiscale entropy. Results demonstrated that AD patients had lower complexity on short time scales and higher complexity on long time scales in the alpha band in temporal regions of the brain. We evaluated the alpha band complexity further by decomposing it into amplitude and phase using Hilbert spectral analysis. Consequently, we found lower amplitude complexity and higher phase complexity in AD patients. Correlation analyses between spectral complexity and decomposed complexities revealed scale-dependency. Specifically, amplitude complexity was positively correlated with spectral complexity on short time scales, whereas phase complexity was positively correlated with spectral complexity on long time scales. Regarding the relevance of cognitive function to the complexity measures, the phase complexity on the long time scale was found to be correlated significantly with the Mini-Mental State Examination score. Additionally, we examined the diagnostic utility of the complexity characteristics using machine learning (ML) methods. We prepared a feature pool using multiple sparse autoencoders (SAEs), chose some discriminating features, and applied them to a support vector machine (SVM). Compared to the simple SVM and the SVM after feature selection (FS + SVM), the SVM with multiple SAEs (SAE + FS + SVM) had improved diagnostic accuracy. Through this study, we 1) advanced the understanding of neuronal complexity in AD patients using decomposed temporal complexity analysis and 2) demonstrated the effectiveness of combining ML methods with information about signal complexity for the diagnosis of AD.

Project description:BackgroundClinicopathological studies suggest that Alzheimer's disease (AD) pathology begins ?10-15 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset would, therefore, be invaluable for patient care and efficient clinical trial design. We utilized a targeted proteomics approach to discover novel cerebrospinal fluid (CSF) biomarkers that can augment the diagnostic and prognostic accuracy of current leading CSF biomarkers (A?42, tau, p-tau181).Methods and findingsUsing a multiplexed Luminex platform, 190 analytes were measured in 333 CSF samples from cognitively normal (Clinical Dementia Rating [CDR] 0), very mildly demented (CDR 0.5), and mildly demented (CDR 1) individuals. Mean levels of 37 analytes (12 after Bonferroni correction) were found to differ between CDR 0 and CDR>0 groups. Receiver-operating characteristic curve analyses revealed that small combinations of a subset of these markers (cystatin C, VEGF, TRAIL-R3, PAI-1, PP, NT-proBNP, MMP-10, MIF, GRO-?, fibrinogen, FAS, eotaxin-3) enhanced the ability of the best-performing established CSF biomarker, the tau/A?42 ratio, to discriminate CDR>0 from CDR 0 individuals. Multiple machine learning algorithms likewise showed that the novel biomarker panels improved the diagnostic performance of the current leading biomarkers. Importantly, most of the markers that best discriminated CDR 0 from CDR>0 individuals in the more targeted ROC analyses were also identified as top predictors in the machine learning models, reconfirming their potential as biomarkers for early-stage AD. Cox proportional hazards models demonstrated that an optimal panel of markers for predicting risk of developing cognitive impairment (CDR 0 to CDR>0 conversion) consisted of calbindin, A?42, and age.Conclusions/significanceUsing a targeted proteomic screen, we identified novel candidate biomarkers that complement the best current CSF biomarkers for distinguishing very mildly/mildly demented from cognitively normal individuals. Additionally, we identified a novel biomarker (calbindin) with significant prognostic potential.

Dataset Information

Machine Learning and Novel Biomarkers for the Diagnosis of Alzheimer's Disease.

Background

Methods

Methods

Results

Conclusions

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