A machine learning-based holistic and age-dependent approach for the diagnosis within the Alzheimer's disease spectrum

2021 ◽  
Vol 429 ◽  
pp. 119015
Author(s):  
Noemi Massetti ◽  
Alberto Granzotto ◽  
Manuela Bomba ◽  
Stefano Delli Pizzi ◽  
Alessandra Mosca ◽  
...  
2020 ◽  
Author(s):  
Noemi Massetti ◽  
Alberto Granzotto ◽  
Manuela Bomba ◽  
Stefano Delli Pizzi ◽  
Alessandra Mosca ◽  
...  

Alzheimer's disease (AD) is a neurodegenerative condition driven by a multifactorial etiology. We employed a machine learning (ML) based algorithm and the wealth of information offered by the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to investigate the relative contribution of clinically relevant factors for identifying subjects affected by Mild Cognitive Impairment (MCI), a transitional status between healthy aging and dementia. Our ML-based Random Forest (RF) algorithm did not help predict clinical outcomes and the AD conversion of MCI subjects. On the other hand, non-converting (ncMCI) subjects were correctly classified and predicted. Two neuropsychological tests, the FAQ and ADAS13, were the most relevant features used for the classification and prediction of younger, under 70, ncMCI subjects. Structural MRI data combined with systemic parameters and the cardiovascular status were instead the most critical factors for the classification of over 70 ncMCI subjects. Our results support the notion that AD is not an organ-specific condition and results from pathological processes inside and outside the Central Nervous System.


2021 ◽  
pp. 1-17
Author(s):  
Noemi Massetti ◽  
Mirella Russo ◽  
Raffaella Franciotti ◽  
Davide Nardini ◽  
Giorgio Mandolini ◽  
...  

Background: Alzheimer’s disease (AD) is a neurodegenerative condition driven by multifactorial etiology. Mild cognitive impairment (MCI) is a transitional condition between healthy aging and dementia. No reliable biomarkers are available to predict the conversion from MCI to AD. Objective: To evaluate the use of machine learning (ML) on a wealth of data offered by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Alzheimer’s Disease Metabolomics Consortium (ADMC) database in the prediction of the MCI to AD conversion. Methods: We implemented an ML-based Random Forest (RF) algorithm to predict conversion from MCI to AD. Data related to the study population (587 MCI subjects) were analyzed by RF as separate or combined features and assessed for classification power. Four classes of variables were considered: neuropsychological test scores, AD-related cerebrospinal fluid (CSF) biomarkers, peripheral biomarkers, and structural magnetic resonance imaging (MRI) variables. Results: The ML-based algorithm exhibited 86% accuracy in predicting the AD conversion of MCI subjects. When assessing the features that helped the most, neuropsychological test scores, MRI data, and CSF biomarkers were the most relevant in the MCI to AD prediction. Peripheral parameters were effective when employed in association with neuropsychological test scores. Age and sex differences modulated the prediction accuracy. AD conversion was more effectively predicted in females and younger subjects. Conclusion: Our findings support the notion that AD-related neurodegenerative processes result from the concerted activity of multiple pathological mechanisms and factors that act inside and outside the brain and are dynamically affected by age and sex.


2016 ◽  
Vol 13 (5) ◽  
pp. 498-508 ◽  
Author(s):  
V. Vigneron ◽  
A. Kodewitz ◽  
A. M. Tome ◽  
S. Lelandais ◽  
E. Lang

Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1071
Author(s):  
Lucia Billeci ◽  
Asia Badolato ◽  
Lorenzo Bachi ◽  
Alessandro Tonacci

Alzheimer’s disease is notoriously the most common cause of dementia in the elderly, affecting an increasing number of people. Although widespread, its causes and progression modalities are complex and still not fully understood. Through neuroimaging techniques, such as diffusion Magnetic Resonance (MR), more sophisticated and specific studies of the disease can be performed, offering a valuable tool for both its diagnosis and early detection. However, processing large quantities of medical images is not an easy task, and researchers have turned their attention towards machine learning, a set of computer algorithms that automatically adapt their output towards the intended goal. In this paper, a systematic review of recent machine learning applications on diffusion tensor imaging studies of Alzheimer’s disease is presented, highlighting the fundamental aspects of each work and reporting their performance score. A few examined studies also include mild cognitive impairment in the classification problem, while others combine diffusion data with other sources, like structural magnetic resonance imaging (MRI) (multimodal analysis). The findings of the retrieved works suggest a promising role for machine learning in evaluating effective classification features, like fractional anisotropy, and in possibly performing on different image modalities with higher accuracy.


Author(s):  
M. Tanveer ◽  
B. Richhariya ◽  
R. U. Khan ◽  
A. H. Rashid ◽  
P. Khanna ◽  
...  

2020 ◽  
Vol 29 (5) ◽  
pp. 817-833 ◽  
Author(s):  
Masataka Kikuchi ◽  
Michiko Sekiya ◽  
Norikazu Hara ◽  
Akinori Miyashita ◽  
Ryozo Kuwano ◽  
...  

Abstract The molecular biological mechanisms of Alzheimer’s disease (AD) involve disease-associated crosstalk through many genes and include a loss of normal as well as a gain of abnormal interactions among genes. A protein domain network (PDN) is a collection of physical bindings that occur between protein domains, and the states of the PDNs in patients with AD are likely to be perturbed compared to those in normal healthy individuals. To identify PDN changes that cause neurodegeneration, we analysed the PDNs that occur among genes co-expressed in each of three brain regions at each stage of AD. Our analysis revealed that the PDNs collapsed with the progression of AD stage and identified five hub genes, including Rac1, as key players in PDN collapse. Using publicly available as well as our own gene expression data, we confirmed that the mRNA expression level of the RAC1 gene was downregulated in the entorhinal cortex (EC) of AD brains. To test the causality of these changes in neurodegeneration, we utilized Drosophila as a genetic model and found that modest knockdown of Rac1 in neurons was sufficient to cause age-dependent behavioural deficits and neurodegeneration. Finally, we identified a microRNA, hsa-miR-101-3p, as a potential regulator of RAC1 in AD brains. As the Braak neurofibrillary tangle (NFT) stage progressed, the expression levels of hsa-miR-101-3p were increased specifically in the EC. Furthermore, overexpression of hsa-miR-101-3p in the human neuronal cell line SH-SY5Y caused RAC1 downregulation. These results highlight the utility of our integrated network approach for identifying causal changes leading to neurodegeneration in AD.


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