Olfactory Phenotypes Differentiate Cognitively Unimpaired Seniors from Alzheimer’s Disease and Mild Cognitive Impairment: A Combined Machine Learning and Traditional Statistical Approach

2021 ◽  
pp. 1-10
Author(s):  
Jennifer Li ◽  
Andres M. Bur ◽  
Mark R. Villwock ◽  
Suraj Shankar ◽  
Gracie Palmer ◽  
...  

Background: Olfactory dysfunction (OD) is an early symptom of Alzheimer’s disease (AD). However, olfactory testing is not commonly performed to test OD in the setting of AD. Objective: This work investigates objective OD as a non-invasive biomarker for accurately classifying subjects as cognitively unimpaired (CU), mild cognitive impairment (MCI), and AD. Methods: Patients with MCI (n = 24) and AD (n = 24), and CU (n = 33) controls completed two objective tests of olfaction (Affordable, Rapid, Olfactory Measurement Array –AROMA; Sniffin’ Sticks Screening 12 Test –SST12). Demographic and subjective sinonasal and olfaction symptom information was also obtained. Analyses utilized traditional statistics and machine learning to determine olfactory variables, and combinations of variables, of importance for differentiating normal and disease states. Results: Inability to correctly identify a scent after detection was a hallmark of MCI/AD. AROMA was superior to SST12 for differentiating MCI from AD. Performance on the clove scent was significantly different between all three groups. AROMA regression modeling yielded six scents with AUC of the ROC of 0.890 (p <  0.001). Random forest model machine learning algorithms considering AROMA olfactory data successfully predicted MCI versus AD disease state. Considering only AROMA data, machine learning algorithms were 87.5%accurate (95%CI 0.4735, 0.9968). Sensitivity and specificity were 100%and 75%, respectively with ROC of 0.875. When considering AROMA and subject demographic and subjective data, the AUC of the ROC increased to 0.9375. Conclusion: OD differentiates CUs from those with MCI and AD and can accurately predict MCI versus AD. Leveraging OD data may meaningfully guide management and research decisions.

2019 ◽  
Author(s):  
Massimiliano Grassi ◽  
Nadine Rouleaux ◽  
Daniela Caldirola ◽  
David Loewenstein ◽  
Koen Schruers ◽  
...  

ABSTRACTBackgroundDespite the increasing availability in brain health related data, clinically translatable methods to predict the conversion from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) are still lacking. Although MCI typically precedes AD, only a fraction of 20-40% of MCI individuals will progress to dementia within 3 years following the initial diagnosis. As currently available and emerging therapies likely have the greatest impact when provided at the earliest disease stage, the prompt identification of subjects at high risk for conversion to full AD is of great importance in the fight against this disease. In this work, we propose a highly predictive machine learning algorithm, based only on non-invasively and easily in-the-clinic collectable predictors, to identify MCI subjects at risk for conversion to full AD.MethodsThe algorithm was developed using the open dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), employing a sample of 550 MCI subjects whose diagnostic follow-up is available for at least 3 years after the baseline assessment. A restricted set of information regarding sociodemographic and clinical characteristics, neuropsychological test scores was used as predictors and several different supervised machine learning algorithms were developed and ensembled in final algorithm. A site-independent stratified train/test split protocol was used to provide an estimate of the generalized performance of the algorithm.ResultsThe final algorithm demonstrated an AUROC of 0.88, sensitivity of 77.7%, and a specificity of 79.9% on excluded test data. The specificity of the algorithm was 40.2% for 100% sensitivity.DiscussionThe algorithm we developed achieved sound and high prognostic performance to predict AD conversion using easily clinically derived information that makes the algorithm easy to be translated into practice. This indicates beneficial application to improve recruitment in clinical trials and to more selectively prescribe new and newly emerging early interventions to high AD risk patients.


PLoS ONE ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. e0229460
Author(s):  
Sylvester Olubolu Orimaye ◽  
Karl Goodkin ◽  
Ossama Abid Riaz ◽  
Jean-Maurice Miranda Salcedo ◽  
Thabit Al-Khateeb ◽  
...  

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Sergio Grueso ◽  
Raquel Viejo-Sobera

Abstract Background An increase in lifespan in our society is a double-edged sword that entails a growing number of patients with neurocognitive disorders, Alzheimer’s disease being the most prevalent. Advances in medical imaging and computational power enable new methods for the early detection of neurocognitive disorders with the goal of preventing or reducing cognitive decline. Computer-aided image analysis and early detection of changes in cognition is a promising approach for patients with mild cognitive impairment, sometimes a prodromal stage of Alzheimer’s disease dementia. Methods We conducted a systematic review following PRISMA guidelines of studies where machine learning was applied to neuroimaging data in order to predict whether patients with mild cognitive impairment might develop Alzheimer’s disease dementia or remain stable. After removing duplicates, we screened 452 studies and selected 116 for qualitative analysis. Results Most studies used magnetic resonance image (MRI) and positron emission tomography (PET) data but also magnetoencephalography. The datasets were mainly extracted from the Alzheimer’s disease neuroimaging initiative (ADNI) database with some exceptions. Regarding the algorithms used, the most common was support vector machine with a mean accuracy of 75.4%, but convolutional neural networks achieved a higher mean accuracy of 78.5%. Studies combining MRI and PET achieved overall better classification accuracy than studies that only used one neuroimaging technique. In general, the more complex models such as those based on deep learning, combined with multimodal and multidimensional data (neuroimaging, clinical, cognitive, genetic, and behavioral) achieved the best performance. Conclusions Although the performance of the different methods still has room for improvement, the results are promising and this methodology has a great potential as a support tool for clinicians and healthcare professionals.


2021 ◽  
Author(s):  
Sergio Grueso ◽  
Raquel Viejo-Sobera

Abstract Background: Increase in life-span in our society is a double-edged sword that entails a growing number of patients with neurocognitive disorders, Alzheimer’s disease being the most prevalent. Advances in medical imaging and computational power, enable new methods for early detection of neurocognitive disorders with the goal of preventing or reducing cognitive decline. Computer-aided image analysis and early detection of changes in cognition is a promising approach for patients with mild cognitive impairment, sometimes a prodromal stage of Alzheimer’s disease.Methods: We conducted a systematic review following PRISMA guidelines of studies where Machine Learning was applied to neuroimaging data in order to predict the progression from Mild Cognitive Impairment to Alzheimer’s disease. After removing duplicates, we screened 159 studies and selected 47 for a qualitative analysis. Results: Most studies used Magnetic Resonance Image and Positron Emission Tomography data but also Magnetoencephalography. The datasets were mainly extracted from the Alzheimer’s disease Neuroimage Initiative (ADNI) database with some exceptions. Regarding the algorithms used, the most common were support vector machines, but more complex models such as Deep Learning, combined with multimodal and multidimensional data (neuroimaging, clinical, cognitive, biological, and behavioral) achieved the best performance. Conclusions: Although performance of the different models still has room for improvement, the results are promising and this methodology has a great potential as a support tool for clinicians and healthcare professionals.


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