Dataset Information

Predicting the time of conversion to MCI in the elderly: role of verbal expression and learning.

ABSTRACT:

Background

Increasing awareness that minimal or mild cognitive impairment (MCI) in the elderly may be a precursor of dementia has led to an increase in the number of people attending memory clinics. We aimed to develop a way of predicting the period of time before cognitive impairment occurs in community-dwelling elderly. The method is illustrated by the use of simple tests of different cognitive domains.

Methods

A cohort of 241 normal elderly volunteers was followed for up to 20 years with regular assessments of cognitive abilities using the Cambridge Cognitive Examination (CAMCOG); 91 participants developed MCI. We used interval-censored survival analysis statistical methods to model which baseline cognitive tests best predicted the time to convert to MCI.

Results

Out of several baseline variables, only age and CAMCOG subscores for expression and learning/memory were predictors of the time to conversion. The time to conversion was 14% shorter for each 5 years of age, 17% shorter for each point lower in the expression score, and 15% shorter for each point lower in the learning score. We present in tabular form the probability of converting to MCI over intervals between 2 and 10 years for different combinations of expression and learning scores.

Conclusion

In apparently normal elderly people, subtle measurable cognitive deficits that occur within the normal range on standard testing protocols reliably predict the time to clinically relevant cognitive impairment long before clinical symptoms are reported.

SUBMITTER: Oulhaj A

PROVIDER: S-EPMC2882176 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Publications

Predicting the time of conversion to MCI in the elderly: role of verbal expression and learning.

Oulhaj Abderrahim A Wilcock Gordon K GK Smith A David AD de Jager Celeste A CA

Neurology 20090930 18

<h4>Background</h4>Increasing awareness that minimal or mild cognitive impairment (MCI) in the elderly may be a precursor of dementia has led to an increase in the number of people attending memory clinics. We aimed to develop a way of predicting the period of time before cognitive impairment occurs in community-dwelling elderly. The method is illustrated by the use of simple tests of different cognitive domains.<h4>Methods</h4>A cohort of 241 normal elderly volunteers was followed for up to 20 ...[more]

PMID: 19794124

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Project description:BackgroundPatients with Mild Cognitive Impairment (MCI) are at high risk of progression to Alzheimer's dementia. Identifying MCI individuals with high likelihood of conversion to dementia and the associated biosignatures has recently received increasing attention in AD research. Different biosignatures for AD (neuroimaging, demographic, genetic and cognitive measures) may contain complementary information for diagnosis and prognosis of AD.MethodsWe have conducted a comprehensive study using a large number of samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to test the power of integrating various baseline data for predicting the conversion from MCI to probable AD and identifying a small subset of biosignatures for the prediction and assess the relative importance of different modalities in predicting MCI to AD conversion. We have employed sparse logistic regression with stability selection for the integration and selection of potential predictors. Our study differs from many of the other ones in three important respects: (1) we use a large cohort of MCI samples that are unbiased with respect to age or education status between case and controls (2) we integrate and test various types of baseline data available in ADNI including MRI, demographic, genetic and cognitive measures and (3) we apply sparse logistic regression with stability selection to ADNI data for robust feature selection.ResultsWe have used 319 MCI subjects from ADNI that had MRI measurements at the baseline and passed quality control, including 177 MCI Non-converters and 142 MCI Converters. Conversion was considered over the course of a 4-year follow-up period. A combination of 15 features (predictors) including those from MRI scans, APOE genotyping, and cognitive measures achieves the best prediction with an AUC score of 0.8587.ConclusionsOur results demonstrate the power of integrating various baseline data for prediction of the conversion from MCI to probable AD. Our results also demonstrate the effectiveness of stability selection for feature selection in the context of sparse logistic regression.

Project description:Mild cognitive impairment (MCI) is a transitional stage between age-related cognitive decline and Alzheimer's disease (AD). For the effective treatment of AD, it would be important to identify MCI patients at high risk for conversion to AD. In this study, we present a novel magnetic resonance imaging (MRI)-based method for predicting the MCI-to-AD conversion from one to three years before the clinical diagnosis. First, we developed a novel MRI biomarker of MCI-to-AD conversion using semi-supervised learning and then integrated it with age and cognitive measures about the subjects using a supervised learning algorithm resulting in what we call the aggregate biomarker. The novel characteristics of the methods for learning the biomarkers are as follows: 1) We used a semi-supervised learning method (low density separation) for the construction of MRI biomarker as opposed to more typical supervised methods; 2) We performed a feature selection on MRI data from AD subjects and normal controls without using data from MCI subjects via regularized logistic regression; 3) We removed the aging effects from the MRI data before the classifier training to prevent possible confounding between AD and age related atrophies; and 4) We constructed the aggregate biomarker by first learning a separate MRI biomarker and then combining it with age and cognitive measures about the MCI subjects at the baseline by applying a random forest classifier. We experimentally demonstrated the added value of these novel characteristics in predicting the MCI-to-AD conversion on data obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. With the ADNI data, the MRI biomarker achieved a 10-fold cross-validated area under the receiver operating characteristic curve (AUC) of 0.7661 in discriminating progressive MCI patients (pMCI) from stable MCI patients (sMCI). Our aggregate biomarker based on MRI data together with baseline cognitive measurements and age achieved a 10-fold cross-validated AUC score of 0.9020 in discriminating pMCI from sMCI. The results presented in this study demonstrate the potential of the suggested approach for early AD diagnosis and an important role of MRI in the MCI-to-AD conversion prediction. However, it is evident based on our results that combining MRI data with cognitive test results improved the accuracy of the MCI-to-AD conversion prediction.

Project description:BackgroundGraph theory and machine learning have been shown to be effective ways of classifying different stages of Alzheimer's disease (AD). Most previous studies have only focused on inter-subject classification with single-mode neuroimaging data. However, whether this classification can truly reflect the changes in the structure and function of the brain region in disease progression remains unverified. In the current study, we aimed to evaluate the classification framework, which combines structural Magnetic Resonance Imaging (sMRI) and resting-state functional Magnetic Resonance Imaging (rs-fMRI) metrics, to distinguish mild cognitive impairment non-converters (MCInc)/AD from MCI converters (MCIc) by using graph theory and machine learning.MethodsWith the intra-subject (MCInc vs. MCIc) and inter-subject (MCIc vs. AD) design, we employed cortical thickness features, structural brain network features, and sub-frequency (full-band, slow-4, slow-5) functional brain network features for classification. Three feature selection methods [random subset feature selection algorithm (RSFS), minimal redundancy maximal relevance (mRMR), and sparse linear regression feature selection algorithm based on stationary selection (SS-LR)] were used respectively to select discriminative features in the iterative combinations of MRI and network measures. Then support vector machine (SVM) classifier with nested cross-validation was employed for classification. We also compared the performance of multiple classifiers (Random Forest, K-nearest neighbor, Adaboost, SVM) and verified the reliability of our results by upsampling.ResultsWe found that in the classifications of MCIc vs. MCInc, and MCIc vs. AD, the proposed RSFS algorithm achieved the best accuracies (84.71, 89.80%) than the other algorithms. And the high-sensitivity brain regions found with the two classification groups were inconsistent. Specifically, in MCIc vs. MCInc, the high-sensitivity brain regions associated with both structural and functional features included frontal, temporal, caudate, entorhinal, parahippocampal, and calcarine fissure and surrounding cortex. While in MCIc vs. AD, the high-sensitivity brain regions associated only with functional features included frontal, temporal, thalamus, olfactory, and angular.ConclusionsThese results suggest that our proposed method could effectively predict the conversion of MCI to AD, and the inconsistency of specific brain regions provides a novel insight for clinical AD diagnosis.

Dataset Information

Predicting the time of conversion to MCI in the elderly: role of verbal expression and learning.

Background

Methods

Results

Conclusion

Publications

Predicting the time of conversion to MCI in the elderly: role of verbal expression and learning.

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