The Effect of Age Correction on Multivariate Classification in Alzheimer’s Disease, with a Focus on the Characteristics of Incorrectly and Correctly Classified Subjects

TY - JOUR

T1 - The Effect of Age Correction on Multivariate Classification in Alzheimer’s Disease, with a Focus on the Characteristics of Incorrectly and Correctly Classified Subjects

AU - Falahati, Farshad

AU - Ferreira, Daniel

AU - Soininen, Hilkka

AU - Mecocci, Patrizia

AU - Vellas, Bruno

AU - Tsolaki, Magda

AU - Kłoszewska, Iwona

AU - Lovestone, Simon

AU - Eriksdotter, Maria

AU - Wahlund, Lars Olof

AU - Simmons, Andrew

AU - Westman, Eric

PY - 2016/3/1

Y1 - 2016/3/1

N2 - The similarity of atrophy patterns in Alzheimer’s disease (AD) and in normal aging suggests age as a confounding factor in multivariate models that use structural magnetic resonance imaging (MRI) data. To study the effect and compare different age correction approaches on AD diagnosis and prediction of mild cognitive impairment (MCI) progression as well as investigate the characteristics of correctly and incorrectly classified subjects. Data from two multi-center cohorts were included in the study [AD = 297, MCI = 445, controls (CTL) = 340]. 34 cortical thickness and 21 subcortical volumetric measures were extracted from MRI. The age correction approaches involved: using age as a covariate to MRI-derived measures and linear detrending of age-related changes based on CTL measures. Orthogonal projections to latent structures was used to discriminate between AD and CTL subjects, and to predict MCI progression to AD, up to 36-months follow-up. Both age correction approaches improved models’ quality in terms of goodness of fit and goodness of prediction, as well as classification and prediction accuracies. The observed age associations in classification and prediction results were effectively eliminated after age correction. A detailed analysis of correctly and incorrectly classified subjects highlighted age associations in other factors: ApoE genotype, global cognitive impairment and gender. The two methods for age correction gave similar results and show that age can partially masks the influence of other aspects such as cognitive impairment, ApoE-e4 genotype and gender. Age-related brain atrophy may have a more important association with these factors than previously believed.

AB - The similarity of atrophy patterns in Alzheimer’s disease (AD) and in normal aging suggests age as a confounding factor in multivariate models that use structural magnetic resonance imaging (MRI) data. To study the effect and compare different age correction approaches on AD diagnosis and prediction of mild cognitive impairment (MCI) progression as well as investigate the characteristics of correctly and incorrectly classified subjects. Data from two multi-center cohorts were included in the study [AD = 297, MCI = 445, controls (CTL) = 340]. 34 cortical thickness and 21 subcortical volumetric measures were extracted from MRI. The age correction approaches involved: using age as a covariate to MRI-derived measures and linear detrending of age-related changes based on CTL measures. Orthogonal projections to latent structures was used to discriminate between AD and CTL subjects, and to predict MCI progression to AD, up to 36-months follow-up. Both age correction approaches improved models’ quality in terms of goodness of fit and goodness of prediction, as well as classification and prediction accuracies. The observed age associations in classification and prediction results were effectively eliminated after age correction. A detailed analysis of correctly and incorrectly classified subjects highlighted age associations in other factors: ApoE genotype, global cognitive impairment and gender. The two methods for age correction gave similar results and show that age can partially masks the influence of other aspects such as cognitive impairment, ApoE-e4 genotype and gender. Age-related brain atrophy may have a more important association with these factors than previously believed.

KW - Age correction

KW - Alzheimer’s disease

KW - Diagnostic misclassification

KW - Early diagnosis

KW - Mild cognitive impairment

KW - MRI

KW - OPLS

UR - http://www.scopus.com/inward/record.url?scp=84958171046&partnerID=8YFLogxK

U2 - 10.1007/s10548-015-0455-1

DO - 10.1007/s10548-015-0455-1

M3 - Article

AN - SCOPUS:84958171046

SN - 0896-0267

VL - 29

SP - 296

EP - 307

JO - Brain topography

JF - Brain topography

IS - 2

ER -