This work builds upon previous studies that reported high sensitivity and specificity in classifying individuals with mild cognitive impairment (MCI), which is often a prodromal phase of Alzheimer's Disease (AD), via pattern classification of MRI scans. The current study integrates MRI and PET 15 O water scans from 30 participants in the Baltimore Longitudinal Study of Aging, and tests the hypothesis that joint evaluation of structure and function can yield higher classification accuracy than either alone. Classification rates of up to 100% accuracy were achieved via leave-one-out cross validation, whereas conservative estimates of generalization performance in new scans, evaluated via bagging cross-validation, yielded an area under the receiver operating characteristic (ROC) curve equal to 0.978 (97.8%), indicating excellent diagnostic accuracy. Spatial maps of regions determined to contribute the most to the classification implicated many temporal, prefrontal, orbitofrontal, and parietal regions. Detecting complex patterns of brain abnormality in early stages of cognitive impairment has pivotal importance for the detection and management of AD.
KeywordsAlzheimer's Disease; MCI; high-dimensional Pattern Classification; MRI; PET; voxel-based analysis; diagnosis of AD Amnestic mild cognitive impairment (MCI) is often a prodromal stage to Alzheimer's Disease (AD), as individuals with MCI may convert to AD at an annual rate as high as 15% . Therefore, MCI is frequently considered to be a good target for early AD diagnosis, and for therapeutic interventions. MRI and PET imaging can potentially be used as diagnostic tools that assess brain structure and function in a direct and objective way and have potential utility for diagnosis, prognosis, and evaluation of disease progression and treatment effects.Many imaging studies have found loss of grey matter (GM) and metabolic abnormalities in MCI. Most of the earlier studies were based on volumetric measurements of regions of interest (ROI's) (Chetelat et al., 2002;Convit et al., 2000;Dickerson et al., 2001;Fox et al., 1996a;Kaye et al., 1997;Killiany et al., 2000), such as the hippocampus and the entorhinal cortex, and have confirmed GM atrophy in regions that are known to be affected by AD. However, the pattern of AD pathology is complex and evolves as the disease progresses, starting mainly in the hippocampus and entorhinal cortex, and subsequently spreading throughout temporal and orbitofrontal cortex, posterior cingulate, and association cortex generally (Braak et al., 1998). Therefore, measuring volumes or average PET signals of a few structures cannot capture Voxel-based morphometry (VBM) has been proposed by a number of investigators as a more comprehensive way of measuring the spatial distribution of brain atrophy in MCI and AD, by evaluating images region by region instead of making a priori assumptions about specific ROIs. A variety of VBM-type methods exist (Ashburner and Friston, 2000;Chung et al., 2001;Davatzikos et al., 2001;Davatzikos et al., 1996...