MRI and CSF biomarkers in normal, MCI, and AD subjects: diagnostic discrimination and cognitive correlations

Abstract

Objective: To assess the correlations of both MRI and CSF biomarkers with clinical diagnosis and with cognitive performance in cognitively normal (CN) subjects and patients with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD).

Methods: This is a cross-sectional study with data from the Alzheimer's Disease Neuroimaging Initiative, which consists of CN subjects, subjects with aMCI, and subjects with AD with both CSF and MRI. Baseline CSF (t-tau, Abeta(1-42), and p-tau(181P)) and MRI scans were obtained in 399 subjects (109 CN, 192 aMCI, 98 AD). Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject.

Results: We found no significant correlation between CSF biomarkers and cognitive scores in any of the 3 clinical groups individually. Conversely, STAND scores correlated with both Clinical Dementia Rating-sum of boxes and Mini-Mental State Examination in aMCI and AD (p < or = 0.01). While STAND and all CSF biomarkers were predictors of clinical group membership (CN, aMCI, or AD) univariately (p < 0.001), STAND was more predictive than CSF both univariately and in combined models.

Conclusions: CSF and MRI biomarkers independently contribute to intergroup diagnostic discrimination and the combination of CSF and MRI provides better prediction than either source of data alone. However, MRI provides greater power to effect cross-sectional groupwise discrimination and better correlation with general cognition and functional status cross-sectionally. We therefore conclude that although MRI and CSF provide complementary information, MRI reflects clinically defined disease stage better than the CSF biomarkers tested.

Figure Box plots of MRI and CSF biomarker distributions by group (top row) and relationship between Structural Abnormality Index (STAND) scores and log(t-tau/Aβ_1-42) by group (bottom row) AD = Alzheimer disease; aMCI = amnestic mild cognitive impairment; CN = cognitively normal.