Magnetic resonance imaging improves cerebrospinal fluid biomarkers in the early detection of Alzheimer's disease

Abstract

Little is known of combined utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers for prediction of Alzheimer's disease (AD) and longitudinal data is scarce. We examined these biomarkers at baseline and longitudinally in incipient AD. Forty-five subjects [21 controls (NL-NL), 16 stable MCI (MCI-MCI), 8 MCI who declined to AD (MCI-AD)] received MRI and lumbar puncture at baseline and after 2 years. CSF measures included total and phosphorylated tau (T-tau, P-tau(231)), amyloid-beta (Abeta(42)/Abeta(40)) and isoprostane. Voxel-based morphometry identified gray matter concentration (GMC) differences best distinguishing study groups and individual GMC values were calculated. Rate of medial temporal lobe (MTL) atrophy was examined using regional boundary shift (rBS) method. At baseline, for MRI, MCI-AD showed reduced GMC-MTL, and for CSF higher CSF T-tau, P-tau(231), IP and lower Abeta(42)/Abeta(40) as compared with MCI-MCI or NL-NL. Longitudinally, rBS-MTL atrophy was higher in MCI-AD than in either MCI-MCI or NL-NL, particularly in the left hemisphere. CSF data showed longitudinally greater increases of isoprostane in MCI-AD as compared with NL-NL. Combining baseline CSF-P-tau(231) and GMC-MTL significantly increased overall prediction of AD from 74% to 84% (p(step)<0.05). These results provide support for including multiple modalities of biomarkers in the identification of memory clinic patients at increased risk for dementia.

Fig. 1

Placement of right (white box) and left (black box) MTL ROIs on sinc interpolated, coronal T₁ MRI image cut to “pathological” angle (offset shows location of the ROI on one of the posterior slices).

Fig. 2

Voxel-based morphometry results: clusters with significantly different GMC in MCI-MCI subjects vs. MCI-AD subjects (A) and NL-NL subjects vs. MCI-AD subjects (B) at baseline and at follow-up.

Fig. 3

rBS atrophy rates in the left (A) and right (B) MTL region for the three diagnostic outcome groups. The bars represent mean value ± SEM. One star indicates p < 0.05, two stars: p < 0.001.