Cognitive reserve associated with FDG-PET in preclinical Alzheimer disease

Abstract

Objective: To examine the effect of education (a surrogate measure of cognitive reserve) on FDG-PET brain metabolism in elderly cognitively healthy (HC) subjects with preclinical Alzheimer disease (AD).

Methods: Fifty-two HC subjects (mean age 75 years) with FDG-PET and CSF measurement of Aβ1-42 were included from the prospective Alzheimer's Disease Neuroimaging Initiative biomarker study. HC subjects received a research classification of preclinical AD if CSF Aβ1-42 was <192 pg/mL (Aβ1-42 [+]) vs HC with normal Aβ (Aβ1-42 [-]). In regression analyses, we tested the interaction effect between education and CSF Aβ1-42 status (Aβ1-42 [+] vs Aβ1-42 [-]) on FDG-PET metabolism in regions of interest (ROIs) (posterior cingulate, angular gyrus, inferior/middle temporal gyrus) and the whole brain (voxel-based).

Results: An interaction between education and CSF Aβ1-42 status was observed for FDG-PET in the posterior cingulate (p < 0.001) and angular gyrus ROIs (p = 0.03), but was not significant for the inferior/middle temporal gyrus ROI (p = 0.06), controlled for age, sex, and global cognitive ability (Alzheimer's Disease Assessment Scale-cognitive subscale). The interaction effect was such that higher education was associated with lower FDG-PET in the Aβ1-42 (+) group, but with higher FDG-PET in the Aβ1-42 (-) group. Voxel-based analysis showed that this interaction effect was primarily restricted to temporo-parietal and ventral prefrontal brain areas.

Conclusions: Higher education was associated with lower FDG-PET in preclinical AD (Aβ1-42 [+]), suggesting that cognitive reserve had a compensatory function to sustain cognitive ability in presence of early AD pathology that alters FDG-PET metabolism.

Figure 1. Scatterplot of the interaction between education and CSF Aβ_1-42 group for predicting FDG-PET

The number of years of education is plotted against FDG-PET for the regions of interest (ROIs) of posterior cingulate gyrus (A) and angular gyrus (B). Regression lines are plotted for groups including CSF Aβ_1-42 (−) indicated by black circles and CSF Aβ_1-42 (+) indicated by red triangles.

Figure 2. Voxel-wise assessment of the interaction effect education × CSF Aβ_1-42 status for predicting FDG-PET

The t statistics projected onto the surface (A) and the effect sizes projected onto axial slices (B) are displayed. In A, red shows those brain regions with significant interaction effects (false discovery rate corrected at the cluster level at p = 0.05). The interaction effects were all in the same direction as reported for the region of interest (ROI) analysis, i.e., higher number of years of education was associated with lower FDG-PET in Aβ_1-42 (+) subjects, but the reverse was true for Aβ_1-42 (−) subjects. There were no significant interaction effects in the opposite direction. In B, colors ranging between green/yellow and red indicate the size of the interaction effects that were in the same direction as reported for the ROI analysis.