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 Abeta1-42 were included from the prospective Alzheimer's Disease Neuroimaging Initiative biomarker study. HC subjects received a research classification of preclinical AD if CSF Abeta1-42 was <192 pg/mL (Abeta1-42 [+]) vs HC with normal Abeta (Abeta1-42 [-]). In regression analyses, we tested the interaction effect between education and CSF Abeta1-42 status (Abeta1-42 [+] vs Abeta1-42 [-]) 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 Abeta1-42 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 Abeta1-42 (+) group, but with higher FDG-PET in the Abeta1-42 (-) 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 (Abeta1-42 [+]), suggesting that cognitive reserve had a compensatory function to sustain cognitive ability in presence of early AD pathology that alters FDG-PET metabolism