Cognitive reserve associated with FDG-PET in preclinical Alzheimer disease

Objective: To examine the effect of education (a surrogate measure of cognitive reserve) on FDG-PET brain metaolism 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 A beta(1-42) were included from the prospective Alzheimer's Disease Neuroimaging Initiative biomarker study. HC subjects received a research classification of preclinical AD if CSF A beta(1-42) was <192 pg/mL (A beta(1-42) [1]) vs HC with normal A beta (A beta(1-42) [-]). In regression analyses, we tested the interaction effect between education and CSF A beta(1-42) status (A beta(1-42) [+] vs A beta(1-42) [-]) 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 A beta(1-42) 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 A beta ility (Alzheimer's Disease Assessment Scale-cognitive subscale). The interaction effect was such that higher education was associated with lower FDG-PET in the A beta(1-42) (+) group, but with higher FDG-PET in the A beta(1-42) (-) 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 (A beta(1-42) [+]), suggesting that cognitive reserve had a compensatory function to sustain cognitive ability in presence of early AD pathology that alters FDG-PET metabolism. Neurology (R) 2013;80:1194-1201