Cognitive reserve hypothesis: Pittsburgh Compound B and fluorodeoxyglucose positron emission tomography in relation to education in mild Alzheimer's disease

Objective The reduced risk for Alzheimer's disease (AD) in high‐educated individuals has been proposed to reflect brain cognitive reserve, which would provide more efficient compensatory mechanisms against the underlying pathology, and thus delayed clinical expression. Our aim was to find possible differences in brain amyloid ligand 11C‐labeled Pittsburgh Compound B ([11C]PIB) uptake and glucose metabolism in high‐ and low‐educated patients with mild AD. Methods Twelve high‐educated and 13 low‐educated patients with the same degree of cognitive deterioration were studied with PET using [11C]PIB and 18F‐fluorodeoxyglucose as ligands. The between‐group differences were analyzed with voxel‐based statistical method, and quantitative data were obtained with automated region‐of‐interest analysis. Results High‐educated patients showed increased [11C]PIB uptake in the lateral frontal cortex compared with low‐educated patients. Moreover, high‐educated patients had significantly lower glucose metabolic rate in the temporoparietal cortical regions compared with low‐educated patients. Interpretation Our results suggesting more advanced pathological and functional brain changes in high‐educated patients with mild AD are in accordance with the brain cognitive reserve hypothesis and point out the importance of development of reliable markers of underlying AD pathology for early AD diagnostics. Ann Neurol 2007