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 11 C-labeled Pittsburgh Compound B ([ 11 C]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 [ 11 C]PIB and 18 F-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 [11 C]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. Neurol 2008;63:112-118 Several epidemiological studies have found a lower incidence of Alzheimer's disease (AD) in high-educated populations, suggesting that education provides protection against the disease. Ann1 This reduced risk for AD in high-educated individuals is proposed to reflect brain cognitive reserve that provides greater brain capacity to compensate for disruption caused by disease pathology, and thus delays the clinical expression of AD.2 At a particular level of AD pathology, highly educated individuals are less likely to manifest clinical symptoms of dementia as compared with less educated individuals.3 After the diagnosis of AD, higheducated individuals show more rapid progression of dementia and lower survival compared with loweducated AD patients. 4 -6 The different course of the disease between these groups has been hypothesized to reflect a more advanced AD pathology at the time of diagnosis in high-educated patients, and a rapid cognitive deterioration after the compensatory capacity becomes insufficient.The association of educational level with the severity of brain damage in AD has been evaluated in vivo with positron emission tomography (PET) and singlephoton emission computed tomography by using the brain glucose metabolism or cerebral blood flow as measures of brain functional changes.7-12 These studies have shown an inverse relation between the level of education and brain glucose metabolism or blood flow after adjusted for the dementia severity. This relation was evident especially in brain regions typically affected in AD, such as temporal and parietal cortices. The effect of education on the ...

PurposeAmyloid PET tracers have been developed for in vivo detection of brain fibrillar amyloid deposition in Alzheimer’s disease (AD). To serve as an early biomarker in AD the amyloid PET tracers need to be analysed in multicentre clinical studies.MethodsIn this study 238 [11C]Pittsburgh compound-B (PIB) datasets from five different European centres were pooled. Of these 238 datasets, 18 were excluded, leaving [11C]PIB datasets from 97 patients with clinically diagnosed AD (mean age 69 ± 8 years), 72 patients with mild cognitive impairment (MCI; mean age 67.5 ± 8 years) and 51 healthy controls (mean age 67.4 ± 6 years) available for analysis. Of the MCI patients, 64 were longitudinally followed for 28 ± 15 months. Most participants (175 out of 220) were also tested for apolipoprotein E (ApoE) genotype.Results[11C]PIB retention in the neocortical and subcortical brain regions was significantly higher in AD patients than in age-matched controls. Intermediate [11C]PIB retention was observed in MCI patients, with a bimodal distribution (64 % MCI PIB-positive and 36 % MCI PIB-negative), which was significantly different the pattern in both the AD patients and controls. Higher [11C]PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p < 0.005). Of the MCI PIB-positive patients, 67 % had converted to AD at follow-up while none of the MCI PIB-negative patients converted.ConclusionThis study demonstrated the robustness of [11C]PIB PET as a marker of neocortical fibrillar amyloid deposition in brain when assessed in a multicentre setting. MCI PIB-positive patients showed more severe memory impairment than MCI PIB-negative patients and progressed to AD at an estimated rate of 25 % per year. None of the MCI PIB-negative patients converted to AD, and thus PIB negativity had a 100 % negative predictive value for progression to AD. This supports the notion that PIB-positive scans in MCI patients are an indicator of prodromal AD.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-012-2237-2) contains supplementary material, which is available to authorized users.

The results suggest no (or only little) increase in (11)C-labeled Pittsburgh compound B ([(11)C]PIB) uptake during 2 years of Alzheimer disease progression, despite advancing brain atrophy and declining cognitive performance. Nevertheless, changes in [(11)C]PIB uptake during a longer follow-up cannot be excluded. High cortical [(11)C]PIB uptake may predict ongoing brain atrophy in cognitively normal individuals.

Aim: To compare the diagnostic accuracy of a computerized test, the CANTAB paired associate learning (PAL) to that of an established and validated noncomputerized test, the CERAD Wordlist Learning task in differentiating between normal aging, aMCI and AD in a cross-sectional design. Methods: 58 participants were assessed (19 with mild probable AD, 17 aMCI, 22 healthy controls). Results: The variables found to best discriminate between the three groups were the CANTAB PAL total errors adjusted (p < 0.0001, 81.0% of the cases correctly classified), and CERAD Wordlist Learning Delayed Recall (p < 0.0001, 77.6% of the cases correctly classified). Using both PAL total errors adjusted and Wordlist Learning Delayed Recall, 84.5% of the cases were correctly classified. Discussion: The results suggest that the CANTAB could be used for screening of AD-typical memory impairment.