The current study explored whether education, a proxy of cognitive reserve, modifies the association between episodic memory performance and βeta-amyloid load (Aβ), a biomarker of Alzheimer’s disease, in a cohort of cognitively normal elderly adults. One hundred and four participants (mean age 73.3 years) evenly spread out in three bands of education were recruited. Participants underwent neuropsychological assessment, structural MRI as well as PET imaging to quantify Aβ load. Moderation analyses and the Johnson-Neyman technique were carried out to examine the interaction of education with Aβ load to predict episodic memory performance. Linear regressions were then performed within each group of education to better illustrate the interaction effect (all analyses were controlled for age and sex). The interaction between education and Aβ load was significant (p<0.05) for years of education, reaching a cut-off point of 13.5 years, above which the relationship between Aβ load and episodic memory was no longer significant. Similarly, significant associations were found between Aβ and episodic memory among participants with secondary (p<0.01) and pre-university education (p<0.01), but not with a university degree (p=0.253). Episodic memory performance is associated with Aβ load in cognitively normal elderly individuals, and this relationship is moderated by educational attainment.

Amyloid‐beta (Aβ) deposition is one of the main hallmarks of Alzheimer's disease. The study assessed the associations between cortical and subcortical 11C‐Pittsburgh Compound B (PiB) retention, namely, in the hippocampus, amygdala, putamen, caudate, pallidum, and thalamus, and subcortical morphology in cognitively normal individuals. We recruited 104 cognitive normal individuals who underwent extensive neuropsychological assessment, PiB–positron emission tomography (PET) scan, and 3‐T magnetic resonance imaging (MRI) acquisition of T1‐weighted images. Global, cortical, and subcortical regional PiB retention values were derived from each scan and subcortical morphology analyses were performed to investigate vertex‐wise local surface and global volumes, including the hippocampal subfields volumes. We found that subcortical regional Aβ was associated with the surface of the hippocampus, thalamus, and pallidum, with changes being due to volume and shape. Hippocampal Aβ was marginally associated with volume of the whole hippocampus as well as with the CA1 subfield, subiculum, and molecular layer. Participants showing higher subcortical Aβ also showed worse cognitive performance and smaller hippocampal volumes. In contrast, global and cortical PiB uptake did not associate with any subcortical metrics. This study shows that subcortical Aβ is associated with subcortical surface morphology in cognitively normal individuals. This study highlights the importance of quantifying subcortical regional PiB retention values in these individuals.

This study examined the additive vs synergistic contribution of beta-amyloid (Aβ) and white matter hyperintensities (WMH) across seven cognitive domains in 104 cognitively normal older adults. It also measured the extent to which age-related differences in cognition are driven by measurable brain pathology. All participants underwent neuropsychological assessment along with MRI and PiB-PET imaging for Aβ quantification. WMH severity was quantified using the ARWMC scale.Stepwise regressions, moderation and mediation modelling were performed. Our findings show that Aβ deposition single-handedly predicts poorer episodic memory performance, and that Aβ and WMH contribute additively to poorer performance in working memory and language while carrying synergistic associations with executive functions and attention. Through mediation modelling, we demonstrated that the influence of age over episodic memory, working memory, executive functions and language is fully mediated by brain pathology. This study permits to conclude that, in healthy older adults; 1) Aβ burden and WMH have synergistic associations with some cognitive domains and; 2) age-related differences in most cognitive domains are driven by brain pathology associated with dementia.