Cortical thickness mediates the effect of β-amyloid on episodic memory

Objective: To investigate the associations among β-amyloid (Aβ), cortical thickness, and episodic memory in a cohort of cognitively normal to mildly impaired individuals at increased risk of vascular disease. Methods: In 67 subjects specifically recruited to span a continuum of cognitive function and vascular risk, we measured brain Ab deposition using [11C] Pittsburgh compound B-PET imaging and cortical thickness using MRI. Episodic memory was tested using a standardized composite score of verbal memory, and vascular risk was quantified using the Framingham Coronary Risk Profile index. Results: Increased Ab was associated with cortical thinning, notably in frontoparietal regions. This relationship was strongest in persons with high Ab deposition. Increased Ab was also associated with lower episodic memory performance. Cortical thickness was found to mediate the relationship between Ab and memory performance. While age had a marginal effect on these associations, the relationship between Ab and cortical thickness was eliminated after controlling for vascular risk except when examined in only Pittsburgh compound B-positive subjects, in whom Ab remained associated with thinner cortex in precuneus and occipital lobe. In addition, only the precuneus was found to mediate the relationship between Ab and memory after controlling for vascular risk. Conclusion: These results suggest strong links among Ab, cortical thickness, and memory. They highlight that, in individuals without dementia, vascular risk also contributes to cortical thickness and influences the relationships among Ab, cortical thickness, and memory.