Vascular risk and Aβ interact to reduce cortical thickness in AD vulnerable brain regions

Abstract

Objective: The objective of this study was to define whether vascular risk factors interact with β-amyloid (Aβ) in producing changes in brain structure that could underlie the increased risk of Alzheimer disease (AD).

Methods: Sixty-six cognitively normal and mildly impaired older individuals with a wide range of vascular risk factors were included in this study. The presence of Aβ was assessed using [(11)C]Pittsburgh compound B-PET imaging, and cortical thickness was measured using 3-tesla MRI. Vascular risk was measured with the Framingham Coronary Risk Profile Index.

Results: Individuals with high levels of vascular risk factors have thinner frontotemporal cortex independent of Aβ. These frontotemporal regions are also affected in individuals with Aβ deposition, but the latter show additional thinning in parietal cortices. Aβ and vascular risk were found to interact in posterior (especially in parietal) brain regions, where Aβ has its greatest effect. In this way, the negative effect of Aβ in posterior regions is increased by the presence of vascular risk.

Conclusion: Aβ and vascular risk interact to enhance cortical thinning in posterior brain regions that are particularly vulnerable to AD. These findings give insight concerning the mechanisms whereby vascular risk increases the likelihood of developing AD and supports the therapeutic intervention of controlling vascular risk for the prevention of AD.

Figure 1. Relationships among Aβ, vascular risk (FCRP score), HDL cholesterol, and cortical thickness in elderly individuals with (PiB+) and without (PiB−) Aβ burden

Statistical cortical maps showing the association among Aβ, vascular risk (FCRP score), HDL cholesterol, and cortical thickness in PiB+, PiB−, and all older subjects. Cold colors (A–F) suggest that both increased vascular risk and increased Aβ burden are associated with thinner cortex. Warm colors (G–I) suggest that increased HDL cholesterol levels are associated with thicker cortex. Statistical surface maps were created using a vertex-wise statistical thresholds of p < 0.05. The analyses are corrected for age, cognitive status, and multiple comparisons. Aβ = β-amyloid; FCRP = Framingham Coronary Risk Profile; HDL = high-density lipoprotein; PiB = Pittsburgh compound B.

Figure 2. Independent effects of vascular risk (FCRP score) and HDL cholesterol on cortical thickness

(A) Statistical cortical maps showing the association between vascular risk (FCRP score) and cortical thickness while controlling for HDL cholesterol. (B) Statistical cortical maps showing the association between HDL cholesterol and cortical thickness while controlling for vascular risk. Cold colors suggest that increased vascular risk is associated with thinner cortex. Warm colors suggest that increased HDL cholesterol levels are associated with thicker cortex. Statistical surface maps were created using a vertex-wise statistical threshold of p < 0.05. Correction for multiple comparisons was done using Monte Carlo cluster-wise simulation repeated 1,000 times. FCRP = Framingham Coronary Risk Profile; HDL = high-density lipoprotein.