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Research Paper|Volume 12, Issue 14|pp 15058—15076

Cortical atrophy mediates the accumulating effects of vascular risk factors on cognitive decline in the Alzheimer’s disease spectrum

Qing Wang1, Cancan He1, Yao Zhu1, Qianqian Zhang1, Zhijun Zhang1,2, Chunming Xie1,2
  • 1Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China
  • 2Neuropsychiatric Institute, Affiliated Southeast University, Nanjing 210009, Jiangsu, China
* The data used in this article were obtained from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu/). As such, investigators within the ADNI contributed to the design and implementation of the ADNI and/or provided data but did not participate in the analysis or writing of this report. The following listing provides the ADNI investigators: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf
Received: January 13, 2020Accepted: June 13, 2020Published: July 29, 2020
https://doi.org/10.18632/aging.103573

Copyright: © 2020 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

There are increasing concerns regarding the association of vascular risk factors (VRFs) and cognitive decline in the Alzheimer's disease (AD) spectrum. Currently, we investigated whether the accumulating effects of VRFs influenced gray matter volumes and subsequently led to cognitive decline in the AD spectrum. Mediation analysis was used to explore the association among VRFs, cortical atrophy, and cognition in the AD spectrum. 123 AD spectrum were recruited and VRF scores were constructed. Multivariate linear regression analysis revealed that higher VRF scores were correlated with lower Mini-Mental State Examination scores and higher Alzheimer's Disease Assessment Scale-Cognitive Subscale scores, indicating higher VRF scores lead to severer cognitive decline in the AD spectrum. In addition, subjects with higher VRF scores suffered severe cortical atrophy, especially in medial prefrontal cortex and medial temporal lobe. More importantly, common circuits of VRFs- and cognitive decline associated with gray matter atrophy were identified. Further, using mediation analysis, we demonstrated that cortical atrophy regions significantly mediated the relationship between VRF scores and cognitive decline in the AD spectrum. These findings highlight the importance of accumulating risk in the vascular contribution to AD spectrum, and targeting VRFs may provide new strategies for the therapeutic and prevention of AD.