The Cerebrovascular Reactivity-Adjusted Spontaneous Brain Activity Abnormalities in White Matter Hyperintensities Related Cognitive Impairment: A Resting-State Functional MRI Study

Article type: Research Article

Authors: Ni, Ling^{a; b; 1} | Sun, Wenshan^{a; 1} | Yang, Dan^c | Huang, Lili^c | Shao, Pengfei^c | Wang, Chong^{c; *} | Xu, Yun^{a; c; *}

Affiliations: [a] Department of Neurology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China | [b] Department of Radiology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China | [c] Department of Neurology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China

Correspondence: [*] Correspondence to: Chong Wang and Yun Xu, Department of Neurology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. E-mails: xuyun20042001@aliyun.com (Xu) and wangchong0424@163.com (Wang).

Note: [1] These authors contributed equally to this work.

Abstract: Background:The BOLD signal is regulated by neuronal activity and vascular physiology. The evolution pattern of brain activities after modulating the vascular factors in white matter hyperintensities (WMHs) related cognitive impairment (CI) was unknown. Objective:To explore the “pure” low-frequency fluctuation (ALFF) alterations after adjusting the cerebrovascular reactivity (CVR) factor. Methods:In this study, 111 WMHs subjects including 55 with CI (WMH-CI) and 56 without CI (WMH-no-CI), and 72 normal controls (NCs) underwent resting-state fMRI. The CVR and ALFF maps were derived using BOLD data. A voxel-wise Pearson analysis was performed to detect the relationship between CVR and ALFF maps. The ANCOVA analysis with and without CVR as a covariate was conducted to explore the effect of CVR on ALFF analysis. Correlation between the ALFF alterations and cognitive performance was conducted in WMH-CI subjects. The receiver operating characteristic curve was constructed to assess the diagnostic performance of ALFF indexes to determine the occurrence of CI. Results:There was a significant widespread correlation between the CVR and ALFF maps. The ALFF alterations between the WMH groups and NC group with CVR as covariate were more than those without CVR as covariate. WMH-CI subjects showed further ALFF alterations when compared with WMH-no-CI subjects. The abnormal ALFF values were significantly associated with poor performance. The combination of inferior frontal gyrus and middle frontal gyrus to PCC provided an incremental contribution to the occurrence of CI. Conclusion:More areas with abnormal ALFF values which were specific to the WMHs related cognitive dysfunction were detected when considering the impact of CVR.

Keywords: Amplitude of low-frequency fluctuation, cerebrovascular reactivity, cognitive impairment, white matter hyperintensities

DOI: 10.3233/JAD-215216

Journal: Journal of Alzheimer's Disease, vol. 86, no. 2, pp. 691-701, 2022