Introduction

Patients with asymptomatic carotid artery stenosis (CAS) reported cognitive impairments in general [1]. Recently, the CAS patients with reduced intrinsic (resting) functional connectivity (FC) were reported with declined cognitive performances [2]. However, recently we found that aberrant DMN connectivity indeed associated with stenosis severity, but not consonant with patients’ neuropsychological tests [3]. To explain the mismatch, we further probed the amplitude of low-frequency fluctuations (ALFF) across different CAS groups of unilateral & bilateral stenosis, and disclosed its relation with neuropsychological tests in this study.

Methods

We divided 60 patients into three different CAS types: unilateral stenosis (51-99%, n=18), unilateral occlusion (100%, n=28), and bilateral stenosis (n=14). Twenty-six normal controls were recruited for comparison. Resting-fMRI data were acquired at a 3T Trio scanner using EPI sequence for 5 minutes: TR/TE/FA=2000 ms/30 ms/90°, 33 slices with thickness of 3.4 mm (gap=1 mm), matrix: 64×64, and FOV=240×240 mm2. The patient data with unilateral stenosis in the left side were flipped inter-hemispherically to unify the affected side (right side). After the standard preprocessing steps (motion correction, denoise, normalization and smoothing), voxel-wise ALFF map (frequency range=0.01-0.08 Hz) was calculated using AFNI for each subject.The neuropsychological tests included: (1) Raven's Standard Progressive Matrices (SPM); (2) the Chinese Graded Word Reading Test (CGWRT); (3) the California Verbal Learning Test-II (CVLT-II) and the Brief Visual Memory Test-Revised (BVMT-R); (4) the Purdue Pegboard Test (PPT); (5) the Benton 3-Dimensional Construction Praxis Test (B3D); and (6) the Category Fluency Test (CFT) and Design Fluency Test (DFS). One-way ANOVA and associated post hoc tests were applied to the three patient groups for hypothesis testing.

Results

Figure 1a shows the significantly lower ALFF values in the stenosisgroup than those in the bilateral group. Compared to the control group, all patient groups showedsignificant differences in ALFF maps. The occlusion and bilateral groups showed stronger ALFF than control group (Fig.1c and 1d), whereas the stenosis group had lower ALFF than the control group (Fig.1b). Regarding tothe neuropsychological tests, the stenosis group had better performances than the occlusion group in only two sub-items (MoCA Fluency and Switch Accuracy) . Four sub-items (MMSE, MoCA, Purdue and Switch Accuracy) displayed significant differences between occlusion and healthy control groups. Moreover, significant differences in most of neuropsychological tests were found between the bilateral and the control groups (Table1).

Discussion and Conclusions

Aberrant ALFFs across different types of asymptomatic CAS was demonstrated for the first time. Interestingly, ALFF showed the most prominent changes between the stenosis and bilateral groups; however, only one of the neuropsychological tests showed significant difference on the same between-group comparison. Although the ALFF of CAS patients differed from that ofthe control group, most of significant differences of the neuropsychological tests were found between the bilateral and the control group. In other words, the between-group disparity of ALFF and neuropsychological tests did not consistently match.In conclusion, both ALFF and functional connectivity might not provide sufficient information to explain the cognitive impairments in CAS patients.

Acknowledgements

We thank the Magnetic Resonance Imaging Center of Linkou Chang Gung Memorial Hospital for their kind support in imaging arrangement. FundingThis study was carried out under the grants from the Ministry of Science and Technology, Taiwan (Grants MOST 107-2314-B-182A-053 -).