A Preliminary Study Of Vascular Cognitive Impairment In Adult Patients With Moyamoya Disease

Adult patients with moyamoya disease (MMD) are commonly diagnosed with vascular cognitive impairment (VCI), the basic pathophysiological underlying nature of which is different from that of Alzheimer’s disease and mild cognitive impairment, indicating the cognitive domain of executive function/attention rather than memory to be primarily impaired. However, there is a lack of studies focusing on the reliability and validity of neuropsychological tests for VCI assessment. Most techniques adopted to detect VCI are structure-related and are not sensitive to subtle functional change following the impairment of neurocognition, thus fail to tell the correlation between the impairment of executive function/attention and hypoperfusion in the frontal gyrus, not to mention the early diagnosis of VCI or the evaluation of surgical treatment effectiveness. Therefore, new techniques are needed to effectively detect VCI, to provide insight into the intrinsic functional architecture, thus involving in the early diagnosis and treatment of VCI in adult MMD. In addition, surgical treatment has been proved efficacious in improving cerebral perfusion and decreasing neovessel formation, whereas its early cognitive outcome is not clear.The present study adopted the neuropsychological tests, functional MRI (fMRI), perfusion and structural imaging to investigate the VCI in adult patients with MMD. In Part I, a battery of neuropsychological tests was developed for VCI by comparing the reliability and validity of various tests designed for the same cognitive domain. In Part II, we achieved technological innovation by analyzing the correlation between the neuropsychological assessment and resting-state blood oxygen level-dependent (BOLD) fMRI. In Part III, we investigated the postoperative improvement of cognition by combining the neuropsychological tests with resting-state BOLD fMRI, perfusion and structural imaging and proved its feasibility.Part I:Development of a battery of neuropsychological tests for VCIThe term VCI is used to identify patients with ischemic cerebrovascular diseases (ICVD) who develop cognitive impairment thereafter, including MMD. A battery of standardized neuropsychological tests was administered in a cohort of consecutive patients with cerebral ischemia. According to the screening results, patients were divided into 3 subgroups of vascular dementia (VaD), vascular mild cognitive impariment (VaMCI) and non-VCI. Fifty-six patients and 48 healthy subjects (normal control group) were recruited. In the case group,58.9% of patients were with VCI, including 19.6% of VaD and 39.3% of VaMCI, the rate of VaD/VaMCI was 1/2. All patients in the VaMCI subgroup presented with deficit of at least 1 certain executive function/attention index and all VaMCI cases presented with comprehensive cognitive impairment. There was no significant difference among the 3 subgroups of the type of ischemia (x 2= 1.111, P= 0.574). In the case group,56.7% of patients with stroke suffered from VCI and the rate of VaMCI/VCI was 58.8%; and 61.5% of patients with transient ischemic attack (TLA) suffered from VCI and the rate of VaMCI/VCI was 75.0%.In this section, a battery of neuropsychological tests was developed for VCI by assessing cognitive impairment in patients with ICVD. We also found that patients with TIA were less impaired than those with stroke, implying that early treatment may improve patients’cognition.Part Ⅱ: Localization of cortical function in adult MMD patients with VCIA battery of neuropsychological tests and resting-state BOLD fMRI were administered to participants.47.8% of the 23 adult patients were with VCI (VCI subgroup) and 52.2% were not (NonVCI subgroup). Results indicate that the most significant differences in the amplitude of low-frequency fluctuations (ALFF) were observed in such regions as the prefrontal gyrus (PFG), anterior cingulate cortex (ACC) and the right supplemental motor area (SMA). Then we found that the right middle frontal gyrus (MFG), the right SMA, bilateral ACC and the orbitofrontal gyrus (OFG) showed the most significant correlation with MMSE scores. Furthermore, positive correlation with MMSE scores was found in bilateral IPL, SPL and left CN, while negative correlation was found in bilateral precuneus (PCu).In this section, the resting-state BOLD fMRI was proved sensitive for early detection of cognitive impairment in patients with MMD. What’s more, we provide the functional brain map which was related to anatomical structures of adult MMD and its correlation with VCI, thus providing not only insights into biological mechanisms of this disease, but also the possibility to detect further improvement of VCI after treatment.Part III:Therapeutic effect assessment of surgical revascularization for VCI in adult patients with MMDBoth neuropsychological tests and resting-state BOLD fMRI were proved sensitive for early detection of cognitive impairment in adult patients with MMD. We recruit 44 adult MMD patients, including 34 receiving surgical revascularization and 10 receiving conservative treatment, as well as 10 healthy subjects. Cognitive assessment was performed before the operation and during the early follow-up. Significant differences among the 3 groups were observed in the improvement of MES and MES-EX during early follow-up, and the surgery group improved the most. Also, significant differences among the VaD, VaMCI and NonVCI subgroups were observed in the surgery group, with the VaD subgroup improving the most. Patients with perioperative complications suffered from less improvement of MMSE and MES scores, whereas there was no significant difference among the 3 subgroups during early follow-up. For the evaluation of postoperative collateral grading on external carotid angiography,67.6% of the surgery group scored grade A, indicating that more than 2/3 of the MCA territory was perfused, while 23.5% scored grade B, indicating between 1/3 and 2/3 was perfused, and the rest 8.9% scored grade C, indicating less than 1/3 was perfused. There was significant correlation between the increase of postoperative MES score and the improvement of perfusion in the surgical hemisphere.In this section, the assessment instruments we combined were proved feasible. Also, the postoperative improvement of cognition was briefly analyzed, indicating the consistency of improvement of perfusion and cognition.The novelty of this study1. For the first time, a systematic battery of neuropsychological tests was developed for VCI, which was then used to investigate the impairment of cognitive domains in TIA.2. For the first time, we provide the functional brain map which was related to anatomical structures of adult MMD with VCI.3. For the first time, we reported the functional connectivity and resting-state networks in adult patients with MMD and their correlation with VCI.4. For the first time, we evaluated the postoperative improvement of cognition in adult patients with MMD by the use of neuropsychological tests, resting-state BOLD fMRI, perfusion and structural imaging.