The Effect Of ApoE Gene And Altered Brain Structures On The Cognitive Disfuntion Of CNS Demyelinating Diseases

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are the relatively common demyelinating diseases of the central nervous system (CNS). Limb weakness, sensory and visual abnormalities are the common clinical symptoms as well as cognitive dysfunctions. Nearly half of them presented with cognitive dysfunctions and they were multi-factors involved. Among them, apolipoprotein E (ApoE) s4 allele may play a role in the pathogenesis of cognitive impairment in MS, and there exists controversy whether the cerebral gray matter (GM) or white matter (WM) lesions are responsible for the cognitive dysfunctions. To further explore the mechanism about the cognitive impairments, we utilized genetic detection and multi-model MRI advanced techniques, which will be helpful to take targeted interventions for the cognitive impairments.Content Study 1:Cognitions were assessed in MS patients, ApoE alleles were identified and diffusion tensor imaging combining with voxel-based morphology were performed to study whether the ApoE e4 allele affected their cognitions and cerebral structures, and whether there existed differences in cerebral structures of MS patients with different cognitive levels. Study 2:To analyze the characteristics of cognitive functions and brain structural substrates of cognitive dysfunctions in NMO patients.Results Study 1:① Compared with healthy controls (HCs), MS patents displayed impaired cognitions on information processing speed and working memory. Years of education, EDSS, HAMA and HAMD scores correlated with multiple cognitive domains, age correlates with verbal fluency, disease duration correlates with learning and memory. Extensive micro-structural abnormalities were detected in the WM of patients with MS, and decreased GM densities were also found in right insula, inferior frontal gyrus, middle frontal gyrus and left cingulate gyrus. ② Fourteen MS patients were classified as CI (35.9%), and the rest were CP. CI patients had lower education level and the EDSS, HAMA and HAMD scores were higher than CP patients. Patients with CI performed worse on verbal fluency, information processing speed, visual memory and executive functions compared with CP patients. EDSS score was the risk factor of cognitive impairment for MS patients. Compared to CP patients, widespread impairments of WM integrity were found and several brain areas showed density reduced in bilateral caudate, left insula and right temporal lobe in CI patients. ③ The numbers of patients with MS in ApoE ε4+ group and ε4-group were 10 (25.64%) and 29, respectively. Language and visual memory, information processing speed and working memory of ε4+ group were worse compared with those of ε4- group, but no significant differences in diffusion metrics and GM density were detected between the two groups.Study 2: ① Information processing speed and working memory in NMO patients decreased significantly compared with HCs. All cognitive scores correlated with the years of education. Disease duration negatively correlated with episodic memory and executive function negatively correlated with HAMD scores. ② Patients with NMO showed widespread damages in many white matter tracts, while there were no significant differences in GM density between the NMO patients and HCs.Conclusion ① There exist changes of cognitive function both in MS and NMO patients. The impairment of WM integrity and the changes of GM density are thought to attribute to the cognitive impairments in MS patients, while only WM integrity damage maybe involved in the cognitive changes in NMO patients for them no changes of GM density were found. ② The white matter and grey matter changes were similar whether the ApoE ε4 positive or not, while the cognition function of MS patient was worse if the ApoE ε4 was positive. So, ApoE ε4 allele plays a role in the formation of cognitive impairments in MS patients.