| Objective:The current diagnosis criterion of vascular cognitive impairment (VCI) is based on the data of Alzheimer's disease, so it is difficult to detect and therapy VCI early. In this research, to investigate the characteristics of event-related potential (ERP) of visual-spatial working memory in patients with ischemic leukoencephalopathy, in order to explore new diagnostic methods to detect VCI early.Methods:According to the degree of ischemic white matter lesions on the conventional brain Magnetic Resonance Imaging (MRI), 24 patients with ischemic leukoencephalopathy (13/11 patients with mild/severe) and 12 healthy elders were recruited. All the participants performed a serial of neuropsychological scales(The Neuropsychiatric Inventory; Hamilton depression scale; Instrumental activity of daily living; Hachinski Inchemic Score; Montreal Cognitive Assessment (MoCA); Wechsler adult intelligence scale-Revised in China (WAIS-RC)-digit span, digit symbol, picture completion and block design; Trail making test A; Verbal fluency test). The ERP of visual-spatial working memory from the delayed matching-to-sample task was induced and diffusion tensor imaging was obtained.Results:1.General Cognition Assessment(1) Comparative to the Norm: On the total score of MoCA and the Trail making test A, normal cognition appears in the control group (26.00±1.94 and 61.70±18.29ms); Cognitive impairment appears in the mild group (23.31±3.68 and 89.00±52.46 ms) and severe group (21.27±4.41 and 117.82±57.92 ms). On the Verbal fluency test, normal cognition appears in the three groups (42.80±7.10, 37.23±6.46, 32.82±6.84).(2) Comparative to the control group: On the abstraction in MoCA, the score in the mild group(p<0.05)and severe group(p=0.52)was significantly lower than that in the control group, and there was no difference between the left two groups. On the inversed digit span in WAIS-RC, the score in the severe group was significantly lower than that in the mild group, and there was no difference between the left two groups. On the ordered digit span, digit symbol, picture completion and block design, higher the degree of ischemic white matter lesions was, poorer the performance was, but there were no differences among the three groups.2.The Analyses of Event-related PotentialThree waves were identified in delay phrase: N330, P420 and late negative component. On the two-ball-load, the N330 amplitude in the middle frontal, right frontal and occipital lobe was significantly smaller in the mild group (all, p<0.01) and in the severe group (all, p<0.05) than that in the normal control, and there was no difference between the two groups of patients. The N330 amplitude in the left frontal lobe, central region, left temporal lobe(the three parts, p<0.05)and parietal lobe(p<0.01)was significantly smaller in the mild group than that in the normal control, and there was no difference between the others. On the left targets of ERP, there were no differential markers between the patients with ischemic leukoencephalopathy and the control group.3.The Observation by Diffusion Tensor Imaging on the Patients with Ischemic LeukoencephalopathyOn the pars geniculate and posterior limb of the left internal capsule, the FA value was significantly smaller in the severe group than that in the mild group and control group, and there was no difference between the two others. On the left putamen and left pallidum, the ADC value was significantly smaller in the mild group and control group than that in the severe group. On the right putamen, the ADC value was significantly smaller in the control group than that in the severe group. On the right pallidum, the ADC value was significantly smaller in the mild group than that in the severe group. On the posterior limb of the left internal capsule, the ADC value was significantly smaller in the control group than that in the mild and severe group. In all above comparisons, there was no difference between the two others.4.The correlation analyses between the N330 amplitude and neuropsychological scalesAcross the 24 patients with ischemic leukoencephalopathy, in the middle frontal, right frontal and occipital lobe, the N330 amplitude was significantly correlated to the delay recall in MoCA. In the middle frontal, right frontal, occipital, parietal and right temporal lobe, the N330 amplitude was significantly correlated to the Trail making test A. In the middle frontal, right frontal, occipital, parietal, left and right temporal lobe, the N330 amplitude was significantly correlated to the digit symbol in WAIS-RC. In the occipital lobe, the N330 amplitude was significantly correlated to the ordered digit in WAIS-RC.5.The correlation and regression analyses between DTI data and neuropsychological scales(1) The FA value: only the posterior limb of the right internal capsule entered into the regression equation of the visual-spatial/execution, delay recall and total score in MoCA and the Trail making test A. Only the posterior limb of the right internal capsule was significantly correlated to attention in MoCA and picture completion in WAIS-RC. Only the left pallidum was significantly correlated to language in MoCA. Only the right thalamus entered into the regression equation of the inversed digit span in WAIS-RC. Only the pars geniculate of the right internal capsule was significantly correlated to digit symbol in WAIS-RC.(2) The ADC value: only the pars geniculate of the right internal capsule entered into the regression equation of the delay recall and total score in MoCA. Only the right putamen entered into the regression equation of the visual-spatial/execution in MoCA. Only the anterior limb of the left internal capsule entered into the regression equation of the abstraction in MoCA. Only the left thalamus entered into the regression equation of the orientation in MoCA. By turns, the pars geniculate of the right internal capsule and the right pallidum entered into the regression equation of the Trail making test A. By turns, the posterior limb of right internal capsule and the pars geniculate of the left internal capsule entered into the regression equation of the Verbal fluency test. Only the left pallidum entered into the regression equation of the inversed digit span in WAIS-RC. Only right anterior horn of lateral ventricle entered into the regression equation of the digit symbol in WAIS-RC. Only left putamen entered into the regression equation of the picture completion in WAIS-RC.6.The correlation and regression analyses between DTI data and the N330 amplitudeOnly the FA value of the posterior limb of the right internal capsule entered into the regression equation of the N330 amplitude in the right frontal lobe and was significantly correlated to the N330 amplitude in the middle frontal lobe. The FA value of the right putamen was significantly correlated to the N330 amplitude in five of eight brain regions (left frontal, central region, parietal, occipital, and right temporal lobe). The FA of the right globus pallidus and the left caudate nucleus and the ADC of the left posterior horn of lateral ventricle were significantly correlated to the N330 amplitude in the left temporal lobe. The FA of the right putamen and the left caudate nucleus were significantly correlated to the N330 amplitude in the right temporal lobe. Conclusions:1 . Patients with ischemic leukoencephalopathy: general cognitive impairment (Montreal Cognitive Assessment); visual spatial deficit (Trail making test A); Verbal fluency ability was reserved (Verbal fluency test). Comparative to the control group, patients with ischemic leukoencephalopathy: abstraction ability deficit (Montreal Cognitive Assessment: abstraction); deficit in visual-spatial working memory (the N330 amplitude in the middle frontal, right frontal and occipital lobe); working memory in the patients with severe ischemic leukoencephalopathy was lower than that in the patients with mild ischemic leukoencephalopathy (WAIS-RC- inversed digit span).2.Montreal Cognitive Assessment and Trail making test A were sensitive to the evaluation of the cognitive impairment for the patients with mild ischemic leukoencephalopathy.3.The N330 amplitude in delay phrase - ERP of visual-spatial working memory from the delayed matching-to-sample task was suitable to the cognitive evaluation for the patients with ischemic leukoencephalopathy.4.In the middle frontal, right frontal and occipital lobe, the significant decrease of N330 amplitude is the characteristic of ERP, which is based on the ischemic white matter lesions and become an electrophysiological indicator for the deficit in visual-spatial working memory in patients with ischemic leukoencephalopathy. The pathological mechanism of the characteristic of ERP was the ischemic lesions of projection fibers through the right internal capsule posterior limb.5.Diffusion tensor imaging can detect the potential changes which appear normal on the MRI, and reflect the damage in the fronto-subcortical circuits.6.Visual-spatial working memory is dependent on the integrity of dorsolatera prefrontal circuit.
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