| 其他摘要 | In the past ten years, a major transition of the research interests in cognitive impairment field has taken place, from the investigation of the pathological and biochemical mechanisms to the detection and prevention of the mild cognitive impairment (MCI), the preclinical stages of dementia. The development of elderly cognitive impairment could be a long process, probably beginning years before the clinical symptoms. Most investigators believe that if we wait for functional impairment, and perhaps even mild cognitive symptoms, to emerge, it may be too late to treat the underlying disease process. Ideally, if we could detect and prevent or postpone the disease process by intervening early, we could largely improve the life quality of the patients and reduce the expenses for both government and family per se. Exploring the sensitive makers for MCI detection from multi-dimensional and levels has become the hot issues in worldwide. There are four dimensions to detect MCI and early dementia: clinical scales, neuropsychological tests, neuroimaging, and biomarkers. As such, certain markers may be differentially sensitive and informative at different stages in the underlying progression of the diseases. No single measures will be uniformly predictive throughout the entire disease process. The present research based on the National Key Technology R&D Program of China directed by both Shanghai Mental Health Center and our lab: Mental health evaluation, warning system and intervention project on Chinese older adults. This project is a population-based study, including neuropsychological tests, clinical diagnosis, serial blood, urine samples and when applicable, neuroimaging examinations. This large database provides us the possibilities to investigate the different markers for Chinese MCI detection. In present study, we investigate the accuracy of biomarker (endogenous formaldehyde), brief neuropsychological test (Beijing version of Montreal cognitive assessment), and neuroimaging (delayed-match-to sample task, DMST) to screen the MCI in Chinese older adults. Our hypothesis is, if we use the convenient biomarkers from peripheral nervous system to do the initial screen, and use the neuropsychological test to do the individual screening for the potential subjects who was detected by the initial screening, and finally we use neuroimaging examination to diagnose every single patient. From these processes, the accuracy of the detection will be much more improved and more efficient. In studyⅠ, we analyzed formaldehyde level by high-performance liquid chromatography to investigate the correlation of endogenous formaldehyde in urine of older adults and their cognitive ability. The results showed the endogenous formaldehyde was negatively correlated with general cognitive ability, and this correlation was moderated by individual’s educational level. Because of the instability of human’s endogenous formaldehyde, this biomarker from peripheral nervous system was not suitable for using in the diagnosis of MCI at this point of time. In study Ⅱ, we examined the sensitivity and specificity of MoCA-BJ screening for MCI in a community-based population residing in both urban and rural areas of Beijing. Moreover, detailed analyses including item analysis, examination of the optimal cut-off scores, area analysis, and the comparison with the MMSE were performed. The MoCA-BJ, in general, is a relatively mediocre screening tool for detecting MCI and could be recommended to clinicians for reference. Specific items of MoCA-BJ limited by culture and education should be modified in the future to achieve more ideal detection performance of MCI. In study Ⅲ, we used functional MRI (fMRI) to examine the brain activations and brain functional connectivity in specific regions while the subjects are performing the DMST which included both explicit and implicit memory, and further to find out how the mild cognitive impairment affected in these activations and connectivity. The results showed the MCI group demonstrated impaired explicit memory, but relatively intact implicit memory (distractor repetition). Using the most impaired activation changes in caudate and left inferior frontal gyrus as the central nervous markers, the sensitivity and specificity for MCI detection can reach to 90% and 70%, respectively. In current studies, due to the instability of endogenous formaldehyde as the biomarker from peripheral nervous system, and the MoCA-BJ in which some items still need further modification, we didn’t find much better indexes for MCI screening accuracy when combined the three markers. In future research, we can investigate some other biomarkers with more stable and sensitive characteristics, combined with modified MoCA-BJ and suitable fMRI tasks. In this way, we could expect much more improvement in the accuracy of Chinese elderly MCI screening. |
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