Perfusion Abnormalities In Mild Cognitive Impairment Measured By Arterial Spin Labeling MRI

Mild cognitive impairment (MCI) is regarded as a condition between normal aged people and dementia. Nearly 15-42% MCI patients convert to Alzheimer's Disease (AD) or other type of dementia every year. According to the different paradigms of cognitive impairments, MCI consists amnestic mild cognitive impairment (aMCI) and non-amnestic MCI (na-MCI). Besides, MCI can also be divided into mild cognitive impairment with single domain (MCI-SD) and mild cognitive impairmen with multiple domain (MCI-MD). aMCI is the most common type of MCI. Episodic memory loss is the predominant symptom in aMCI, while other cognitive domains remain relatively normal. Beginning with impaired memory, AD is featured by a progressive cognitive decreased, which would result in the loss of all intellectual functions inevitable, and even death. AD has become the leading role of causing dementia, with the rate of approximately 70%. As for the etiology of AD, which is rather complicated, and still unknown. The characteristic neuropathologic changes are described as accumulation of ?-amyloid plaques, neurofibrillary tangles, synaptic dysfunction and neuronal apoptosis. A series of risk factors, such as age, genetic factors, obesity, alcohol intake, cigarette smoking, diabetes, hypercholesterolemia and oxidative stress have played important roles in the pathogenesis of AD. To date, there is non effective cure for AD, while to prevent the decline of cognitive function as well as physical function, early diagnosis and medical treatment at the early stage of AD even MCI may let the patients back to normal congnitive function. Recent research has demonstrated the abnormalities of brain circulation of AD, either during task-induced neural activity at rest, are more commonly associated with Alzheimer's disease than was previously thought. Cerebral perfusion mainly been imaged by positron emission tomography (PET), single-photon emission computed tomography (SPECT), perfusion weighted MRI (PWI). PWI can be divided into two categories:(1) dynamic susceptibility contrast (DSC) that requires exogenous contrast tracers, and (2) arterial spin labeling, which does note requires exogenous contrast tracers. ASL uses inflowing water molecules in blood as an endogenous contrast agent. ASL does not involve radioactive media and thus provides a less invasive alternative to enable repeated applications with relative lower cost. Researches using ASL methods obtained the results in good agreement when compared to PET and SPECT researches. Above all, ASL MRI is a new emerging prospective field for providing research in neurodegenerate disease. Early outcomes of ASL MRI studies are general hypoperfusion pattern of the clinical AD, while only little research point to MCI, sometimes with small sample size and incomplete neuropsychological tests. Perfusion abnormalities in mild cognitive impairment measured by arterial spin labeling MRI need more research to provided idea and evidence of pathogenesis of MCI and AD.Objective:To investigate the perfusion abnormalities in mild cognitive impairment measured patients by arterial spin labeling MRI and to explore the relationship between cerebral perfusion characteristics and neuropsychological tests. Methods:We recruited 83 aMCI patients and 130 well matched healthy controls with age, gender and education. Full-scale neuropsychological tests were used to evaluate the cognitive function in these subjects including the cognitive domain of episodic memory, visuospatial function, information processing speed, and executive function. All participants underwent high-resolution T1-weighted anatomical images scan and ASL images scan. The T1-weighted anatomical and ASL images were preprocessed using the MATLAB programs. Then compared the relative cerebral blood flow(rCBF) using REST program. Set up the region of interests(ROI) manually for the following investigate of relationship between rCBF and congnitive function. Results:(1). aMCI patients exhibit significant lower neuropsychological tests scores compared to HC (P<0.001), including episodic memory, visuospatial function, information processing speed, and executive function. (2). The rCBF in left medial frontal gyrus, anterior cingulate, left middle occipital gyrus, left cuneus, left lingual gyrus, left calcarine is relativly higher in MCI(P<0.05). Hypoperfusion field were not found in the research. (3). The rCBF data of ROI introduced above were extracted, then the association between neuropsychological performance and rCBF (both single neuropsychological test score and cognitive domain Z score) were investigate. The altered rCBF in frontal lobule observed significant negative correlation to Clock Drawing Test (P=0.047, r=-0.22), Digital Symbol Substitution Test (P=0.030, r=-0.240) and Verbal Fluency Test (P=0.030, r=-0.240), while the change of rCBF in occipital lobule exhibit significant positive correlation to CDT(Plingual=0.046, ningual=0.221) and VFT(Ptingual=0.012, rlingual=0.275;Pcalcarine=0.035, rcalcarine=0.234). After separated the neuropsychological tests into 4 cognitive domains and transformed the raw scores into 4 composite Z scores, there were no significant correlation between Z score and rCBF of ROI. Conclusion:The research obtained the different perfusion paradigms between MCI and HC by ASL MRI. Compared to HC, MCI patients showed hyperperfusion in frontal lobe and occipital lobe. Altered rCBF in left medial frontal gyrus and anterior cingulate were associated with visuospatial function, information processing speed, and executive function, while left occipital lobules's rCBF were correlated to visuospatial function and executive function. aMCI patients showed higher CBF in occipital lobule to persuade the better visuospatial function and executive function, which maybe a term of compensatory mechanism of impaired neurons' function. The higher CBF in frontal lobule without better cognitive function suggests that frontal lobule take part in the compensation process at the beginning of the MCI continuum but eventually breaks down as symptoms increase in severity.