遗忘型轻度认知障碍基底前脑胆碱能通路弥散张量成像研究
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摘要
目的:利用弥散张量成像(diffusion tensor imaging,DTI)和基于骨架的空间统计方法(Tract-basedspatialstatistics,TBSS)等相关技术探究遗忘型轻度认知障碍者所存在的白质微结构改变,并探索硫胺素代谢对基底前脑胆碱能通路白质微结构的影响。方法:经筛查并临床诊断的32例遗忘型轻度认知障碍者及49例认知正常者进入本研究,进行TBSS和感兴趣区的弥散成像参数分析。其中22例遗忘型轻度认知障碍和19例认知正常者接受血硫胺素代谢产物定量检测,按照二磷酸硫胺素水平高低和三分位法将受试者分为3组进行单因素分析,探究硫胺素代谢产物水平对基底前脑胆碱能通路白质微结构的影响。结果:TBSS和感兴趣区分析并未发现遗忘型轻度认知障碍与认知正常对照者的各向异性分数、平均弥散度存在显著差异。而不同二磷酸硫胺素水平组在扣带束的各向异性分数、平均弥散度均值存在显著差异。结论:硫胺素代谢障碍或可解释扣带束白质微结构改变,支持其在阿尔茨海默病早期或对基底前脑胆碱能系统产生致病作用。
Objectives To investigate the microstructural alteration in white matter of cholinergic pathway of basal forebrainand its potential mechanisms in amnestic mild cognitive impairment(a MCI)patients as compared to cognitively normal subjects through diffusion tensor imaging(DTI) and tract-based spatial statistics(TBSS) analysis. Methods 32 a MCI patients and 49 cognitively normal subjects were recruited according to the inclusion and exclusion criteria in this study. TBSS and TBSS-based region of interest(ROI) analysis were performed. Among them, 22 aMCI patients and 19 cognitively normal subjects voluntarily accepted quantification test of blood thiamine metabolites. According to the levels of thiamine diphosphate, subjects were divided into three subgroups using three quantile method to conduct a univariate analysis. Results Both TBSS and ROI analysis showed no significant microstructural alteration between aM CIand normal subjects. The values of mean fractional anisotropy(FA) and mean diffusivity(MD) in cingulum were significant different among groups based on thiamine diphosphate levels. Conclusions The disturbance of thiamine metabolism may account for white matter microstructural alteration in cingulum, supporting its role in the pathogenesis ofbasal forebrain cholinergic system in early Alzheimer disease.
Objectives To investigate the microstructural alteration in white matter of cholinergic pathway of basal forebrainand its potential mechanisms in amnestic mild cognitive impairment(a MCI)patients as compared to cognitively normal subjects through diffusion tensor imaging(DTI) and tract-based spatial statistics(TBSS) analysis. Methods 32 a MCI patients and 49 cognitively normal subjects were recruited according to the inclusion and exclusion criteria in this study. TBSS and TBSS-based region of interest(ROI) analysis were performed. Among them, 22 aMCI patients and 19 cognitively normal subjects voluntarily accepted quantification test of blood thiamine metabolites. According to the levels of thiamine diphosphate, subjects were divided into three subgroups using three quantile method to conduct a univariate analysis. Results Both TBSS and ROI analysis showed no significant microstructural alteration between aM CIand normal subjects. The values of mean fractional anisotropy(FA) and mean diffusivity(MD) in cingulum were significant different among groups based on thiamine diphosphate levels. Conclusions The disturbance of thiamine metabolism may account for white matter microstructural alteration in cingulum, supporting its role in the pathogenesis ofbasal forebrain cholinergic system in early Alzheimer disease.
引文
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[3]Petersen R C,Roberts R O,Knopman D S,et al.Prevalence of mild cognitive impairment is higher in men The Mayo Clinic Study of Aging[J].Neurology,2010,75(10):889.
[4]Larrieu S,Letenneur L,Orgogozo J M,et al.Incidence and outcome of mild cognitive impairment in a population-based prospective cohort[J].Neurology,2002,59(10):1594-9.
[5]Petersen RC,Thomas RG,Grundman M,et al.Donepezil and vitamin E in the treatment of mild cognitive impairment.N Engl J Med.2005;352:2379-2388.
[6]Petersen R C,Parisi J E,Dickson D W,et al.Neuropathologic features of amnestic mild cognitive impairment.[J].Archives of Neurology,2006,63(5):665.
[7]Ferman T J,Smith G E,Kantarci K,et al.Nonamnestic mild cognitive impairment progresses to dementia with Lewy bodies[J].Neurology,2013,81(23):2032-2038.
[8]Molano J,Boeve B,Ferman T,et al.Mild cognitive impairment associated with limbic and neocortical Lewy body disease:a clinicopathological study[J].Brain AJournal of Neurology,2010,133(2):540-56.
[9]Nir T M,Jahanshad N,Villalonreina J E,et al.Effectiveness of regional DTI measures in distinguishing Alzheimer’sdisease,MCI,and normal aging[J].Neuroimage Clinical,2013,3:180.
[10]费国强.阿尔茨海默病患者全血硫胺素及其磷酸酯衍生物含量测定与苯磷硫胺干预的研究[D].复旦大学,2009.
[11]Caso F,Agosta F,Filippi M.Insights into White Matter Damage in Alzheimer’s Disease:From Postmortem to in vivo Diffusion Tensor MRI Studies[J].Neuro-degenerative diseases,2015,16.
[12]Brun A,Englund E.A white matter disorder in dementia of the Alzheimer type:a pathoanatomical study[J].Annals of Neurology,1986,19(3):253.
[13]Sm D L M.Quantitation of cerebral atrophy in preclinical and end-stage Alzheimer’s disease[J].Annals of Neurology,1989,25(5):450-9.
[14]Ballinger E C,Ananth M,Talmage D A,et al.Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline[J].Neuron,2016,91(6):1199.
[15]Whitehouse P J,Price D L,Struble R G,et al.Alzheimer’s disease and senile dementia:loss of neurons in the basal forebrain[J].Science,1982,215(4537):1237.
[16]Coyle J T,Price D L,Delong M R.Alzheimer’s Disease:A Disorder of Cortical Cholinergic Innervation[J].Science,1983,219(4589):1184.
[17]Geula C,Nagykery N,Nicholas A,et al.Early Cholinergic Neuronal and Axonal Pathology in Aging and Alzheimer’s Disease[J].Journal of Neuropathology&Experimental Neurology,2008,67(4):309.
[18]Mesulam M,Shaw P,Mash D,et al.Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-ADcontinuum.[J].Annals of Neurology,2004,55(6):815.
[19]Gilmor M L,Erickson J D,Varoqui H,et al.Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer’s disease.[J].Journal of Comparative Neurology,2015,411(4):693-704.
[20]桑绍明,万文斌,王子高,等.基于阿尔茨海默病病理生理特征之间关系再认识的新假说及其应用[C]//长三角地区神经科学论坛2016暨第八次会员代表大会摘要集.2016.
[21]喻秋剑,王昌鹏,钟春玖.膜衰老及其诱发的脑能量代谢异常是阿尔茨海默病发病机制的源头[J].中国医学前沿杂志:电子版,2016,8(11):4-6.
[22]Beaulieu C.What makes diffusion anisotropic in the nervous system?[M]//Jones DK.Diffusion MRI:theory,methods and applications.New York,NY:Oxford University Press;2011:p.92-109.