嗅觉功能磁共振成像诊断MCI及早期AD的应用研究

发布时间：2018-04-23 19:58

本文选题：轻度认知障碍 + 阿尔兹海默病　；参考：《天津医科大学》2017年硕士论文

【摘要】：目的:愉快气味(pleasant odor,PO)与非愉快气味(unpleasant odor,UPO)刺激时嗅觉相关脑区的活化存在差异,目前尚无联合应用PO和UPO评估轻度认知障碍(mild cognitive impairment,MCI)和阿尔兹海默病(Alzheimer’s disease,AD)的研究。1应用优化嗅觉fMRI技术,分析PO和UPO在正常年轻人全脑和嗅觉相关感兴趣区(region of interest associated with olfactory,ROIawo)的激活差异;2比较正常老年组(normal control eldly person,NC)吸入PO和UPO后全脑和ROIawo的激活差异及与年轻组的异同,评估年龄因素对嗅觉中枢的影响,寻找反映NC嗅觉功能减退的fMRI指标;3比较NC、MCI和AD患者吸入两种气味后全脑和ROIawo激活差异,探索其与临床嗅觉功能评价及嗅觉行为学间的关系,评价联合应用PO和UPO嗅觉fMRI诊断MCI和AD的价值,寻找早期诊断AD的生物学指标。对象与方法:嗅觉正常年轻人(20例,男10例,女10例)和NC(25例,男11例,女14例)。采用Siemens Trio a Tim 3.0T磁共振扫描仪,通过嗅觉刺激器,采用事件相关设计方式呈现嗅觉刺激。选取双侧初级嗅觉皮层(primary olfactory cortex,POC)、海马和眶额回为ROIawo,提取各ROIawo内的激活体素数。比较吸入PO和UPO时全脑激活情况及各ROIawo激活体素数的差异。比较NC与正常年轻人嗅觉fMRI结果的异同。MCI(26例,男9例,女17例)和AD患者(22例,男9例,女13例),以NC为对照组。三组均接受神经心理学量表、嗅觉主观测评、载脂蛋白E(APOE)ε4等位基因、尿AD相关性神经丝蛋白(AD7c-NTP)等检测。嗅觉fMRI检查步骤同上。比较吸入PO和UPO时三组全脑激活情况及各ROIawo激活体素数的差异;分析三组受试者神经心理学量表、嗅觉主观测评等检查结果与嗅觉fMRI结果的相关性;比较吸入两种气味时三组行为学数据的异同。结果:年轻组两种气味刺激时全脑激活的脑区基本相似,UPO较PO全脑激活范围更明显(P=0.01)。NC全脑激活方式与年轻组类似,其活化脑区的范围小于年轻组。年轻组ROIawo激活情况:于POC区(Z=-1.972,P=0.049)和额下回眶部(Z=-2.167,P=0.03),UPO与PO激活体素数存在差异,前者大于后者;于海马和余眶额回,两者无差异(P0.05)。NC组ROIawo激活情况:于额下回眶部(Z=-2.178,P=0.029),UPO与PO激活体素数存在差异,前者大于后者;于POC、海马和余眶额回,两者无差异(P0.05)。MCI和AD组ROIawo激活情况:于所有ROIawo,UPO与PO激活体素数均无差异(P0.05)。NC、MCI和AD组两种气味刺激时全脑激活范围均呈递减趋势。NC、MCI和AD组不同浓度(0.10%,0.33%,1.00%)POC激活:PO刺激时,NC随浓度升高,POC激活体素数先增后减,而MCI和AD组随浓度升高逐渐增多;UPO刺激时,NC随浓度升高POC激活体素数逐渐减少,MCI和AD组随浓度升高依次增多。控制年龄因素时,三组受试者吸入PO和UPO后,POC激活水平与MOCA评分呈正相关(r=0.277,r=0.342,P0.05),与嗅觉识别阈值评分呈负相关(r=-0.391,-0.371,P0.01);额下回眶部激活水平与MOCA评分呈正相关(r=0.227,P0.05;r=0.331,P0.05),与嗅觉识别阈值评分呈负相关(r=-0.412,r=-0.316,P0.05)。PO刺激时,三组受试者行为学变化形式无差异(χ2=5.681,P=0.058);UPO刺激时,三组受试者行为学变化形式存在差异(χ2=31.275,P=0.000)。两两比较发现:NC组与MCI组(χ2=7.209,P=0.027)、NC组与AD组(χ2=23.794,P=0.000)、MCI组与AD组(χ2=15.520,P=0.000)均存在差异。结论:无论年轻组还是NC,UPO较PO激活脑区的范围更大。NC活化的脑区范围减小,提示随着年龄增长嗅觉功能的减退。年轻组吸入两种气味时于POC区和额下回眶部激活体素数存在差异,而NC仅在额下回眶部存在差异,可能反映了嗅觉功能减退的自然进程。与NC组相比,MCI和AD组吸入两种气味时ROIawo激活体素数均无差异,推测与AD病理改变累及ROIawo相关。吸入PO和UPO时额下回眶部激活体素数的差异性可以成为区分NC和MCI的生物学指标。随气味浓度的增加,POC区的激活模式显示NC组产生了嗅觉适应;而MCI和AD组均未产生。吸入UPO时POC区的激活模式能够区分NC和MCI,可作为发现MCI的生物学指标。两种气味嗅觉fMRI结果与嗅觉主观评分、临床量表均有相关性,提示吸入PO和UPO的嗅觉f MRI均可评估嗅觉障碍以及与之相关的AD临床进程。吸入UPO后出现呼吸调整的行为学改变,能够反映与个体病情相关的嗅觉障碍的程度,为临床评测嗅觉功能诊断早期AD提供了新方向。综上所述,与单纯PO嗅觉fMRI比较,联合应用PO和UPO的嗅觉fMRI更有助于MCI和AD的评估。
[Abstract]:Objective: pleasant odor (PO) and non pleasant odors (unpleasant odor, UPO) stimulate the difference in the activation of the olfactory related brain regions. There is no joint application of PO and UPO to evaluate mild cognitive impairment (mild cognitive impairment, MCI) and Alzheimer's disease. Analysis of activation differences between PO and UPO in normal young people's whole brain and olfactory related region of interest (region of interest associated with olfactory, ROIawo). 2 compare the activation difference between the normal aged group (normal control eldly) and the activation difference between the whole brain and the younger group as well as the similarities and differences with the young group, and evaluate the shadow of the olfactory center by the age factors. To find the fMRI index reflecting the impairment of NC's olfactory function; 3 compare the difference in the activation of the whole brain and ROIawo after the inhalation of two odors in NC, MCI and AD patients, explore the relationship between the clinical olfactory function evaluation and the olfactory behavior, evaluate the value of the combined application of PO and UPO fMRI diagnosis MCI and AD, and find the biological indicators of the early diagnosis of AD. Objects and Methods: 20 cases of olfactory normal young people (20 cases, 10 men, 10 women) and NC (25 cases, 11 men, 14 cases). Using the Siemens Trio a Tim 3.0T magnetic resonance scanner, the olfactory stimulation was presented by the olfactory stimulator. The bilateral primary olfactory cortex (primary olfactory cortex, POC) was selected and the hippocampus and the orbital frontal gyrus were ROIawo. The number of activator primes within each ROIawo. Comparison of the whole brain activation and the difference in the prime number of ROIawo activator when inhaling PO and UPO. Compare the similarities and differences of.MCI (26 cases, 9 men, 17 women) and AD patients with NC and normal young people (22 cases, 9 men, 13 women), and NC as the pair. The three groups all accept the neuropsychological scale, the subjective evaluation of olfactory sense, The apolipoprotein E (APOE) 4 allele, the urine AD related neurofilament protein (AD7c-NTP) and other tests. The olfactory fMRI examination procedure was the same. The difference in the total brain activation and the number of ROIawo activator in the three groups was compared with the inhalation of PO and UPO, and the examination results of the three groups of subjects, the subjective evaluation of olfactory sense and the phase of the olfactory fMRI results were analyzed. The difference between the three groups of behavioral data was compared with the two kinds of scent inhalation. Results: the brain area activated by the whole brain was basically similar in the young group with two kinds of odor stimulation. UPO was more obvious than the PO whole brain activation range (P=0.01), the activation of the whole brain was similar to that of the young group. The activation of the brain area was less than that of the young group. The activation of ROIawo in the young group was in the POC region (Z= -1.972, P=0.049) and the orbital part of the lower frontal gyrus (Z=-2.167, P=0.03), the number of UPO and PO activator differences, the former is greater than the latter, and there is no difference (P0.05).NC group ROIawo activation in the hippocampus and the residual orbital frontal gyrus, in the lower frontal gyrus (Z=-2.178, P=0.029) in the lower frontal gyrus (Z=-2.178, P=0.029), the former is greater than the latter, hippocampus and residual orbital frontal gyrus, There is no difference (P0.05).MCI and AD group ROIawo activation: all ROIawo, UPO and PO activator primes are not different (P0.05).NC, MCI and AD group of two kinds of odor stimulation of the whole brain activation range is subtraction.NC, the concentration of different concentrations (0.10%, 0.33%, 1%) activation: when the stimulation, the concentration increases with the concentration, the activation body prime number first then decrease While the concentration of MCI and AD increased gradually with the increase of concentration, when the concentration of NC increased with the increase of UPO concentration, the number of POC activator decreased gradually, and the MCI and AD groups increased with the increase of concentration. The activation level of POC was positively correlated with MOCA score in the three groups of subjects when PO and UPO were inhaled (r= 0.277), and a negative phase with the olfactory recognition threshold score. (r=-0.391, -0.371, P0.01); the level of the orbital activation in the lower frontal gyrus was positively correlated with the MOCA score (r=0.227, P0.05; r=0.331, P0.05). There was a negative correlation between the threshold score of the olfactory recognition threshold (r=-0.412, r=-0.316, P0.05), and there was no difference in the form of behavioral changes in the three groups. There were differences (x 2=31.275, P=0.000). 22 the difference between group NC and MCI group (x 2=7.209, P=0.027), NC group and AD group (x 2=23.794, P=0.000), MCI group and AD group were different. The number of activating body primes in the POC area and the lower frontal gyrus was different in the young group when inhaling two kinds of odors, while the NC only in the orbital part of the lower frontal gyrus was different, which may reflect the natural process of the impairment of the olfactory function. Compared with the group NC, there was no difference in the number of ROIawo activator primes in the MCI and AD groups when they inhaled the two odors, presumably with the pathological changes of the AD. The difference in the number of activator primes in the orbital part of the frontal inferior frontal gyrus when inhaled PO and UPO could be a biological indicator to distinguish between NC and MCI. With the increase of the odor concentration, the activation mode of the POC region showed that the NC group produced the olfactory adaptation; both the MCI and AD groups did not produce. The activation mode of the POC zone in UPO was able to distinguish between NC and UPO when inhaling UPO. The two odors fMRI results were related to the subjective score of olfactory and the clinical scale, suggesting that the olfactory f MRI inhaled PO and UPO can evaluate the olfactory disorder and the associated AD clinical process. The behavioral changes of breathing adjustment after inhaling UPO can reflect the degree of olfactory disorder associated with the individual condition, It provides a new direction for the diagnosis of early AD in the diagnosis of olfactory function. To sum up, compared with the simple PO olfactory fMRI, the combination of PO and UPO's olfactory fMRI is more helpful to the assessment of MCI and AD.

【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R445.2;R749.16

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