本文選題：輕度認(rèn)知障礙 + 阿爾茲海默病��； 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:愉快氣味(pleasant odor,PO)與非愉快氣味(unpleasant odor,UPO)刺激時嗅覺相關(guān)腦區(qū)的活化存在差異,目前尚無聯(lián)合應(yīng)用PO和UPO評估輕度認(rèn)知障礙(mild cognitive impairment,MCI)和阿爾茲海默病(Alzheimer’s disease,AD)的研究。1應(yīng)用優(yōu)化嗅覺fMRI技術(shù),分析PO和UPO在正常年輕人全腦和嗅覺相關(guān)感興趣區(qū)(region of interest associated with olfactory,ROIawo)的激活差異;2比較正常老年組(normal control eldly person,NC)吸入PO和UPO后全腦和ROIawo的激活差異及與年輕組的異同,評估年齡因素對嗅覺中樞的影響,尋找反映NC嗅覺功能減退的fMRI指標(biāo);3比較NC、MCI和AD患者吸入兩種氣味后全腦和ROIawo激活差異,探索其與臨床嗅覺功能評價及嗅覺行為學(xué)間的關(guān)系,評價聯(lián)合應(yīng)用PO和UPO嗅覺fMRI診斷MCI和AD的價值,尋找早期診斷AD的生物學(xué)指標(biāo)。對象與方法:嗅覺正常年輕人(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磁共振掃描儀,通過嗅覺刺激器,采用事件相關(guān)設(shè)計方式呈現(xiàn)嗅覺刺激。選取雙側(cè)初級嗅覺皮層(primary olfactory cortex,POC)、海馬和眶額回為ROIawo,提取各ROIawo內(nèi)的激活體素數(shù)。比較吸入PO和UPO時全腦激活情況及各ROIawo激活體素數(shù)的差異。比較NC與正常年輕人嗅覺fMRI結(jié)果的異同。MCI(26例,男9例,女17例)和AD患者(22例,男9例,女13例),以NC為對照組。三組均接受神經(jīng)心理學(xué)量表、嗅覺主觀測評、載脂蛋白E(APOE)ε4等位基因、尿AD相關(guān)性神經(jīng)絲蛋白(AD7c-NTP)等檢測。嗅覺fMRI檢查步驟同上。比較吸入PO和UPO時三組全腦激活情況及各ROIawo激活體素數(shù)的差異;分析三組受試者神經(jīng)心理學(xué)量表、嗅覺主觀測評等檢查結(jié)果與嗅覺fMRI結(jié)果的相關(guān)性;比較吸入兩種氣味時三組行為學(xué)數(shù)據(jù)的異同。結(jié)果:年輕組兩種氣味刺激時全腦激活的腦區(qū)基本相似,UPO較PO全腦激活范圍更明顯(P=0.01)。NC全腦激活方式與年輕組類似,其活化腦區(qū)的范圍小于年輕組。年輕組ROIawo激活情況:于POC區(qū)(Z=-1.972,P=0.049)和額下回眶部(Z=-2.167,P=0.03),UPO與PO激活體素數(shù)存在差異,前者大于后者;于海馬和余眶額回,兩者無差異(P0.05)。NC組ROIawo激活情況:于額下回眶部(Z=-2.178,P=0.029),UPO與PO激活體素數(shù)存在差異,前者大于后者;于POC、海馬和余眶額回,兩者無差異(P0.05)。MCI和AD組ROIawo激活情況:于所有ROIawo,UPO與PO激活體素數(shù)均無差異(P0.05)。NC、MCI和AD組兩種氣味刺激時全腦激活范圍均呈遞減趨勢。NC、MCI和AD組不同濃度(0.10%,0.33%,1.00%)POC激活:PO刺激時,NC隨濃度升高,POC激活體素數(shù)先增后減,而MCI和AD組隨濃度升高逐漸增多;UPO刺激時,NC隨濃度升高POC激活體素數(shù)逐漸減少,MCI和AD組隨濃度升高依次增多�？刂颇挲g因素時,三組受試者吸入PO和UPO后,POC激活水平與MOCA評分呈正相關(guān)(r=0.277,r=0.342,P0.05),與嗅覺識別閾值評分呈負(fù)相關(guān)(r=-0.391,-0.371,P0.01);額下回眶部激活水平與MOCA評分呈正相關(guān)(r=0.227,P0.05;r=0.331,P0.05),與嗅覺識別閾值評分呈負(fù)相關(guān)(r=-0.412,r=-0.316,P0.05)。PO刺激時,三組受試者行為學(xué)變化形式無差異(χ2=5.681,P=0.058);UPO刺激時,三組受試者行為學(xué)變化形式存在差異(χ2=31.275,P=0.000)。兩兩比較發(fā)現(xiàn):NC組與MCI組(χ2=7.209,P=0.027)、NC組與AD組(χ2=23.794,P=0.000)、MCI組與AD組(χ2=15.520,P=0.000)均存在差異。結(jié)論:無論年輕組還是NC,UPO較PO激活腦區(qū)的范圍更大。NC活化的腦區(qū)范圍減小,提示隨著年齡增長嗅覺功能的減退。年輕組吸入兩種氣味時于POC區(qū)和額下回眶部激活體素數(shù)存在差異,而NC僅在額下回眶部存在差異,可能反映了嗅覺功能減退的自然進(jìn)程。與NC組相比,MCI和AD組吸入兩種氣味時ROIawo激活體素數(shù)均無差異,推測與AD病理改變累及ROIawo相關(guān)。吸入PO和UPO時額下回眶部激活體素數(shù)的差異性可以成為區(qū)分NC和MCI的生物學(xué)指標(biāo)。隨氣味濃度的增加,POC區(qū)的激活模式顯示NC組產(chǎn)生了嗅覺適應(yīng);而MCI和AD組均未產(chǎn)生。吸入UPO時POC區(qū)的激活模式能夠區(qū)分NC和MCI,可作為發(fā)現(xiàn)MCI的生物學(xué)指標(biāo)。兩種氣味嗅覺fMRI結(jié)果與嗅覺主觀評分、臨床量表均有相關(guān)性,提示吸入PO和UPO的嗅覺f MRI均可評估嗅覺障礙以及與之相關(guān)的AD臨床進(jìn)程。吸入UPO后出現(xiàn)呼吸調(diào)整的行為學(xué)改變,能夠反映與個體病情相關(guān)的嗅覺障礙的程度,為臨床評測嗅覺功能診斷早期AD提供了新方向。綜上所述,與單純PO嗅覺fMRI比較,聯(lián)合應(yīng)用PO和UPO的嗅覺fMRI更有助于MCI和AD的評估。
[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.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R445.2;R749.16

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