本文選題：輕度認(rèn)知障礙 + 阿爾茨海默病　； 參考：《復(fù)旦大學(xué)》2014年博士論文

【摘要】：第一部分aMCI與輕度AD基于體素的形態(tài)學(xué)MRI縱向研究目的：探討遺忘型輕度認(rèn)知障礙(amnestic-type mild cognitive impairment,aMCI)、輕度阿爾茨海默氏病(Alzheimer's disease, AD)患者相對(duì)于正常老年人灰質(zhì)體積變化特點(diǎn)。方法：采用3.0磁共振,對(duì)37例aMCI患者、30例輕度AD患者及30例正常老年人進(jìn)行三維T1WI掃描,運(yùn)用SPM8分析軟件,采用基于體素的形態(tài)學(xué)測(cè)量法(Voxel-based morphometry, VBM)對(duì)掃描獲得的結(jié)構(gòu)圖像,進(jìn)行全腦灰質(zhì)體積基于體素的統(tǒng)計(jì)學(xué)比較。其中17例aMCI患者一年后縱向隨訪。結(jié)果：與正常對(duì)照組比較,aMCI組雙側(cè)顳中、下回,海馬、海馬旁回、尾狀核、殼核、緣上回、丘腦及雙側(cè)枕葉,此外還見于左側(cè)中央后回、角回、右側(cè)島葉、中央前回及額上回灰質(zhì)萎縮,其差異具有統(tǒng)計(jì)意義。輕度AD組的雙側(cè)顳中回、額中回、額上回、枕葉梭狀回、左側(cè)中央后回、楔前葉、右側(cè)緣上回、中央前回及鰓蓋、頂上葉、側(cè)枕皮層及額下回灰質(zhì)萎縮,其差異具有統(tǒng)計(jì)意義。輕度AD組與aMCI組比較,腦灰質(zhì)萎縮區(qū)主要位于右側(cè)楔前葉及側(cè)枕皮層,左側(cè)枕下回,另還可見于雙側(cè)緣上回、額中回、左側(cè)旁扣帶回、角回、顳下回、右側(cè)殼核、額下回、顳上回、枕中回及腦干(P0.05, FDR-corrected, Cluster100體素)�？v向隨訪中,雙側(cè)額顳頂枕葉進(jìn)一步萎縮(P0.05, uncorrected, Cluster100體素)。結(jié)論：通過基于體素的形態(tài)學(xué)研究能夠發(fā)現(xiàn)aMCI期及輕度AD患者腦灰質(zhì)細(xì)微結(jié)構(gòu)的萎縮,從而在疾病的早期提供診斷支持,為盡早的干預(yù)治療提供幫助。第二部分aMCI與輕度AD基于體素的形態(tài)學(xué)腦PASL縱向研究目的：應(yīng)用脈沖動(dòng)脈自旋標(biāo)記(pulsed arterial spin labeling, PASL)技術(shù)、探討aMCI、輕度AD患者腦血流灌注的變化特點(diǎn)。方法：采用3.0磁共振,采集靜息狀態(tài)下37例aMCI患者、30例輕度AD患者及30例正常老年人動(dòng)脈自旋標(biāo)記的灌注成像數(shù)據(jù),計(jì)算其相對(duì)腦血流量。其中17例aMCI患者一年后縱向隨訪。結(jié)果：與正常對(duì)照組比較,aMCI組雙側(cè)后扣帶回及楔前葉血流增加,其差異具有統(tǒng)計(jì)意義。輕度AD組的左側(cè)頂上下回、角回、額中回及右側(cè)顳上回血流減低,其差異具有統(tǒng)計(jì)意義((Alphasim corrected,p0.05,最小cluster體積k=1632體素)�？v向隨訪中,雙側(cè)額顳頂枕葉、丘腦、扣帶回均有血流灌注增加及減低的改變,血流增加略多,尤其是額葉(p0.05,uncorrected,k≥100體素)結(jié)論：動(dòng)脈自旋標(biāo)記的灌注成像為檢測(cè)MCI及AD患者異常灌注改變提供了一種有價(jià)值的方法,MCI組與AD組患者的灌注異常與其腦結(jié)構(gòu)和功能的改變密切相關(guān)。第三部分aMCI與輕度AD基于體素的全腦DTI縱向研究目的：應(yīng)用磁共振彌散張量成像(Diffusion tensor imaging, DTI)技術(shù)、探討aMCI、輕度AD患者腦白質(zhì)微觀結(jié)構(gòu)的變化特點(diǎn)。方法：采用3.0磁共振,對(duì)37例aMCI患者、30例輕度AD患者及30例正常老年人進(jìn)行DTI檢查,運(yùn)用基于纖維束的空間統(tǒng)計(jì)(Tract-basedspatial statistics,TBSS)軟件以比較白質(zhì)結(jié)構(gòu)的差異。17例aMCI患者一年后縱向隨訪。結(jié)果：與正常對(duì)照組比較,aMCI組右側(cè)胼胝體膝部,雙側(cè)下額枕束、上縱束、右側(cè)的內(nèi)囊前肢、前丘腦放射及左側(cè)下縱束的腦白質(zhì)FA值減低；FA值增高區(qū)大部分位于右側(cè)的皮質(zhì)脊髓束、前丘腦放射,其次是于右側(cè)上縱束、扣帶束及其海馬部分,另外還見于雙側(cè)下額枕束、右側(cè)前丘腦放射、右側(cè)胼胝體輻射線枕部及左側(cè)上縱束。腦白質(zhì)MD增加區(qū)主要位于左側(cè)半球,集中于左側(cè)下縱束、鉤狀束、下額枕束、上縱束及上縱束顳部、皮質(zhì)脊髓束、右側(cè)上縱束及上縱束顳部及鉤狀束。腦白質(zhì)MD減低區(qū)見于小部分右側(cè)皮質(zhì)脊髓束,其差異具有統(tǒng)計(jì)意義(P0.05,t值2-6,Corrected)。輕度AD組的左側(cè)上放射冠、左側(cè)上縱束、雙側(cè)下額枕束、右側(cè)扣帶束的海馬部、外囊以及穹隆、左側(cè)前丘腦放射、穹隆、終紋、外囊、扣帶束腦白質(zhì)FA值減低;FA增高區(qū)大部分位于左側(cè)皮質(zhì)脊髓束、前丘腦放射、右側(cè)上縱束,還可見于右側(cè)鉤形束、扣帶束及其海馬區(qū)、下額枕束、右側(cè)前丘腦放射、右側(cè)胼胝體輻射線枕部、雙側(cè)下縱束、左側(cè)扣帶束。腦白質(zhì)MD增加區(qū)體素明顯增大,主要位于左側(cè)半球,集中在左側(cè)上縱束、皮質(zhì)脊髓束以及右側(cè)皮質(zhì)脊髓束的小部分。腦白質(zhì)MD減低區(qū)見于小部分右側(cè)皮質(zhì)脊髓束。其差異具有統(tǒng)計(jì)意義(P0.05,t值2-6；Corrected)�？v向隨訪中,腦白質(zhì)FA值降低明顯,集中在左側(cè)上放射冠及下縱束,少許右側(cè)扣帶束及上縱束FA值增高。MD增高明顯,以左側(cè)枕鉗及右側(cè)扣帶束為主,少許右側(cè)扣帶束及上縱束MD減低。(P0.05, uncorrected, Cluster100體素)結(jié)論：DTI能夠觀察AD白質(zhì)微觀結(jié)構(gòu)的變化,這些變化可以成為診斷疾病的生物學(xué)標(biāo)記物。第四部分aMCI與輕度AD的靜息態(tài)fMRI縱向研究目的：聯(lián)合應(yīng)用低頻波振幅分析(Amplitude of Low Frequency Fluctuation, ALFF)和種子點(diǎn)相關(guān)分析(seed-basedcorrelation analysis),探討aMCI、輕度AD患者靜息態(tài)腦功能連接的變化特點(diǎn)。方法：采用3.0磁共振,對(duì)37例aMCI患者、30例輕度AD患者及30例正常老年人,進(jìn)行靜息態(tài)fMRI掃描。利用SPM8軟件對(duì)于所有數(shù)據(jù)進(jìn)行預(yù)處理,用REST及DPARSF軟件進(jìn)行低頻波振幅分析,比較病患組與正常組具有顯著差異的腦區(qū),提取該腦區(qū)的峰值點(diǎn)作為種子點(diǎn),以4mm為半徑做全腦功能連接,提取種子點(diǎn)做Pearson分析。結(jié)果：與正常對(duì)照組比較,aMCI組ALFF增高區(qū)位于右側(cè)額上中回；ALFF降低區(qū)位于右側(cè)額中回、左側(cè)楔前葉。輕度AD組的ALFF增高區(qū)位于右側(cè)胼胝體,左側(cè)前運(yùn)動(dòng)皮層、額上回,ALFF降低區(qū)位于右側(cè)直回,左側(cè)扣帶回、后扣帶回、楔前葉,其差異具有統(tǒng)計(jì)意義。輕度AD組與aMCI組比較,ALFF曾高區(qū)位于右側(cè)輔助運(yùn)動(dòng)區(qū)及額葉,左側(cè)中央前回、中央旁小葉、扣帶回、輔助運(yùn)動(dòng)區(qū),還見于右側(cè)中央前回、額上回,左側(cè)中央后回；ALFF降低區(qū)位于雙側(cè)小腦、左側(cè)額下回、枕上回、枕中回(P0.01,uncorrected,K≥10體素)。aMCI組的默認(rèn)網(wǎng)絡(luò)功能連接強(qiáng)度增高區(qū)位于雙側(cè)楔前葉,中央扣帶回；減低區(qū)位于右側(cè)顳葉。輕度AD組的默認(rèn)網(wǎng)絡(luò)功能連接強(qiáng)度增高區(qū)位于左側(cè)島葉,左額下回眶部；減低區(qū)位于雙側(cè)額葉,顳中回。輕度AD組與aMCI組比較,與默認(rèn)網(wǎng)絡(luò)功能連接強(qiáng)度增高區(qū)位于右額上回,減低區(qū)位于右額葉、前扣帶回、中央扣帶回、顳葉、緣上回,右額下回三角部、中央旁小葉(P0.01, uncorrected,體素)。17例aMCI病例一年后隨訪,右枕葉及距狀皮層ALFF波幅減低(P0.05, FWE corrected,,K≥10體素)；右側(cè)小腦默認(rèn)網(wǎng)絡(luò)連接強(qiáng)度下降,右側(cè)頂下小葉、角回、額上回、額中回、左側(cè)頂下小葉、顳下回、額中回連接強(qiáng)度增高(P0.01, uncorrected,K≥10體素)。結(jié)論：通過種子點(diǎn)相關(guān)分析可以在aMCI、輕度AD患者腦結(jié)構(gòu)出現(xiàn)異常前發(fā)現(xiàn)靜息態(tài)腦功能網(wǎng)絡(luò)的特異性改變。
[Abstract]:Part one aMCI and light AD based on voxel based morphological MRI longitudinal study objective: To explore the characteristics of gray volume changes in patients with amnestic mild cognitive impairment (amnestic-type mild cognitive impairment, aMCI), mild Alzheimer's disease (Alzheimer's disease, AD) relative to normal elderly people. Method: 3 MRI, 37 cases of a MCI patients, 30 patients with mild AD and 30 normal aged people were scanned by three dimensional T1WI, using SPM8 analysis software, using the Morphin based morphometry (Voxel-based morphometry, VBM) to compare the scanned structural images of the whole brain, and 17 cases of aMCI patients were followed up one year later. Fruit: compared with the normal control group, the aMCI group had bilateral temporal, lower gyrus, hippocampus, parahippocampal gyrus, caudate nucleus, putamen, marginal gyrus, thalamus and bilateral occipital lobe, in addition to the left central posterior gyrus, the angular gyrus, the right Island leaf, the anterior central gyrus and the upper back of the frontal gyrus, with statistical significance. The bilateral temporal gyrus, the middle frontal gyrus, the upper frontal gyrus, the occipital of the mild AD group. The leaf spindle gyrus, the left central posterior gyrus, the anterior central lobe, the right margin of the upper gyrus, the anterior central gyrus and the gill cover, the upper lobe, the lateral occipital cortex and the lower frontal gyrus were atrophied, and the difference was statistically significant. The mild AD group was mainly located in the right anterior and lateral occipital cortex, the left occipital cortex, the left occipital gyrus, and the upper margin of the bilateral margin. Gyrus, lateral cingulate gyrus, angular gyrus, inferior temporal gyrus, right putamen, inferior frontal gyrus, upper temporal gyrus, occipital gyrus and brainstem (P0.05, FDR-corrected, Cluster100 voxel). Bilateral frontal and temporal occipital lobes were further atrophied (P0.05, uncorrected, Cluster100 voxel) during longitudinal follow-up. Conclusion: aMCI and mild AD can be found through morphological study based on voxel. The atrophy of the fine structure of the cerebral gray matter in the patient, thus providing diagnostic support in the early stage of the disease, and providing help for early intervention. Second part aMCI and the mild AD based Morphin based morphological brain PASL longitudinal study: the use of pulsed arterial spin labeling, PASL technology to explore the brain of aMCI, mild AD. Methods: 3 magnetic resonance imaging (3 MRI) were used to collect the perfusion imaging data of 37 patients with aMCI, 30 mild AD patients and 30 normal elderly patients with arterial spin labeling, and 17 cases of aMCI patients were followed up for one year after a year. The results were compared with the normal control group, and the bilateral posterior buckle in the aMCI group. The difference in the left top and lower gyrus of the mild AD group, the angular gyrus, the middle frontal gyrus and the right temporal gyrus were decreased, and the difference was statistically significant (Alphasim corrected, P0.05, the minimum cluster volume k=1632 voxel). In the longitudinal follow-up, the bilateral frontal and temporal occipital lobes, thalamus, cingulate gyrus had blood perfusion. The increase and reduction of blood flow increased slightly, especially in the frontal lobes (P0.05, uncorrected, k > 100 voxins) conclusion: arterial spin labeling perfusion imaging provides a valuable method for detecting abnormal perfusion changes in MCI and AD patients. The perfusion anomaly in group MCI and AD patients is closely related to changes in the structure and function of the brain. Third AMCI and mild AD based on voxel based whole brain DTI longitudinal study objective: To explore the change characteristics of white matter microstructure in aMCI and mild AD patients by magnetic resonance diffusion tensor imaging (DTI) technique. Methods: 3 MRI were used in 37 cases of aMCI, 30 mild AD and 30 normal elderly. Tract-basedspatial Statistics (TBSS) software based on fiber bundle to compare the difference of white matter structure in.17 cases, aMCI patients were followed up for one year. Results: compared with the normal control group, the right corpus callosum, bilateral inferior occipital fasciculus, upper longitudinal fasciculus, right inner capsule forelimb, anterior thalamus radiation and left longitudinal fasciculus were compared with the normal control group. The FA value of cerebral white matter decreased, most of the higher FA value was located in the right lateral corticospinal tract and anterior thalamus, followed by the right superior longitudinal fascicle, the cingulate bundle and the hippocampus, and the bilateral inferior occipital bundle, the right anterior thalamus, the right corpus callosum occipital and the left superior longitudinal bundle. The brain white matter MD area was mainly located in the left half of the hemisphere. The ball was concentrated on the left inferior longitudinal fasciculus, the hook shaped bundle, the lower occipital bundle, the upper longitudinal beam and the temporal and longitudinal fasciculus, the corticospinal tract, the right superior longitudinal fascicle, the upper longitudinal fascicle and the hook shaped bundle. The MD reduction area of the white matter was found in the small part of the right corticospinal tract. The difference was statistically significant (P0.05, t 2-6, Corrected). The left upper radiate crown of the mild AD group and the left upper longitudinal longitudinal section were in the mild AD group. Bundles, bilateral inferior occipital fasciculus, right cingulate hippocampal, outer capsule and dome, radiating in the left anterior thalamus, dome, terminal striate, outer capsule, and cingulate bundle of brain white matter FA value decreased; most of the FA increased area was located in the left corticospinal tract, anterior thalamus radiating, right superior longitudinal fascicles, also seen in the right hook bundle, cingulate bundle and hippocampus, inferior occipital fasciculus, right front Radiation of the thalamus, the occipital of the right corpus callosum radiation line, bilateral inferior longitudinal fasciculus, and the left cingulate bundle. The voxel in the MD area of the cerebral white matter increased obviously, mainly in the left hemisphere, concentrated in the left superior longitudinal tract, the corticospinal tract and the right corticospinal tract. The MD reduction area of the white matter was seen in the small part of the right corticospinal tract. The difference was statistically significant. Significance (P0.05, t value 2-6; Corrected). In longitudinal follow-up, the FA value of white matter decreased obviously, concentrated in the left upper and lower longitudinal fascicles, a little right cingulate bundle and the FA value of upper longitudinal bundle increased obviously, with the left occipital forceps and the right cingulate bundle mainly, and a little right cingulate bundle and the upper longitudinal bundle MD decreased. (P0.05, uncorrected, Cluster100 voxel). Conclusion: DTI can observe the changes in the microstructure of AD white matter. These changes can be a biological marker for diagnosis of disease. Fourth part aMCI and the resting state fMRI longitudinal study of mild AD: Combined Application of low frequency wave amplitude analysis (Amplitude of Low Frequency Fluctuation, ALFF) and seed point correlation analysis (seed-basedcorrelati) On analysis), to explore the change characteristics of resting state brain function connection in aMCI and mild AD patients. Methods: 3 magnetic resonance (MRI) was used to perform resting state fMRI scan in 37 cases of aMCI, 30 cases of mild AD and 30 normal old people. All data were pretreated with SPM8 software, and the amplitude analysis of low frequency wave was carried out by REST and DPARSF software. Compared with the normal group, the brain area was significantly different from that of the normal group, and the peak point of the brain area was extracted as the seed point. 4mm was used as the radius to do the whole brain function connection and the seed point was extracted for Pearson analysis. Results: compared with the normal control group, the higher ALFF area in the aMCI group was located in the right upper middle frontal gyrus, the lower ALFF area was located in the right frontal gyrus, and the left left anterior lobe was light. The increased area of ALFF in the AD group was located in the right corpus callosum, the left anterior motor cortex, the upper frontal gyrus, the lower ALFF area located in the right direct gyrus, the left cingulate gyrus, the posterior cingulate gyrus, and the anterior wedge of the wedge. Compared with the aMCI group, the mild AD was located in the right auxiliary movement area and frontal lobe, the left central anterior gyrus, paraclal lobule, cingulate gyrus. The auxiliary motor area is also seen in the right anterior central gyrus, the upper frontal gyrus, and the left posterior central gyrus, and the ALFF area is located in the bilateral cerebellum, the left inferior frontal gyrus, the upper occipital gyrus, the middle occipital gyrus (P0.01, uncorrected, K > 10 voxel), which is located in the anterior lobe of the wedge, the central cingulate gyrus, and the lower part of the right temporal lobe. The defaults in the AD group were located in the left Island lobe and the left inferior frontal gyrus, in the left frontal lobe, in the left inferior frontal gyrus, in the bilateral frontal lobe, in the middle temporal gyrus, and in the mild AD group compared with the aMCI group, and the area in the right upper frontal gyrus with the default network function, the lower area in the right frontal lobe, the anterior cingulate gyrus, the central cingulate gyrus, the temporal lobe, the upper margin, right frontal gyrus. The triangle, P0.01, uncorrected, voxel,.17 cases of aMCI cases were followed up one year later. The ALFF wave amplitude of right occipital lobe and cortex was decreased (P0.05, FWE corrected, K > 10 voxin); right cerebellum defaults, right apical lobule, angular gyrus, upper frontal gyrus, upper and lower lobule, inferior temporal gyrus, and middle frontal gyrus. Du Zenggao (P0.01, uncorrected, K > 10 voxin). Conclusion: the specific changes in the resting state brain function network can be found before the abnormal brain structure of mild AD patients through the seed point correlation analysis.

【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R445.2;R749.16

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