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研究生:張峻源
研究生(外文):Chun-Yuan Chang
論文名稱:慢性腎臟病人認知功能缺損與海馬迴萎縮之關聯研究
論文名稱(外文):The Association of Cognitive Impairment and Hippocampal Atrophy in Chronic Kidney Disease
指導教授:林發暄
指導教授(外文):Fa-Hsuan Lin
口試委員:傅中玲張楊全郭文瑞吳文超
口試委員(外文):Jong-Ling FuhYang-Chyuan ChangWen-Jui KuoWen-Chau Wu
口試日期:2018-04-13
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文出版年:2018
畢業學年度:106
語文別:英文
論文頁數:33
中文關鍵詞:慢性腎臟病心血管疾病認知核磁共振影像灰質體積海馬迴皮質厚度
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長久以來慢性腎臟病人的認知功能缺損已經廣為注意,也有不少文獻提及,但是腦部結構變化以及認知表現和腎臟功能的關聯則很少被提及,到本論文旨在探討這三者之間的關聯性。本研究共納入了性別年齡相似的慢性腎臟病人(CKD)實驗組及正常腎功能對照組,每位受試者皆有接受腎功能檢查、完整的神經心知功能評估以及腦部核磁共振檢查(MRI),腦部影像資料藉由軟體FreeSurfer分析可以獲得腦部結構的各項參數,並藉此與臨床腎功能與心智功能量表進行統計分析,結果發現相較於對照組,實驗組(CKD)有較低的簡單心智功能評估分數(Mini-Mental State Examination, MMSE),較小的腦部灰質體積、海馬迴大小及皮質厚度。而估算腎絲球過濾率(eGFR)則與前述四項有明顯相關性,進一步校正干擾因子(confounding factors)線性分析發現,eGFR對於認知功能、灰質體積及皮質厚度有明顯負相關。結論在本研究中發現腎功能缺損在心智認知功能以及大腦結構之灰質體積,海馬迴體積以及皮質厚度有明顯相關。
Cognition impairment is well known in patients with chronic kidney disease (CKD). The relationship between brain structure and cognitive performance in CKD patients is still under investigation. The study aims to quantitatively assessment the relationship between brain structure and cognitive performance in patients with CKD.
39 patients with CKD and 39 age- and sex-matched control participants are recruited from a tertiary medical center. All participants underwent 3-T MRI scan neuropsychological assessments, and renal function tests. FreeSurfer software was used for imaging processing and analysis, including measurement of cortical thickness and gray matter (GM) and white matter volumes. As a result, compared with control subjects (73.1 ± 7.5 years old), patients with CKD (76.4 ± 8.4 years old) had significantly lower scores on the Mini-Mental State Examination, and forward digit span test (p < 0.01). Patients with CKD had smaller cerebral GM volume, hippocampus and decreased cortical thickness (p < 0.01) relative to the control group. Estimated glomerular filtration rate (eGFR) was correlated with cognitive performance, cortical thickness, GM volume, and hippocampal volume (p < 0.001). Linear regression analysis revealed that eGFR and GM volume were independently negatively associated with cognitive performance (p < 0.001), while eGFR and age were negatively associated with cortical thinning and GM volume after controlling for confounding factors. In conclusion, this study demonstrated that impaired kidney function is associated not only with poor cognitive performance, but also with small cerebral GM volume and reduced cortical thickness.
TABLE OF CONTENTS
序言 I
摘要 III
ABSTRACT IV
LIST OF FIGURES VII
LIST OF TABLES VIII
1. INTRODUCTION 1
2. METHODS 2
2.1 PARTICIPANTS 2
2.2 DATA COLLECTION AND ASSESSMENTS 4
2.2.1 Neuropsychological tests 4
2.2.2 MRI data acquisition & Imaging processing 5
2.2.3 Statistical analysis 8
3. RESULTS 9
3.1 CHARACTERISTICS OF THE STUDY POPULATION 9
3.2 RESULTS OF NEUROPSYCHOLOGICAL TESTING 11
3.3 HIPPOCAMPUS, GRAY MATTER VOLUME AND CORTICAL THICKNESS 13
3.4 CORRELATION ANALYSIS OF RENAL FUNCTION , COGNITION AND BRAIN MEASUREMENT 16
4. DISCUSSION 19
5. CONCLUSION 25
6. REFERENCE 27
7. APPENDIX 32

LIST OF FIGURES
FIGURE 1 THE AVERAGE BRAIN VOLUME IMAGE OF CONTROL SUBJECTS IS SHOWN ON A(CORONAL VIEW) AND B(AXIAL VIEW) WHEREAS THE BRAIN AVERAGE VOLUME IMAGE OF PATIENTS WITH CKD IS SHOWN ON C AND D. RED ARROW INDICATES THE HIPPOCAMPUS WHICH IS LOCATED ACCORDING TO TALAIRACH COORDINATES. DILATED VENTRICLE AND PERISYLVIAN SPACE AND REDUCED HIPPOCAMPAL VOLUME ARE NOTED IN CKD GROUP 14
FIGURE 2 MAPS IDENTIFYING REGIONS OF LESSER CORTICAL THICKNESS (HIGHLIGHTED) IN PATIENTS WITH CKD RELATIVE TO CONTROL SUBJECT 15
FIGURE 3 CORRELATIONS AMONG EGFR, GRAY MATTER VOLUME, AND MMSE SCORE 17


LIST OF TABLES
TABLE 1 DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF THE STUDY POPULATION 9
TABLE 2 NEUROPSYCHOLOGICAL TEST SCORES AND WHITE MATTER AND GRAY MATTER PARAMETERS 11
TABLE 3 ESTIMATES OF MULTIPLE LINEAR REGRESSION MODELS WITH NEUROPSYCHOLOGICAL TEST SCORES AND BRAIN VOLUME PARAMETERS AS DEPENDENT VARIABLES AND AGE, EDUCATION AND CKD AS INDEPENDENT VARIABLES, SHOWING EFFECTS BY STANDARDIZED COEFFICIENTS (BETA VALUE) 12
TABLE 4 RESULTS OF MULTIPLE LINEAR REGRESSION ANALYZING RENAL FUNCTION AND AGE AS PREDICTORS OF BRAIN STRUCTURE 18
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