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Title Page

Abstract

Contents

Chapter 1. Introduction 10

1.1. Motivation 10

1.2. Definition 11

1.2.1. Problem Definition 11

1.2.2. Terminology 13

1.3. Contributions 14

Chapter 2. Related Works 15

Chapter 3. Methods 21

3.1. Materials and Image Preprocessing 21

3.2. Differential Trajectory Model 23

3.3. Time-varying Brain Network 29

Chapter 4. Experiments 34

4.1. Differential Trajectory 34

4.1.1. Regional Cortical Thinning Patterns 34

4.1.2. Comparison with Cross-sectional and Atrophy Rate Analysis 42

4.1.3. Correlation Analysis with Neuropsychological Performances 46

4.1.4. Longitudinal Subcortical Volume Trajectory 50

4.2. Time-varying Brain Network 52

4.2.1. Longitudinal Comparison 52

4.2.2. Topological Properties 55

Chapter 5. Discussion 59

Chapter 6. Conclusions 72

Bibliography 74

List of Tables

Table 3.1: Demographic and clinical characteristics of subject groups 22

Table 4.1: Regional cortical thinning trajectory for each MCI group where... 38

Table 4.2: Regional cortical thinning trajectory within each sex where signif-... 41

Table 4.3: Trajectories in ROIs are derived that have different types of trajec-... 43

Table 4.4: Trajectories in ROIs are derived that have different types of trajec-... 45

Table 4.5: p-values of neuropsychological test scores between baseline and... 47

Table 4.6: Correlation coefficients and p-values of MCIc subjects between... 49

Table 4.7: Longitudinal subcortical volume trajectory. Blank indicates no fit... 52

List of Figures

Figure 2.1: Conceptual diagram showing the relationship between the pro-... 18

Figure 3.1: Conceptual diagrams of hypotheses in cortical thinning trajecto-... 26

Figure 4.1: Regional cortical thinning trajectory of MCIc (a) and MCInc... 35

Figure 4.2: Regional cortical thinning trajectory of MCIc (a) and MCInc (c). 39

Figure 4.3: Regional cortical thinning trajectory of females (a, c) and males... 40

Figure 4.4: Comparison to cross-sectional analysis and atrophy-rate analy-... 45

Figure 4.5: Correlational analysis with neuropsychological performances. 48

Figure 4.6: Longitudinal subcortical volume trajectories of MCIc (a) and... 51

Figure 4.7: Degree distribution with hub regions from similarity measure. 54

Figure 4.8: Network measures: Five network summary measures for MCIc... 56

Figure 4.9: Average regional specificity for the left hemisphere of MCInc... 58

Figure 5.1: Representative regions showing conflicting cortical thinning tra-... 61

Figure 5.2: Regional cortical thinning trajectory of MCIc (a,c) and MCInc... 65

초록보기

Alzheimer's disease (AD) is the most common cause of dementia in elderly pa-tients. The dynamics of the cortical thinning driven by AD are hypothesized to follow sigmoid trajectories, i.e., the rate of tissue loss first accelerates, then re-mains constant, and finally decelerates. Herein, a method is proposed to identify a trajectory model that best describes regional cortical thinning pattern over time and is applied to patients with mild cognitive impairment (MCI) to compare be-tween MCI converters (MCIc, n＝103) and non-converters (MCInc, n＝107). The left supramarginal gyrus, the bilateral medial and lateral temporal lobes, conflict-ing trajectories between groups are observed. Representative trajectories are U-shaped quadratic (decelerating pattern) in MCIc and inverted U-shaped quadratic trajectory (accelerating pattern) in MCInc, possibly reflecting a more advanced stage of neurodegeneration in MCIc. Within the 2-year study period, the cortical atrophy rate of MCIc in regions with conflicting trajectories are significantly faster than that of MCInc in year 0-1, whereas it is not significantly different in year 1-2, indicating that the cortical atrophy rate should be interpreted in the context of the overall cortical trajectories. Second, in the subcortical atrophy, the bilateral caudate and left hippocampus and right putamen have conflicting trajectories be-tween MCIc and MCInc. The trajectory analysis presents distinguishable regions with false discovery compared to previous works. Third, time-varying network is analyzed using a proposed network similarity measure based on modified Haus-dorff distance and its magnitude. Longitudinal pattern in network-level properties also differentiates MCIc from MCInc. Bilateral banks of the superior temporal sul-cus, inferior parietal and caudal middle frontal gyrus, left middle temporal, and right pars opercularis are identified as hub nodes related to AD. Time-varying network measures distinguish between MCIc and MCInc, which also verifies the hypothetical sigmoid model of disease progression. These methods may be useful in predicting the future course of patients with MCI.

참고문헌 (121건) : 자료제공( 네이버학술정보 )

참고문헌 목록에 대한 테이블로 번호, 참고문헌, 국회도서관 소장유무로 구성되어 있습니다.
번호 참고문헌 국회도서관 소장유무
1 Dynamics of gray matter loss in Alzheimer's disease. 네이버 미소장
2 Gray matter atrophy rate as a marker of disease progression in AD 네이버 미소장
3 Discriminative analysis of early-stage Alzheimer's disease and normal aging with automatic segmentation technique in subcortical gray matter structures: a multicenter in vivo MRI volumetric and DTI study. 네이버 미소장
4 Mixed brain pathologies account for most dementia cases in community-dwelling older persons. 네이버 미소장
5 Relationships between biomarkers in aging and dementia. 네이버 미소장
6 MRI and CSF biomarkers in normal, MCI, and AD subjects: diagnostic discrimination and cognitive correlations. 네이버 미소장
7 Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade 네이버 미소장
8 Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. The Lancet Neurology, 12(2):207 - 216, 2013. 미소장
9 Mild cognitive impairment: clinical characterization and outcome. 네이버 미소장
10 Progression of mild cognitive impairment to dementia in clinic- vs community-based cohorts. 네이버 미소장
11 Mild Cognitive Impairment. 네이버 미소장
12 Identification of conversion from mild cognitive impairment to Alzheimer's disease using multivariate predictors. 네이버 미소장
13 Network-level analysis of cortical thickness of the epileptic brain 네이버 미소장
14 Thinning of the cerebral cortex in aging. 네이버 미소장
15 Dementia epidemiology 네이버 미소장
16 The clinical use of structural MRI in Alzheimer disease. Neurology, 6(2):67-77. 미소장
17 Nonlinear time course of brain volume loss in cognitively normal and impaired elders 네이버 미소장
18 In vivo mapping of incremental cortical atrophy from incipient to overt Alzheimer’s disease 네이버 미소장
19 The dynamics of cortical and hippocampal atrophy in Alzheimer disease. 네이버 미소장
20 3D maps from multiple MRI illustrate changing atrophy patterns as subjects progress from mild cognitive impairment to Alzheimer's disease 네이버 미소장
21 Mild cognitive impairment 네이버 미소장
22 Longitudinal changes in cortical thickness associated with normal aging 네이버 미소장
23 Longitudinal changes in cortical thickness in autism and typical development 네이버 미소장
24 Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. 네이버 미소장
25 Regional rates of neocortical atrophy from normal aging to early Alzheimer disease. 네이버 미소장
26 Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment 네이버 미소장
27 Longitudinal MRI atrophy biomarkers: Relationship to conversion in the ADNI cohort 네이버 미소장
28 Comparison of different MRI brain atrophy rate measures with clinical disease progression in AD. 네이버 미소장
29 Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease. 네이버 미소장
30 Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration. 네이버 미소장
31 Atrophy rates accelerate in amnestic mild cognitive impairment. 네이버 미소장
32 Atrophy accelerates with conversion from mild cognitive impairment to Alzheimer disease. 네이버 미소장
33 The elusive concept of brain connectivity 네이버 미소장
34 Handbook of brain connectivity. Springer, 2007. 미소장
35 The human connectome: A structural description of the human brain. 네이버 미소장
36 Networks of the Brain. The MIT Press, 1st edition, 2010. 미소장
37 Functional and effective connectivity in neuroimaging: A synthesis 네이버 미소장
38 Neurophysiological architecture of functional magnetic resonance images of human brain. 네이버 미소장
39 Small-world anatomical networks in the human brain revealed by cortical thickness from MRI. 네이버 미소장
40 Mapping Human Whole-Brain Structural Networks with Diffusion MRI 네이버 미소장
41 Structural insights into aberrant topological patterns of large-scale cortical networks in Alzheimer's disease. 네이버 미소장
42 Canales-Rodriguez, Yasser Aleman-Gomez, and Lester Melie-Garcia. Studying the human brain anatomical network via diffusion-weighted MRI and graph theory. NeuroImage, 40(3):1064 - 1076, 2008. 미소장
43 Uncovering intrinsic modular organization of spontaneous brain activity in humans. 네이버 미소장
44 Discriminant analysis of longitudinal cortical thickness changes in Alzheimer's disease using dynamic and network features 네이버 미소장
45 A longitudinal study of structural brain network changes with normal aging. 네이버 미소장
46 Mapping the structural core of human cerebral cortex. 네이버 미소장
47 Neuroscience: Fear net 네이버 미소장
48 [Structural and functional neuronal connectivity in Alzheimer's disease: a combined DTI and fMRI study]. 네이버 미소장
49 Brain structural and functional connectivity and the progression of neuropathology in Alzheimer's disease. 네이버 미소장
50 Functional brain networks develop from a "local to distributed" organization. 네이버 미소장
51 Bullmore. Hierarchical modularity in human brain functional networks. Front Neuroinformatics, 3, 2010. 미소장
52 A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. 네이버 미소장
53 Resting-state functional connectivity as a marker of disease progression in Parkinson's disease: A longitudinal MEG study 네이버 미소장
54 Automatic classification of patients with Alzheimer's disease from structural MRI: A comparison of ten methods using the ADNI database 네이버 미소장
55 Within-subject template estimation for unbiased longitudinal image analysis. NeuroImage, 61(4):1402 - 1418, 2012. 미소장
56 Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. NeuroImage, 53(1):1 - 15, 2010. 미소장
57 An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3):968 - 980, 2006. 미소장
58 Statistical methods for research workers. Oliver & Boyd Edinburgh, 1925. 미소장
59 The design of experiments. Oliver & Boyd Edinburgh, 1935. 미소장
60 Statistical Concepts: A Second Course. Lawrence Erlbaum Associates, 2007. 미소장
61 Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing 네이버 미소장
62 Simple linear regression. Regression Analysis by Example, pages 21-51, 2006. 미소장
63 Statistical analysis of longitudinal neuroimage data with Linear Mixed Effects models 네이버 미소장
64 Spatiotemporal linear mixed effects modeling for the mass-univariate analysis of longitudinal neuroimage data 네이버 미소장
65 A guide to appropriate use of correlation coefficient in medical research. Malawi Medical Journal, 24(3):69-71, 2012. 미소장
66 Wechsler intelligence scale for children. The Psychological Corporation, 1949. 미소장
67 WISC-III : Wechsler Intelligence Scale for Children. The Psychological Corporation, 3rd edition, 1991. 미소장
68 Boston Naming Test. Philadelphia: Lea & Febiger, 1983. 미소장
69 The challenge of time: Clock-drawing and cognitive function in the elderly 네이버 미소장
70 L'examen clinique en psychologie. Presses universitaires de France, 1964. 미소장
71 The assessment of aphasia and related disorders. Philadelphia, Pa. : Lea and Febiger, 2nd ed edition, 1984. 미소장
72 Partington's pathways test. Psychological Service Center Journal, 1:11-20, 1949. 미소장
73 The measurement of adult intelligence. William & Wiklkins, Baltimore, MD, 1939. 미소장
74 A cancellation test: its reliability in assessing attentional deficits in Alzheimer's disease. 네이버 미소장
75 A composite score for executive functioning, validated in Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants with baseline mild cognitive impairment 네이버 미소장
76 Development and assessment of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 네이버 미소장
77 “Mini-mental state” 네이버 미소장
78 A new rating scale for Alzheimer's disease. 네이버 미소장
79 Stochastic relaxation, gibbs distributions, and the bayesian restoration of images. 네이버 미소장
80 Significance test for comparing complex microbial community fingerprints using pairwise similarity measures 네이버 미소장
81 Complex network measures of brain connectivity: Uses and interpretations. NeuroImage, 52(3):1059 - 1069, 2010. 미소장
82 Identification and classification of hubs in brain networks. 네이버 미소장
83 Sex differences in cortical thickness mapped in 176 healthy individuals between 7 and 87 years of age. 네이버 미소장
84 Tracking Alzheimer's Disease 네이버 미소장
85 Sex differences in thickness, and folding developments throughout the cortex 네이버 미소장
86 Model selection in linear mixed effect models. Journal of Multivariate Analysis, 109:109 - 129, 2012. 미소장
87 The Bayesian information criterion: background, derivation, and applications 네이버 미소장
88 Computational Statistics in MATLAB® 네이버 미소장
89 Brain atrophy rates predict subsequent clinical conversion in normal elderly and amnestic MCI. 네이버 미소장
90 Baseline and longitudinal patterns of brain atrophy in MCI patients, and their use in prediction of short-term conversion to AD: Results from ADNI 네이버 미소장
91 Accelerating cortical thinning: Unique to dementia or universal in aging Cerebral Cortex, 24(4):919-934, 2014. 미소장
92 Sex differences in cognitive impairment and Alzheimer's disease. Frontiers in Neuroendocrinology, 35(3):385 -403, 2014. 미소장
93 Brain sex matters: Estrogen in cognition and Alzheimer’s disease 네이버 미소장
94 Functional implications of hippocampal volume and diffusivity in mild cognitive impairment 네이버 미소장
95 Hippocampal volume and asymmetry in mild cognitive impairment and Alzheimer's disease: Meta-analyses of MRI studies. 네이버 미소장
96 Volumetric MRI study of the caudate nucleus in patients with dementia with Lewy bodies, Alzheimer's disease, and vascular dementia. 네이버 미소장
97 Caudate nucleus volumes in frontotemporal lobar degeneration: differential atrophy in subtypes. 네이버 미소장
98 3d maps localize caudate nucleus atrophy in 400 Alzheimer's disease, mild cognitive impairment, and healthy elderly subjects. Neurobiology of Aging, 31(8):1312 - 1325, 2010. 미소장
99 Strongly reduced volumes of putamen and thalamus in Alzheimer's disease: an MRI study 네이버 미소장
100 Topography of brain atrophy during normal aging and alzheimer's disease 네이버 미소장
101 Focal decline of cortical thickness in Alzheimer's disease identified by computational neuroanatomy. 네이버 미소장
102 Spatial patterns of cortical thinning in mild cognitive impairment and Alzheimer's disease 네이버 미소장
103 The cortical signature of Alzheimer's disease: regionally specific cortical thinning relates to symptom severity in very mild to mild AD dementia and is detectable in asymptomatic amyloid-positive individuals. 네이버 미소장
104 Early diagnosis of Alzheimer's disease using cortical thickness: impact of cognitive reserve 네이버 미소장
105 Individual subject classification for Alzheimer's disease based on incremental learning using a spatial frequency representation of cortical thickness data 네이버 미소장
106 Identification of Atrophy Patterns in Alzheimer's Disease Based on SVM Feature Selection and Anatomical Parcellation 네이버 미소장
107 Heterogeneous data fusion for Alzheimer's disease study. In Proceedings of the 14th ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, KDD '08, pages 1025-1033, New York, NY, USA, 2008. ACM. 미소장
108 Identifying Alzheimer's disease-related brain regions from multi-modality neuroimaging data using sparse composite linear discrimination analysis. Advances in Neural Information Processing Systems 24: 25th Annual Conference on Neural Information Processing Systems 2011, NIPS 2011, pages 808-816, 2011. 미소장
109 Predominant Left Hemisphere Metabolic Dysfunction in Dementia 네이버 미소장
110 Controversial neuropsychological issues in Alzheimer's disease 네이버 미소장
111 Cognitive functions and brain structures: A quantitative study of CSF volumes on Alzheimer patients and healthy control subjects 네이버 미소장
112 Searching for a baseline: Functional imaging and the resting human brain 네이버 미소장
113 The Brain's Default Network 네이버 미소장
114 The common neural basis of autobiographical memory, prospection, navigation, theory of mind, and the default mode: a quantitative meta-analysis. 네이버 미소장
115 Default-Mode Network Activity Distinguishes Alzheimer's Disease from Healthy Aging: Evidence from Functional MRI 네이버 미소장
116 A default mode of brain function: A brief history of an evolving idea. NeuroImage, 37(4):1083 - 1090, 2007. 미소장
117 Altered brain response for semantic knowledge in Alzheimer's disease 네이버 미소장
118 Automatic Differentiation of Anatomical Patterns in the Human Brain: Validation with Studies of Degenerative Dementias 네이버 미소장
119 A comprehensive study of gray matter loss in patients with Alzheimer’s disease using optimized voxel-based morphometry 네이버 미소장
120 Using voxel-based morphometry to map the structural changes associated with rapid conversion in MCI: A longitudinal MRI study 네이버 미소장
121 Atrophy of medial temporal lobes on MRI in ``probable'' Alzheimer's disease and normal ageing: diagnostic value and neuropsychological correlates 네이버 미소장

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