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題名 運用函數主成分分析於阿茲海默症之診斷
Application of functional principal component analysis to diagnosis of Alzheimer’s disease
作者 李詠玄
Lee, Yong-Shiuan
貢獻者 劉惠美
Liu, Hui-Mei
李詠玄
Lee, Yong-Shiuan
關鍵詞 阿茲海默症
函數主成分分析
遞迴類神經網路
長短期記憶類神經網路
長期追蹤資料
Alzheimer’s disease
Functional principal component analysis
Recurrent neural networks
Long short-term memory networks
Longitudinal data
日期 2022
上傳時間 1-Aug-2022 17:13:51 (UTC+8)
摘要 自二十世紀晚期對於探討阿茲海默症成因、病情發展與有效治療方式的研究大量增加。其中最重要的目標之一即為於早期診斷出阿茲海默症，也就是輕度認知障礙。診斷輕度認知障礙或阿茲海默症即是統計上的分類問題。通常阿茲海默症的相關研究資料皆為長期追蹤資料，由於資料收集的方式，使得資料多為稀疏性且不規則間隔的資料。再者，基於近年來醫學診斷工具，尤其是腦部顯影的技術進步與普及，阿茲海默症資料更常為具有高維度的資料。傳統上常用的統計分類方法對於此類資料型態有其侷限性。本研究首先將資料的變數視為只具有少數觀察值的函數，使用函數主成分分析工具來重建高維度、稀疏且不規則間隔的資料，使資料收集區間內的所有觀察時間點皆能有函數的估計值。接續再利用遞迴類神經網路中專門針對時間序列資料的長短期記憶類神經網路，來對研究對象做診斷的分類。本研究的實證結果指出在最佳情境下，此作法使用較多觀察值於訓練資料集，以及使用較多的輸入變數，能夠正確辨認出最多的早期輕度認知障礙者（十一個患者中正確辨認出五個）。顯示此法對於辨認早期的輕度認知障礙有較大的潛力。針對阿茲海默症此類醫學研究中常見的不平衡資料，未來可考慮加入重新採樣的方法或是成本考量的分類方法進一步發展優化本文所提出之程序。
Since the late 20th century, researches of Alzheimer’s disease intending to better understand the causes, the progression, and effective treatments of this disease have boosted. One of the most important purposes of these researches is to detect the disease at early stages, that is, the diagnosis of mild cognitive impairment. The diagnosis is certainly the classification problem in statistics. The research data of Alzheimer’s disease are usually longitudinal, which can be very sparse and irregularlyspaced as a result of data collection process. Additionally, the research data can also have high imensional features due to improvement in clinical neuroimaging techniques. Classical approaches for classification have limitations in using the sparse and irregular, highdimensional, longitudinal data. This study is the first to implement the tool of the functional principal component analysis to reconstruct the whole
functions of all variables during the period, and then to apply the long shortterm memory networks, a recurrent neural network designed for time series data, for classification. The empirical results show that in the bestcase scenario this method identifies 5 out of 11 MCI cases in the testing dataset while the other methods only accurately predict 0 or 1 MCI case. The results suggest that this procedure has great potential for early detection of Alzheimer’s disease. The proposed method can further be developed for imbalanced data with resampling or costsensitive classification techniques.
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描述 博士
國立政治大學
統計學系
99354501
資料來源 http://thesis.lib.nccu.edu.tw/record/#G0099354501
資料類型 thesis
dc.contributor.advisor 劉惠美zh_TW
dc.contributor.advisor Liu, Hui-Meien_US
dc.contributor.author (Authors) 李詠玄zh_TW
dc.contributor.author (Authors) Lee, Yong-Shiuanen_US
dc.creator (作者) 李詠玄zh_TW
dc.creator (作者) Lee, Yong-Shiuanen_US
dc.date (日期) 2022en_US
dc.date.accessioned 1-Aug-2022 17:13:51 (UTC+8)-
dc.date.available 1-Aug-2022 17:13:51 (UTC+8)-
dc.date.issued (上傳時間) 1-Aug-2022 17:13:51 (UTC+8)-
dc.identifier (Other Identifiers) G0099354501en_US
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/141000-
dc.description (描述) 博士zh_TW
dc.description (描述) 國立政治大學zh_TW
dc.description (描述) 統計學系zh_TW
dc.description (描述) 99354501zh_TW
dc.description.abstract (摘要) 自二十世紀晚期對於探討阿茲海默症成因、病情發展與有效治療方式的研究大量增加。其中最重要的目標之一即為於早期診斷出阿茲海默症，也就是輕度認知障礙。診斷輕度認知障礙或阿茲海默症即是統計上的分類問題。通常阿茲海默症的相關研究資料皆為長期追蹤資料，由於資料收集的方式，使得資料多為稀疏性且不規則間隔的資料。再者，基於近年來醫學診斷工具，尤其是腦部顯影的技術進步與普及，阿茲海默症資料更常為具有高維度的資料。傳統上常用的統計分類方法對於此類資料型態有其侷限性。本研究首先將資料的變數視為只具有少數觀察值的函數，使用函數主成分分析工具來重建高維度、稀疏且不規則間隔的資料，使資料收集區間內的所有觀察時間點皆能有函數的估計值。接續再利用遞迴類神經網路中專門針對時間序列資料的長短期記憶類神經網路，來對研究對象做診斷的分類。本研究的實證結果指出在最佳情境下，此作法使用較多觀察值於訓練資料集，以及使用較多的輸入變數，能夠正確辨認出最多的早期輕度認知障礙者（十一個患者中正確辨認出五個）。顯示此法對於辨認早期的輕度認知障礙有較大的潛力。針對阿茲海默症此類醫學研究中常見的不平衡資料，未來可考慮加入重新採樣的方法或是成本考量的分類方法進一步發展優化本文所提出之程序。zh_TW
dc.description.abstract (摘要) Since the late 20th century, researches of Alzheimer’s disease intending to better understand the causes, the progression, and effective treatments of this disease have boosted. One of the most important purposes of these researches is to detect the disease at early stages, that is, the diagnosis of mild cognitive impairment. The diagnosis is certainly the classification problem in statistics. The research data of Alzheimer’s disease are usually longitudinal, which can be very sparse and irregularlyspaced as a result of data collection process. Additionally, the research data can also have high imensional features due to improvement in clinical neuroimaging techniques. Classical approaches for classification have limitations in using the sparse and irregular, highdimensional, longitudinal data. This study is the first to implement the tool of the functional principal component analysis to reconstruct the whole
functions of all variables during the period, and then to apply the long shortterm memory networks, a recurrent neural network designed for time series data, for classification. The empirical results show that in the bestcase scenario this method identifies 5 out of 11 MCI cases in the testing dataset while the other methods only accurately predict 0 or 1 MCI case. The results suggest that this procedure has great potential for early detection of Alzheimer’s disease. The proposed method can further be developed for imbalanced data with resampling or costsensitive classification techniques.		en_US
dc.description.tableofcontents 誌謝 i
摘要 ii
Abstract iv
Contents vi
List of Figures viii
List of Tables xi
1 Introduction 1
1.1 Dementia 2
1.2 Alzheimer’s Disease 6
1.3 Diagnosis of Alzheimer’s Disease 7
1.4 Treatment for Alzheimer’s disease 13
1.5 Outline of The Dissertation 14
2 Related Work 15
2.1 The Mixedeffects Model 16
2.2 Linear Discriminant Analysis and Related Methods 18
2.3 Functional Principal Component Analysis 20
2.3.1 Univariate FPCA 21
2.3.2 Multivariate FPCA 24
2.3.3 Application of FPCA to Medical data 26
2.4 Classification for Longitudinal Data 27
2.4.1 Functional Data Classification 27
2.4.2 Deep Learning Models 29
3 Analysis 31
3.1 Data Description 31
3.2 Multilevel Modeling for The Scores of MMSE and ADASCog13
35
3.2.1 TwoLevel Mixed Effects Model With Demographic and Neuroimaging Variables 35
3.2.2 TwoLevel Mixed Effects Model Including Fixed Effect of Grouping by Final Status 39
3.3 Univariate Functional PCA of Midanterior
Corpus Callosum 41
3.4 Multivariate Functional PCA 49
3.4.1 Multivariate Functional PCA of Left and Right Hippocampus Volumes 49
3.4.2 Multivariate Functional PCA of Cognitive Assessment Scales and fMRI Variables 56
3.5 Classification 58
3.5.1 Classification by Flexible Discriminant Analysis and Regularized Discriminant Analysis 59
3.5.2 Classification by LSTM Using Features Reconstructed From FPCA 63
4 Discussion and Conclusions 69
Reference 71
Appendix A: Tables of the Twolevel Growth Models 94		zh_TW
dc.format.extent 4503222 bytes-
dc.format.mimetype application/pdf-
dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0099354501en_US
dc.subject (關鍵詞) 阿茲海默症zh_TW
dc.subject (關鍵詞) 函數主成分分析zh_TW
dc.subject (關鍵詞) 遞迴類神經網路zh_TW
dc.subject (關鍵詞) 長短期記憶類神經網路zh_TW
dc.subject (關鍵詞) 長期追蹤資料zh_TW
dc.subject (關鍵詞) Alzheimer’s diseaseen_US
dc.subject (關鍵詞) Functional principal component analysisen_US
dc.subject (關鍵詞) Recurrent neural networksen_US
dc.subject (關鍵詞) Long short-term memory networksen_US
dc.subject (關鍵詞) Longitudinal dataen_US
dc.title (題名) 運用函數主成分分析於阿茲海默症之診斷zh_TW
dc.title (題名) Application of functional principal component analysis to diagnosis of Alzheimer’s diseaseen_US
dc.type (資料類型) thesisen_US
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dc.identifier.doi (DOI) 10.6814/NCCU202201025en_US