臺灣博碩士論文加值系統

主觀記憶抱怨為個人抱怨記憶功能減退但在客觀認知功能表現正常，與阿茲海默症的病理變化與罹病風險有潛在的關聯性。感覺門控反映大腦自動對重複刺激所誘發的神經反應加以抑制的能力，用以濾除多餘的感覺訊息、維持認知表現。輕度認知障礙與阿茲海默症個案於此項能力有所受損，但未有研究探討主觀記憶抱怨者於感覺門控的表現。控制組與主觀記憶抱怨組各有19位個案，每位個案50歲以上，於客觀認知功能評估之表現均正常。主觀記憶抱怨個案其自覺記憶力衰退的情形需有他人認同。M50與M100感覺門控由paired-click paradigm量測，並使用腦磁圖儀記錄，感興趣的腦區為雙側的顳上迴、顳中回、額下廻與頂下葉。抑制程度指標為門控比值(gating ratio)，由第二個神經反應振幅除以第一個反應振幅而得，比值越大，門控表現越差。Two-way ANOVA結果指出，主觀記憶抱怨個案於頂下葉的M50門控表現顯著較控制組差，且ROC曲線分析顯示右頂下葉的M50門控可以有效的區辨兩組，反映其濾除訊息的能力受損，可能於頂下葉出現病理變化。此外，並未在兩組發現「較好的M50門控有較好的認知表現」此項關聯性。

Background：Subjective memory complaint (SMC) refers to the self-perception of subtle, persistent memory decline with intact cognitive performance. Evidence has indicated SMC possibly reflects brain changes linked to Alzheimer's disease (AD) and is seen as a risk factor for incident AD. Sensory gating (SG), referring to the automatic inhibition of neural response to the second identical stimulus, is essential to prevent redundant information from reaching higher cortical centers and optimize cognitive processing. Although studies showed AD and mild cognitive impairment presented deficient automatic inhibition, few studies explore this neurophysiological function in SMC population.
Methods：19 controls and 19 SMC subjects (All subjects ≥ 50 years) were recruited in the present study. SMC participants had memory complaints confirmed by their informants. SG of M50 and M100 components were measured by auditory paired-click paradigm via magnetoencephalographic recordings and calculated by the amplitude ratio of response to the second click over that to the first click. A higher ratio indicates worse SG ability. Two-way ANOVA (group x hemisphere) was used to compare group difference of SG in bilateral superior temporal gyrus, middle temporal gyrus, inferior frontal gyrus and inferior parietal lobule (IPL). SG components with significant group differences were involved in additional analyses described below. First, SG components with acceptable discriminative capacity were identified by receiver operating characteristic curve analysis. Second, Pearson's r was used to examine the correlations between SG and cognitive tests requiring inhibitory control.
Results：M50 SG ratio in IPL was significantly higher in SMC than control group (p = 0.014). Additionally, M50 SG ratio in the right IPL showed acceptable discriminative capacity. Furthermore, no correlations between better SG and better cognition were found.
Conclusion：Asymptomatic SMC subjects presented deficiency of filtering irrelevant information and might be accompanied by AD-related pathological changes in IPL. Particularly, M50 SG ratios in right IPL yielded the acceptable discriminative ability to distinguish between the presence and absence of SMC in the elderly with intact cognition.

Recommendation Letter from the Thesis Advisor ...
Thesis/Dissertation Oral Defense Committee Certification ...
Acknowledgments...iii
Chinese Abstract...iv
English Abstract...v
Table of contents...vi
List of figures...viii
List of Tables...ix
Chapter 1 Introduction ...1
1.1 Background ...1
1.2 Motivation and purpose ...8

Chapter 2 Literature Review ...10
2.1 Preclinical stage of Alzheimer's disease (AD) ...10
2.1.1 Introduction of preclinical stage of AD ...10
2.1.2 Pathophysiological process at the preclinical stage of AD...11
2.1.3 Subjective cognitive decline and memory complaint (SMC) ...15
2.1.4 Association between SMC and AD pathology...17
2.2 Central auditory processing (CAP)...20
2.2.1 Introduction of CAP...20
2.2.2 Auditory evoked potentials and auditory evoked fields ...22
2.3 Sensory gating (SG) ...26
2.3.1 Introduction of SG ...26
2.3.2 Cortical generators underlying SG ...28
2.3.3 Correlations between SG and cognition ...29
2.4 Specific aims and hypotheses ...31

Chapter 3 Methods ...32
3.1 Participants ...32
3.2 Assessment ...34
3.3 General Procedures and Paired-click paradigm ...36
3.4 Magnetoencephalography recordings and preprocessing ...38
3.5 MEG data analysis ...40
3.6 Statistical analysis ...43

Chapter 4 Results ...45
4.1 Demographic and neuropsychological characteristics ...45
4.2 Source distribution ...46
4.3 The differences of SG ratio between control and SMC group ...47
4.4 The discrimination capacity of M50 SG ratios in the parietal lobe ...51
4.5 The correlations between M50 SG in IPL and cognition ...52

Chapter 5 Discussion ...53

Chapter 6 Conclusion ...63

References ...64


List of figures

Figure 2.1 Updated staging framework for the preclinical (Adapted from Sperling et al, 2011 with updates from Jack et al., 2012) ...11

Figure 2.2 The curves with different colors indicate respective changes of five biological markers in the course of AD progression (Adapt from the website of Alzheimer’s Disease Neuroimaging Initiative: http://adni.loni.usc.edu/study-design/ background-rationale/) ...14

Figure 2.3 Illustration of AEP components across the timeframe ...25

Figure 2.4 Diagrammatic representation of paired-click paradigm and corresponding neural responses of P50 and N100 components ...27

Figure 3.1 Illustration of MEG data acquisition, preprocessing, and analysis...42

Figure 4.1 Grand average AEFs and corresponding cortical source maps evoked by first and second auditory stimuli in control and SMC groups ...47

Figure 4.2 Source activity of M50 and M100 components to first and second stimuli in the identified regions of interest ...49

Figure 4.3 Mean M50 and M100 SG ratio of control and SMC groups in the bilateral superior temporal gyrus, middle temporal gyrus, inferior frontal gyrus, and inferior parietal lobule ...50

Figure 4.4 The sensitivity and specificity of M50 SG in the right IPL were analyzed by ROC curve in total study subjects ...51


List of tables

Tables 4.1 Demographic and neuropsychological variables ...45

Tables 4.2 Effect of group and hemisphere on SG ratio among specific brain regions...50

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