隨著人類平均壽命逐漸增加的同時，阿茲海默失智症患者數量也逐年增加，不論在醫療支出以及照顧資源，都帶來莫大的壓力。阿茲
海默失智症患者隨著疾病惡化，常常會失去自我進食的能力，遺憾的是，即使改成管灌飲食也無法增加患者的存活時間。目前針對阿茲海默失智症的非藥物治療著重在認知功能的復健，其中包括光照治療，調控阿茲海默失智症患者的精神行為異常。2016年的研究發現給予40Hz LED閃光刺激可以促進小鼠大腦microglia吞噬類澱粉蛋白以及神經纖維纏結。
因此我們設計並製作出只要受試者主動進食就會回饋喜愛樂曲的智慧餐盒，訓練阿茲海默失智症患者自我進食，並且在受試者使用餐盒時，發出40 Hz的LED閃爍白光，利用平易近人的人機介面，同步完成進食訓練以及阿茲海默失智症非藥物治療。本實驗收案10名受試者，使用智慧餐盒8週，並且接受實驗前以及實驗後的神經認知功能測驗，我們發現經常使用餐盒的受試者在認知功能障礙篩檢量表(Cognitive abilities screening instrument, CASI)有明顯進步趨勢。未來仍需要進一步實驗找出最有效的閃光頻率、閃光照度、使用時間以及增加收案量，以創造更適合阿茲海默失智症患者的智慧餐盒，並且研究閃光刺激如何調控大腦microglia吞噬類澱粉蛋白以及適時停止microglia的過度活化。

Population of Alzheimer’s disease grows with aging society, which increases burdens of medical care, finance, and care givers. Along with disease deterioration, patients lose ability of eating by themselves. Studies showed that tube feeding could not extend life of Alzheimer’s patients. Bright light therapy is effective in augmentation of behavioral and psychiatric symptoms of dementia. Study in 2016 revealed that 1 hour of 40 Hz LED flicker enhanced microglia engulfment of amyloid and neurofibrillary tangles in mice brain.
Therefore, we designed and created a smart lunchbox which trains Alzheimer’s participants self-feeding with beloved music and gives off 40 Hz LED white light concurrently as non-pharmacological treatment of Alzheimer’s disease. After 8 weeks of trial, we found participants who use smart lunch box frequently had trend of improvement in cognitive abilities screening instrument (CASI) score. In the future, we would try to find the most effective frequency of gamma flicker, most appropriate lux of light, most effective usage time, and enroll more participants to optimize smart lunchbox. We also expect to investigate how to manipulate microglia with light flicker and maintain homeostasis of overactivated microglia in Alzheimer’s disease.

目錄
中文摘要................................................................................................................................... 8
Abstract.................................................................................................................................... 9
縮寫 Abbreviations............................................................................................................... 10
第一章 背景與文獻回顧.................................................................................................... 11
1.1 阿茲海默失智症的飲食難題................................................................................... 11
1.2 光線刺激與聲音刺激作為失智症非藥物治療 ....................................................... 11
1.3 過去已發表的阿茲海默失智症人機介面(human machine interface)研究 ............ 13
1.4 設計智慧餐盒作為阿茲海默失智症非藥物治療 ................................................... 13
第二章 材料方法................................................................................................................... 14
2.1 阿茲海默失智症受試者收案................................................................................... 14
2.2 設計與製作智慧餐盒............................................................................................... 15
2.2.1 第一版設計.................................................................................................... 15
Figure 01 ................................................................................................................. 16
Figure 02 ................................................................................................................. 16
2.2.2 第二版設計.................................................................................................... 17
Figure 03 ................................................................................................................. 18
Table 01................................................................................................................... 18
Figure 04 ................................................................................................................. 19
Figure 05 ................................................................................................................. 20
1
Figure 06 ................................................................................................................. 20
Figure 07 ................................................................................................................. 21
2.3 使用智慧餐盒........................................................................................................... 21
2.4 神經心理測驗........................................................................................................... 21
2.4.1 認知功能障礙篩檢量表 CASI...................................................................... 22
2.4.2 魏氏成人智力量表第四版次測驗--圖案完成 WAIS-IV Picture completion
................................................................................................................................. 23
2.4.3 魏氏記憶量表第三版--空間記憶廣度測驗 WMS-III spatial span.............. 23
2.4.4 類別流暢度測驗--動物 Category fluency of animal..................................... 24
2.4.5 類別流暢度測驗—水果 Category fluency of fruit ....................................... 24
2.4.6 簡短智能施測 MMSE ................................................................................... 24
2.4.7 臨床失智評估量表 CDR............................................................................... 25
2.4.8 臨床失智評估量表--分數總和 CDR-SOB ................................................... 25
2.4.9 神經精神評估量表--總分 Total NPI score ................................................... 25
2.5 使用餐盒後問卷....................................................................................................... 26
2.5.1 受試者的回饋................................................................................................ 26
Table 02................................................................................................................... 26
2.5.2 主要陪伴者的回饋........................................................................................ 26
Table 03................................................................................................................... 26
2.6 統計分析方法........................................................................................................... 27
第三章 實驗結果................................................................................................................... 28
3.1 收案流程圖............................................................................................................... 28
3.2 人體試驗委員會審核通過....................................................................................... 29
3.3 收案受試者基本特徵............................................................................................... 29
Table 04................................................................................................................... 30
2
3.4[全部受試者]餐盒使用前、使用後的認知功能測驗變化...................................... 30
Table 05................................................................................................................... 30
3.4.1[全部受試者]CASI 變化 ................................................................................ 31
Table 06................................................................................................................... 31
Figure 08 ................................................................................................................. 32
3.4.2[全部受試者]WAIS-IV Picture completion 變化........................................... 32
Table 07................................................................................................................... 33
Figure 09 ................................................................................................................. 34
3.4.2[全部受試者]WMS-III Spatial span 變化 ...................................................... 34
Table 08................................................................................................................... 34
Figure 10 ................................................................................................................. 35
3.4.3[全部受試者]Category fluency of animal 變化.............................................. 36
Table 09................................................................................................................... 36
Figure 11 ................................................................................................................. 37
3.4.4[全部受試者]Category fluency of fruit 變化.................................................. 37
Table 10................................................................................................................... 38
Figure 12 ................................................................................................................. 39
3.4.5[全部受試者]MMSE 變化.............................................................................. 39
Table 11................................................................................................................... 39
Figure 13 ................................................................................................................. 40
3.4.6[全部受試者]CDR 變化 ................................................................................. 41
Table 12................................................................................................................... 41
Figure 14 ................................................................................................................. 42
3.4.7[全部受試者]CDR-SOB 變化........................................................................ 42
Table 13................................................................................................................... 42
3
Figure 15.................................................................................................................. 43
3.4.8[全部受試者]Total NPI score 變化................................................................ 44
Table 14................................................................................................................... 44
Figure 16 ................................................................................................................. 45
3.5[CDR=1 受試者 vs CDR=2 受試者] 餐盒使用前、使用後的認知功能測驗變化
......................................................................................................................................... 45
Table 15................................................................................................................... 46
3.5.1[CDR=1 受試者 vs CDR=2]受試者]CASI 變化........................................... 47
Table 16................................................................................................................... 47
Figure 17 ................................................................................................................. 48
3.5.2[CDR=1 受試者 vs CDR=2]受試者]WAIS-IV Picture completion 變化..... 48
Table 17................................................................................................................... 49
Figure 18 ................................................................................................................. 50
3.5.3[CDR=1 受試者 vs CDR=2]受試者]WMS-III Spatial span 變化................. 50
Table 18................................................................................................................... 51
Figure 19 ................................................................................................................. 52
3.5.4[CDR=1 受試者 vs CDR=2]受試者]Category fluency of animal 變化........ 52
Table 19................................................................................................................... 53
Figure 20 ................................................................................................................. 54
3.5.5[CDR=1 受試者 vs CDR=2]受試者]Category fluency of fruit 變化............ 55
Table 20................................................................................................................... 55
Figure 21 ................................................................................................................. 56
3.5.6[CDR=1 受試者 vs CDR=2]受試者]MMSE 變化........................................ 57
Table 21................................................................................................................... 57
Figure 22 ................................................................................................................. 58
4
3.5.7[CDR=1 受試者 vs CDR=2]受試者]CDR 變化............................................ 58
Table 22................................................................................................................... 59
Figure 23 ................................................................................................................. 60
3.5.8[CDR=1 受試者 vs CDR=2]受試者]CDR-SOB 變化 .................................. 60
Table 23................................................................................................................... 61
Figure 24 ................................................................................................................. 62
3.5.9[CDR=1 受試者 vs CDR=2]受試者]Total NPI score 變化 .......................... 62
Table 24................................................................................................................... 63
Figure 25 ................................................................................................................. 64
3.6[經常使用者 vs 很少使用者] 餐盒使用前、使用後的認知功能測驗變化 ........ 64
Table 25................................................................................................................... 65
3.6.1[經常使用者 vs 很少使用者]CASI 變化..................................................... 66
Table 26................................................................................................................... 66
Figure 26 ................................................................................................................. 67
3.6.2[經常使用者 vs 很少使用者]WAIS-IV Picture completion 變化............... 68
Table 27................................................................................................................... 68
Figure 27 ................................................................................................................. 69
3.6.3[經常使用者 vs 很少使用者]WMS-III Spatial span 變化........................... 70
Table 28................................................................................................................... 70
Figure 28 ................................................................................................................. 71
3.6.4[經常使用者 vs 很少使用者]Category fluency of animal 變化 .................. 72
Table 29................................................................................................................... 72
Figure 29 ................................................................................................................. 73
3.6.5[經常使用者 vs 很少使用者]Category fluency of fruit 變化 ...................... 74
Table 30................................................................................................................... 74
5
Figure 30 ................................................................................................................. 75
3.6.6[經常使用者 vs 很少使用者]MMSE 變化 .................................................. 76
Table 31................................................................................................................... 76
Figure 31 ................................................................................................................. 77
3.6.7[經常使用者 vs 很少使用者]CDR 變化...................................................... 78
Table 32................................................................................................................... 78
Figure 32 ................................................................................................................. 79
3.6.8[經常使用者 vs 很少使用者]CDR-SOB 變化............................................. 80
Table 33................................................................................................................... 80
Figure 33 ................................................................................................................. 81
3.6.9[經常使用者 vs 很少使用者]Total NPI score 變化..................................... 82
Table 34................................................................................................................... 82
Total NPI score changes before and after trial of [frequent users]and [rare users] 經
常使用餐盒族群(受試者編號 1、3、4、5、8、9)及很少使用餐盒族群(受試者
編號 2、6、7、10)，於使用餐盒前後之 NPI 總分沒有顯著差異。................. 83
Figure 34 ................................................................................................................. 83
3.7 編號 10 受試者使用餐盒期間的血液免疫學變化 ................................................. 84
Table 35................................................................................................................... 85
Figure 35 ................................................................................................................. 86
3.8 經常使用者 total CASI score 變化跟 CASI subtests 分數變化的相關性.............. 86
Figure 36 ................................................................................................................. 87
Table 36................................................................................................................... 88
Figure 37 ................................................................................................................. 89
第四章 實驗討論................................................................................................................... 90
4.1 實驗限制................................................................................................................... 90
6
4.2 經常使用者呈現整體認知功能改善趨勢 ............................................................... 90
4.3 視覺感知能力沒有明顯變化................................................................................... 91
4.4 推測智慧餐盒神經免疫調控 neuro-immune modulation 的可能機轉................... 93
第五章 結論........................................................................................................................... 94
第六章 未來展望................................................................................................................... 95
第七章 引用文獻................................................................................................................... 96

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