前言：近年來在阿茲海默症(AD)的治療，仍處瓶頸膠著狀態。找出有效的治療方法是重要的課題。AD在ß澱粉樣蛋白病理沉積啟動下後續的神經細胞萎縮和死亡。神經細胞間的神經突觸可塑性調節受到影響，ß澱粉樣蛋白病理沉積導致長期增強作用和長期抑制作用間的平衡受到破壞。長期增強作用和長期抑制作用被認為是學習及記憶是兩重要的機轉。文獻回顧在比較各種非侵襲性性腦刺激術顯示，經顱直流電刺激(tDCS)以陽極電流刺激去極化，促使大腦皮質興奮性，在神經細胞啟動鈣離子流入，誘發長期增強作用; 經陰極使過極化，抑制興奮性而誘發長期抑制作用。並且tDCS可調節神經傳導物質、改變大腦震盪活動、促使腦血流和功能性連結增加，進而改善認知能力。學理上tDCS透過上述各種作用減緩ß澱粉樣蛋白堆積帶來的認知障礙，可能對AD認知有正面效益。透過文獻回顧顯示tDCS 的參數，包括電極片大小、陽陰極定位、電流強度2mA、刺激持續時間、連續次數的tDCS施作方式，影響在AD 的認知功能的效益。
目的：本研究的主要目的是評估 tDCS 在 AD 中的作用，透過認知測驗和量化腦波測試 tDCS對阿茲海默症的效益。次要目的是確立 tDCS 的參數。
研究方法：本研究納入30位CDR在0.5-1極輕度至輕度以內之AD受試者。實驗採雙盲交叉試驗，探討兩週內以電流2mA，陽極設在左側背外側前額葉區，陰極在右側眶上區，每天每次三十分鐘，連續十次tDCS對AD認知障礙症的療效。受試者隨機分配接受(1)經顱直流電刺激組(實驗組)及(2)偽刺激組(對照組)。每組在在試驗前後先接受各種認知測驗(包括臨床失智評估量表(CDR)、簡易智能量表(MMSE)、認知功能障礙篩檢量表(CASI)、神經精神評估量表(NPI)、威斯康辛卡片分類測驗(WCST))以及腦波。在腦波以量化分析探討tDCS前後的各種波頻的功率比(power ratio)變化。透過各種認知測驗及腦波各種波頻的功率比變化探討tDCS的效益。
結果：分析在AD組接受兩週十次tDCS後，CASI和MMSE有明顯改善。在顯示tDCS 對AD的認知有正面的效益，特別是專注力和計算concentration and calculation)、定向能力(orientation)、語言能力(language ability)、分類語言流暢性(categorical verbal fluency)、構圖(drawing)有保護的效果。在WCST分項的正面效應，顯示tDCS對概念形成(concept formation)、認知彈性和正確率(cognitive flexibility and accuracy)和抽象思考能力(abstractive thinking ability)上的正面效益。但對記憶力未有明顯協助。NPI 評估顯示 tDCS 後焦慮項目有顯著改善。分析量化腦波的結果支持tDCS結果有減緩AD組雙額葉前側慢波且增加快波等正面的效益，與tDCS主要電刺激區域分佈一致。
結論：目前研究結果顯示tDCS電刺激對AD的認知功能正面的效益，腦波結果支持tDCS 的正面影響及區域分佈。

Background: The most common degenerative dementia is Alzheimer's disease (AD). Current therapies for AD are limited in terms of their efficacy to improve their cognitive dysfunction. In AD, the soluble oligomers of amyloid-beta could induce a significant reduction of long-term potentiation (LTP) and facilitate the induction of long term depression (LTD). The transcranial direct current stimulation (tDCS) has been proposed to promote both LTP and LTD which are significantly considered as the important mechanisms associated with the learning and memory. It was assumed to modulate the synaptic environment and calcium reflux, which could influence the protein synthesis and brain-derived neurotrophic factor releasing, modulate the LTP and LTD, and subsequently influence the regional cerebral blood flow and functional connectivity. However, the efficacy of tDCS on AD is under debate due to the variation in the evaluation criteria, number and length of stimulation sessions, indensity and type of stimulation, or target areas.
Objective: The primary objective of this study was to evaluate the tDCS effects on cognitive function, behavioral and psychological symptoms in AD, by the neuropsychological tests and quantitive electroencephalogram (EEG). The secondary objective was to establish the useful parameters of tDCS in AD.
Method: There were 30 AD included in this randomized and double blind study. The Clinical Dementia Rating (CDR) of all participants ranged from 0.5 to 1. In each active session, we applied tDCS with a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in the active group. tDCS with the anodal electrode was on the left dorsal lateral prefrontal cortex (LDLPFC) and the cathodal electrode was on the right supraorbital area. All subjects received a series of neuropsychological tests, which included CDR, Mini-Mental State Examination (MMSE), Cognitive Abilities Screening Instrument (CASI), Wisconsin Card Sorting Test (WCST), Neuropsychiatry Inventory (NPI) and EEG before and after 10 sessions intervention. Signal acquisition and processing were performed on pre- and post-intervention resting state EEG. Quantitative EEG data were analyzed with Persyst 13 EEG review and analysis software for the power spectrum analysis of 5 frequency, delta, theta, alpha, beta and gamma bands. Wilcoxon signed ranks test and Mann-Whitney U test were used to assess the differences among groups.
Result: The results showed a significant improvement of CASI scores after the tDCS, especially for the “concentration and calculation”, “orientation”, “language ability”, “visual construction” and “categorical verbal fluency” items. MMSE and WCST scores in all domains of “concept formation”, “abstract thinking”, “cognitive flexibility”, and “accuracy”. For the sham group, scores on all neuropsychological tests did not differ between baseline and after the intervention. The NPI assessment showed the significant improvements in anxiety items after the tDCS. Most of these results were not found for the sham group. The EEG results suggested that the tDCS could reduce the slower waves and increase the faster waves on the bilateral anterior frontal areas. The results of significant change in faster or slower band power ratio change were found to be consistent with the main electrical stimulation areas by tDCS.
Conclusion: These results of neuropsychological tests and quantitative EEG suggested that tDCS on LDLPFC could impove the cognitive dysfuncion in AD.

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