The Study of Cognitive Function in Elderly 卓良珍、吳淑姿
E-mail: 363557@mail.dyu.edu.tw
ABSTRACT
The study of cognitive decline and mental status in elderly person showed that age, head trauma and stroke were the risk factors for dementia and mild cognitive impairment (MCI). We found that normal subjects had often habits of physical exercise while dementia person lacked physical exercise. In our survey of declined cognition in elderly we found that almost all dementia patient had stroke.
Ninety-seven valid MCI cases were followed up, and about 29.9% becoming to dementia (probable Alzheimer’s disease) in third year. This was similar to Dr. Peterson’s predication that 12.37% of MCI deteriorated to dementia (AD) every year. 14.43% of patient with MCI developed to depression, and 9.23% recover to normal status, and around 46.3% remained in MCI status. ApoE4 allele is a known risk factor of cognitive regression to MCI and dementia. We found that ApoE4 allele in the depression and normal groups was smaller than in the dementia group with a odds ratio (OR)=5.74 and in the MCI group OR=5.5. The serum level of high-density lipoprotein cholesterol (HDL-C) was lower in the dementia group than in the MCI and normal groups. This suggests that the presence of ApoE4 allele combine with a low serum level of HDL-C could be the risk factors for Alzheimer’s disease.
Therefore, the prevention and treatment of dementia or others cognitive decline could be done by very earlier AD-8 dementia screening. In study of UBQLN1 (Ubiquilin 1) gene polymorphism (UBQ-8i), all 187 subjects were AA-type gene without G allele.
Therefore, we concluded that this gene mutation in Taiwan was rare and the single nucleotide polymorphism (SNP) of UBQ-8i was not compatible with Hardy-Weinberg law. Since all UBQLN1 gene of rs12344615 site were AA-type allele, we suspected that there was a ethnic genetic difference between Taiwanese and Caucasians in UBQLN1 gene of UBQ-8i site. In intervention study of MCI with Art therapy, the mean age of the experimental and control groups were 82.83±3.703 and 82.89±3.367 respectively, P=0.956.
After 16 weeks of intervention with visual expression art therapy, participants from the experimental group improved their cognitive function significantly, P=0.009, especially with the language function P=0.001.
Keywords : Cognitive decline、Mild cognitive impairment / MCI、ApoE4、Alzheimer's Disease / AD、Art therapy、Dementia
、Ubiquilin 1
Table of Contents
封面內頁 簽名頁 中文摘要iii 英文摘要v 誌謝vii 目錄ix 圖目錄xii 表目錄 xiv 1. 緒論1 2. 文獻回顧3 2.1 社會結構的改變3 2.2 老年人的綜合症候群6 2.3 老年認知功能15 2.3.1 認知功能的定義15 2.3.2 失智症的定義20 2.4 阿茲海默氏病23 2.4.1 憂鬱症 常常是認知功能退化的早期症狀38 2.5 UBQLN 1基因檢測41 2.5.1 UBQLN 1基因是兩型AD的危險因子41 2.5.2 UBQLN 1與 泛蛋白ubiquitin42 2.5.3 ubiqilin與γ分泌?43 2.6 AD-8極早期失智症篩檢44 2.6.1 老化與失智症44 2.6.2 AD早期診斷的重要 性45 2.6.3 失智症評估工具的侷限46 2.6.4 個體內比較與個體間比較47 2.6.5 AD-8中文版量表48 2.7 藝術治療50 2.7.1 藝術治 療的定義52 2.7.2 藝術治療發展史53 2.7.3 藝術治療的目的55 2.7.4 藝術治療的功效55 2.7.5 藝術治療使用在老年族群的功 效56 2.7.6 藝術治療的評估機制57 3. 材料與方法58 3.1 老年人精神狀態與認知功能減退58 3.1.1 選取樣本的條件58 3.1.2 研 究工具及進行步驟58 3.2 衰弱住院老人的精神狀態及其相關危險因子62 3.2.1 選取樣本的條件62 3.2.2 研究工具及進行步 驟62 3.3 AD-8極早期失智症篩檢69 3.3.1 選取樣本的條件69 3.3.2 研究工具及進行步驟70 3.3.2.1 收集基本資料70 3.3.2.2 樣 本評估第一階段篩檢70 3.3.2.3 第二階段評估71 3.3.2.4 第三階段評估71 3.3.3 「輕度知能減退」MCI診斷標準71 3.3.4 失智 症診斷流程72 3.4 UBQLN1基因的多態性(UBQ-8i)74 3.4.1 收集樣本DNA74 3.4.2 UBQLN 1基因檢測74 3.4.3 統計方法75 3.5 輕度認知減退的介入性研究-藝術治療75 4. 結果與討論80 4.1 老年人精神狀態與認知功能減退之研究80 4.1.1 老年精神狀 態80 4.1.2 老年認知功能減退之調查92 4.2 衰弱住院老人的精神狀態及其相關危險因113 4.3 AD-8極早期失智症篩檢方法之 探討121 4.4 UBQLN1基因的多態性(UBQ-8i) 之研究132 4.5 輕度認知減退的介入性研究-藝術治療136 5. 結論163 參考文 獻166 附錄173 圖目錄 圖2.1 60歲以上世界人口比例4 圖2.2 世界各國老年人口從7％升至14％所需的年數表8 圖2.3 神經血管 反應的生理改變9 圖2.4 腦血管血流傳輸系統10 圖2.5 與年齡相關之慢性疾病12 圖2.6 失能與死亡率有相關的疾病14 圖2.7 輕度認知功能減退MCI分類圖19 圖2.8 ApoE2，E3 脂蛋白可以棄除Aβ42(A)。ApoE4脂蛋白無法棄除Aβ42(B)25 圖2.9 類澱 粉蛋白連鎖反應之三，類澱粉斑形成導致發炎反應 26 圖2.10 神經細胞樹狀突蛋白合成的流程28 圖2.11 阿茲海默氏病發作 的症狀型態30 圖2.12 類澱粉蛋白斑導致纏結形成33 圖2.13 廣泛神經／觸突、功能異常、神經傳導缺陷，神經凋零神經纖 維纏結類澱粉蛋白斑破壞神經細胞內、外功能，神經凋零細胞逐漸死亡34 圖2.14 類澱粉前軀蛋白演變成類澱粉蛋白流程35 圖2.15 主要乙醯鹼酸激素精油腦幹投射37 圖2.16 神經生長因子促神經細胞復生40 圖2.17 成人海馬迴神經細胞生成圖51
圖4.1 脂蛋白E對偶基因出現頻率之比較99 表目錄 表2.1 台灣人口結構百分比5 表2.2 失能與死亡率有相關的疾病之百分 比13 表4.1 精神狀態分類四組間年齡的Kruskal Wallis 檢定結果81 表4.2 精神狀態分類四組之間生活習性的卡方檢定結果83 表4.3 精神狀態分類四組之間身體疾病的卡方檢定87 表4.4 精神狀態分類四組間量表的Kruskal Wallis檢定結果89 表4.5 精神 狀態分類四組間生理生化檢驗的Kruskal Wallis 檢定結果91 表4.6 脂蛋白E 之基因型97 表4.7 脂蛋白E 對偶基因之出現頻 率98 表4.8 Cystatin C 之基因型100 表4.9 Cystatin C多型性對偶基因頻率101 表4.10 總膽固醇之量測結果102 表4.11 三酸甘 油脂之量測結果103 表4.12 腎功能 (BUN) 之量測結果104 表4.13 腎功能 (Creatinine) 之量測結果105 表4.14 高密度脂蛋白 (HDL-C) 之量測結果106 表4.15 總膽固醇/高密度脂蛋白 (Chol-HD_C) 之量測結果107 表4.16 糖化血色素 (HbA1c) 之量測結 果108 表4.17 高血壓病史109 表4.18 心臟病病史110 表4.19 糖尿病史111 表4.20 高膽固醇病史112 表4.21 三組之平均年齡116 表4.22 憂鬱症 20人 (輕、中度憂鬱症14人、重度憂鬱症6人)117 表4.23 正常組與MCI組平均數之比較118 表4.24 正常組與失 智症組平均數之比較119 表4.25 MCI組與失智症組ADL、IADL及Braden平均數之比較120 表4.26 各據點之平均年齡122 表4.27 台中榮民總醫院老年心理衛生門診AD-8分數大於或等於2分者124 表4.28 台中榮民總醫院老年心理衛生門診AD-8分 數小於或等級1者126 表4.29 兩組前測之MMSE平均分數比較128 表4.30 兩組後測之MMSE平均分數比較130 表4.31 兩組之 年齡平均數比較137 表4.32 兩組實驗前之MMSE平均分數比較139 表4.33 兩組實驗後之MMSE平均分數之比較141 表4.34 實驗組於藝術治療前、後MMSE平均分數之比較143 表4.35 對照組於實驗前、後其MMSE平均分數之比較145 表4.36 兩組 於實驗前、後其GDS平均分數之比較147 表4.37 對照組於實驗前、後其GDS平均分數之比較149 表4.38 實驗組於實驗前、
後GDS平均分數之比較151 表4.39 兩組於實驗前IADL平均分數之比較153 表4.40 兩組於實驗後IADL平均分數比較155 表4.41 對照組實驗前、後IADL平均分數157 表4.42 實驗組實驗前、後IADL平均分數159
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