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  • 學位論文

記憶表現與脂質及基因相關性之研究

The Study of Association of Lipid and Gene with Memory Performance

指導教授 : 賴秋蓮

摘要


背景:阿滋海默氏失智症是後天性大腦病變所引起的全面性心智障礙,其盛行率隨著年齡增高而快速增加,已成為高齡化國家的臺灣之重要醫療課題。膽固醇代謝障礙是失智症致病機轉之ㄧ,而記憶力衰退為失智症的早期症狀,本研究藉正常中老年人,探討血中脂質、調控脂質代謝之相關基因(APOE、CYP46)與記憶表現的關聯性,以期找出失智症的預防因子。 分法:本研究採橫斷面研究設計,無對照組模式,招募209位正常的中老年人(女性佔49.76%;平均年齡為67.87±6.80歲;平均教育11.07±3.91年)。以魏氏記憶測驗量表第三版評估其記憶表現和學習能力,並檢測血清膽固醇、三酸甘油酯、高密度膽固醇、低密度膽固醇的含量,及分析APOE和CYP46的基因多型性。 結果:調整年齡、性別、教育程度和社經地位的影響後,膽固醇偏高者(200-239md/dl)的學習能力比正常值(<200mg/dl)和高膽固醇者(≧240 mg/dL)來的好(p=0.0092);而低密度膽固醇含量與部份情節性長期記憶表現呈正相關。有無APOEε4基因型在記憶表現上並沒有顯著差異;CYP46基因多型性則和記憶表現有顯著相關,尤其是SNP4的AA基因型者在情節性訊息的長期記憶表現顯著較差(p=0.0006)。 結論:CYP46基因多型性和情節記憶衰退有關,特別是SNP4的AA基因型可能是記憶衰退的危險因子,而中老年人的血清膽固醇含量可能會影響其學習表現,但本研究中並沒有觀察到膽固醇含量、APOE和CYP46基因多型性會交互影響記憶的表現。

並列摘要


Alzheimer’s disease is a neurodegenerative disease, manifested by global cognitive deterioration. The prevalence of Alzheimer’s disease is increased by aging and becomes a major health problem, especially in ageing society, such as Taiwan. Previous studies have shown that high serum total cholesterol is a risk factor for dementia, the clinical hallmarks are including progressive memory loss. The objective of this study was to examine the relation of plasma lipid levels and lipid-related gene(APOE, CYP46) with memory performance in milddle-aged and older adults without dementia. Our study used cross-section design and without control subjects. A total of 209 cognitively intact participants were recruited, the mean age(SD) was 67.87(6.80) years, the mean education was 11.07(3.91) years, 49.76% were women. Memory and learning function were measured by logical memory (I)(II), world list (I)(II) and spatial span of the Wechsler Memory Scale-III (WMS-III). Serum total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol, APOE and CYP46 gene polymorphisms were analyzed. After adjustment for age, gender,education and socioeconomic status, participants with moderate total cholesterol levels (200-239mg/dL) performed better well than participants with desirable (<200 mg/dL) and high total cholesterol levels (≧240 mg/dL) in learning ability(p=0.0092). We also found positive linear association of LDL with long-term memory on logical memory test. There was no significant difference between with and without APOEε4 genotype on Memory performance. We observed the significant associations between CYP46 gene polymorphisms and logical memory performance, SNP4 especially:subjects with AA genotype performed less well (p=0.0006). In conclusion, CYP46 gene polymorphisms may play an important role in episodic memory performance, furthermore SNP4-AA genotype may be a risk factor of memory impairment. And moderate total cholesterol are associated with better learning performance. Finally, Cholesterol, APOE and CYP46 gene polymorphisms have no interaction on memory performance.

參考文獻


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