2017-08-012024-05-18https://scholars.lib.ntu.edu.tw/handle/123456789/700945摘要：失智症常見於老年，主要病因是神經系統退化與腦血管病變、且在臨床發病前已進展多年，因為目前並沒有根治方法，因此調控相關危險因子的預防治療便相對重要。目前許多世代研究的整合分析顯示，某些飲食類型與特殊營養素可以顯著降低失智風險；而這些營養素的神經保護功能是多面向卻也有趨集性。許多退化性失智症的致病機轉都認為與附基因調控有關，如最常見的阿茲海默症其疾病相關基因如APP、PSEN1、APOE 和BACE1 都顯示有甲基化改變。具有神經保護功能的營養素、如甲基分子團供應者(膽鹼、甜菜鹼、甲硫胺酸與葉酸)，可藉由改變DNA 與組織蛋白的甲基化形式，來影響基因表現、進而達到增強記憶與其他心智功能效果。睡眠疾病常見於失智患者，甚至是在前臨床時期；神經退化疾病會破壞腦部的晝夜生理節奏，產生失眠、異樣睡眠障礙、多眠、睡眠中止與夜間異動症等。然而這些睡眠障礙在不同的退化性失智症其生成原因也有所不同。愈來愈多的證據顯示附基因調控可以調整睡眠與日夜週期，在失智患者某些生理節奏基因的附基因甲基化也較為明顯。皮質醇的濃度失調也被報告與睡眠品質下降及失眠有關，特殊營養方式(如地中海式飲食)可以矯正代謝性酸中毒、重建皮質醇正常調節、改善睡眠品質、最終減少知能的損害。由此可知飲食(營養)與睡眠在失智病程的調控佔有重要腳色、且彼此互相影響；然而近來台灣並無各類失智患者的飲食營養狀態與睡眠疾病的本土研究。因此，我們設計這個三年期的前瞻性世代研究，除了流行病學上的調查研究，並深入探討營養與睡眠對於失智疾病進展的影響，特別針對附基因調控機制。<br> Abstract: Dementia is a syndrome of cognitive and functional decline, commonly occurring in later life as a resultof neurodegenerative and cerebrovascular processes beginning earlier in the life course. In the absence ofcurative treatments, modifiable risk factors for prevention play important role. Recent meta-analysis ofavailable cohort studies indicated that several dietary patterns and nutritional components are associatedwith a significantly reduced risk of dementia. The nutritional components may exert their protectivefunction in multiple and convergent ways. Epigenetic mechanisms has been also investigation with thepathogenesis of many neurodegenerative disorders with dementia. For example, APP, PSEN1, APOE, andBACE1 which are primarily involved in AD pathogenesis have displayed changes in methylation patterns.Several neuroprotective nutrients, such as methyl group donor (choline, betaine, methionine and folate) canalter methylation patterns of DNA and histones which in turn results in changes in gene expression, and thenenhance cognition, memory and other impaired functions.Sleep disorders are common in dementia, and even in the preclinical stage. Neurodegenerative diseasesinvolve disruption of circadian system that manifests as insomnia, parasomnia, hypersomnia, sleep apnea, orexcessive nocturnal motor activity. However, the etiologies of different sleep disturbances within thesedifferent neurodegenerative conditions also are varied. More and more evidence indicates that epigeneticmechanisms regulate sleep and sleep-wake cycles. Epigenetic methylation of some circadian genes wasmore prevalent in dementia patients has been reported. Deregulated cortisol concentrations were showncorrelated with diminished sleep quality and insomnia. Specific diets (e.g. Mediterranean type) mightreverse metabolic acidosis, restoring cortisol regulation, sleep quality and consequentially preservecognitive functions or reduce cognitive impairmentsDiet and sleep both may play important role and interactively in the regulation of dementia diseaseprocess. However, there is no precise data of diet status and sleep disorder prevalence in different dementiain Taiwan groups recently. Therefore we launch this 3 years-cohort study for the epidemiologicalinvestigation, we also try to figure out their influence on disease progression with focus on epigeneticmechanism.失智症飲食睡眠疾病甲基供應微量營養素附基因調控DementiaDietSleep disorderMethyl-donor micronutrientEpigenetic