Omega-3, isoflavones & amyloid deposition in cognitively normal elderly Japanese

 描述(申请人提供)：神经成像的最新进展使使用匹兹堡化合物B(PIB)评估大脑中的淀粉样蛋白沉积成为可能。淀粉样蛋白沉积是阿尔茨海默病(AD)的独立危险因素。认知正常(NC)的80-89岁老年人大多有淀粉样蛋白沉积。没有研究发现在患有NC的老年人群中淀粉样蛋白沉积的患病率很低。找到这样的人群是确定AD风险因素的第一步。日本人的寿命最长；虽然他们的载脂蛋白E4(AD的主要遗传风险因素)的患病率与美国相似，但日本人的饮食结构有很大的不同，在过去50年里，他们的饮食摄入量显著增加，包括海洋omega-3脂肪酸(omega-3 FA)和大豆异黄酮(ISF)(两者的摄入量都是美国的10倍)。许多观察性研究报告称，膳食中摄入omega-3脂肪酸与痴呆症和阿尔茨海默病的发病率呈负相关。日本最近的一项研究报告称，大豆的高饮食摄入量与痴呆症和AD的发病率呈负相关。大豆是ISF的来源。来自少数患有NC的老年志愿者的建议证据表明，日本人淀粉样蛋白沉积的患病率非常低。我们假设：1)日本80-89岁NC老年人脑内淀粉样蛋白沉积的发生率显著低于美国；2)在80-89岁NC日本老年人中，omega-3 FA和ISF的中年血清水平与晚年淀粉样蛋白沉积显著负相关。为了验证我们的假设，我们将招募200名年龄在80-89岁的日本男性和女性(每人100名)，其中NC是从日本的Suita研究中随机选择的：1994年对6,406名年龄在30-79岁之间的人进行的基于人群的前瞻性队列研究。我们将根据美国研究的标准，为PIB检查这200个对象。我们还将使用储存的血清样本来检验每种omega-3脂肪酸和ISF的中年水平与晚年淀粉样蛋白沉积的相关性。脑内淀粉样蛋白沉积的低患病率以及omega-3脂肪酸和/或ISF与淀粉样蛋白沉积的显著负相关的发现将对AD的病因研究和潜在的预防产生重大影响。

 DESCRIPTION (provided by applicant): Recent progress in neuroimaging has made it possible to evaluate amyloid deposition in the brain with Pittsburgh compound B (PiB). Amyloid deposition is an independent risk factor for Alzheimer's disease (AD). The majority of elderly aged 80-89 with normal cognition (NC) have amyloid deposition. No studies have found a population where prevalence of amyloid deposition is low among elderly with NC. Finding such a population is a first step to identifying risk factors for AD. Japanese have the greatest longevity; while their prevalence of apolipoprotein E4, the major genetic risk factor for AD, is similar to the US, Japanese have a considerably different diet characterized by markedly high dietary intake of marine omega-3 fatty acids (omega-3 FAs) and soy isoflavones (ISF) (both are >10x higher than in the US) for the past 50 years. Many observational studies reported that dietary intake of omega-3 FAs is inversely associated with incident dementia and AD. A recent study in Japan reported that high dietary intake of soy, which is the source of ISF, is inversely associated with incident dementia and AD. Suggested evidence from a small number of elderly volunteers with NC shows that Japanese have very low prevalence of amyloid deposition. We hypothesize that 1) Japanese elderly aged 80- 89 with NC have significantly lower prevalence of amyloid deposition in the brain than in the US and 2) in Japanese elderly aged 80-89 with NC, midlife serum levels of each of omega-3 FAs and ISF have significant inverse associations with late-life amyloid deposition. To test our hypotheses, we will enroll 200 Japanese men and women (100 each) aged 80-89 with NC randomly selected from the Suita Study in Japan: a population- based prospective cohort study of 6,406 subjects aged 30-79 at baseline in 1994. We will examine these 200 subjects for PiB standardized to US studies. We will also examine the association of midlife levels of each of omega-3 FAs and ISF with late-life amyloid deposition using stored serum samples. The findings of low prevalence of amyloid deposition in the brain and significant inverse associations of omega-3 FAs and/or ISF with amyloid deposition will have major impact on research into the etiology and potentially the prevention of AD.