Dietary Quality, Cognitive Decline and Brain Health in Puerto Rican Adults

项目摘要 这一建议的科学前提是，消费高度加工的食品有助于认知 随着年龄的增长而下降。这些饮食影响可能导致认知能力下降的健康差异， 低收入人群中高度加工食品的消费量增加。虽然许多因素与 以高度加工食品为特征的饮食的影响，包括健康食品的替代， 与此相关的营养素种类繁多，我们认为有两种营养素可能特别有影响， 通过已知的或新出现的影响大脑功能的途径。首先，有证据表明， 食物通过含磷食品添加剂增加食物中磷的摄入量， 含量≥ 70%。血管危险因素可预测认知能力下降，过量的磷可增加CVD风险。然而，在这方面， P在认知能力下降中的作用尚不清楚。一种新的途径是成纤维细胞的代偿性升高 生长因子23（FGF 23），血管钙化和CVD的预测因子。Klotho，一种公认的抗衰老因子， 可能对心血管疾病和认知能力下降有保护作用。在小鼠中，高磷饮食减少klotho分泌。 过量的磷摄入可能会降低klotho，并通过调节FGF 23损害认知功能，但 人类数据仍然很少。P还升高甲状旁腺激素（PTH），其预测CVD死亡率， 存在脑梗塞。其次，维生素B6（B6）是≥100种代谢反应的关键辅因子， 与其他B族维生素不同的是，在食品加工过程中丢失的维生素不会被添加到富含维生素的谷物中。我们已经表明 低B6状态与炎症、氧化应激、代谢综合征、糖尿病和 波多黎各成年人的抑郁症状早期对非西班牙裔白色男性的研究显示， 饮食和血浆B6（吡哆素-5 '-磷酸盐，PLP）的水平与3年认知能力下降有关。拉丁裔似乎是 与非西班牙裔白人相比，他们不成比例地承受着认知障碍的负担。此外，最近 有证据表明，波多黎各人的全球认知功能低下的几率是美国人的两倍。 墨西哥人随着美国拉丁裔人口的增长和老龄化， 认知能力下降的负担，关键是我们要提高我们对预防风险因素的理解， 知情干预。我们将使用波士顿波多黎各健康研究（BPRHS）的数据， 美国本土波多黎各人（45-74岁）饮食、营养生物标志物和认知功能的队列研究 在基线和2年和5年随访时获得测试数据。我们将招募BPRHS参与者返回（约8年 从基线）进行认知检查的重复组合，并且对于子集，进行MRI扫描。我们将量化 加工食品消费，P状态（血清P，FGF 23，klotho和PTH），膳食B6， 和PLP，作为暴露，具有~8年认知能力下降（心理测量测试）和脑结构，大脑 梗死、白色物质完整性和连接性（MRI）作为约8年的结局。进一步的潜在中介 将测量炎症（CRP、IL-6和TNF-α）和胰岛素抵抗（HOMA-IR）的作用。

PROJECT SUMMARY The scientific premise of this proposal is that consumption of highly processed foods contributes to cognitive decline with aging. These dietary effects may lead to health disparities in cognitive decline due to the known greater consumption of highly processed foods in low-income populations. While many factors are associated with the effects of a diet characterized by highly processed foods, including displacement of healthy foods and the myriad of nutrients associated with these, we propose that two nutrients, in particular, may have effects through known or emerging pathways that affect brain function. First, there is evidence that highly processed foods contribute to greater intake of phosphorus (P) through P-based food additives which can increase food P content by ≥70%. Vascular risk factors predict cognitive decline and excess P may elevate CVD risk. However, the role of P in cognitive decline remains unclear. One novel pathway is compensatory elevation in fibroblast growth factor 23 (FGF23), a predictor of vascular calcification and CVD. Klotho, a putative anti-aging factor, may be protective against CVD and cognitive decline. Among mice, a high P diet reduced klotho secretion. Excessive P consumption may lower klotho and impair cognitive function through modulation of FGF23, but human data remain sparse. P also elevates parathyroid hormone (PTH), which predicts CVD mortality and presence of cerebral infarcts. Second, vitamin B6 (B6), a critical cofactor for ≥100 metabolic reactions, is easily lost with food processing and unlike other B vitamins is not added back to enriched grains. We have shown that low B6 status was associated with inflammation, oxidative stress, metabolic syndrome, diabetes and depressive symptoms in Puerto Rican adults. Earlier work with non-Hispanic white men, showed associations of both diet and plasma B6 (pyridoxl-5'-phosphate,PLP) with 3 y cognitive decline. Latinos appear to be disproportionately burdened by cognitive impairment compared to non-Hispanic whites. Moreover, recent evidence suggests that Puerto Ricans have >twice the odds of low global cognitive function compared to Mexicans. With the growing and aging Latino population in the U.S likely to contribute to major increases in the burden of cognitive decline, it is critical that we improve our understanding of preventive risk factors that may inform interventions. We will use data from the Boston Puerto Rican Health study (BPRHS), a longitudinal cohort study of U.S. mainland Puerto Ricans (45-74 y) with diet, nutritional biomarkers, and cognitive function testing data available at baseline and 2 and 5 y follow-up. We will recruit BPRHS participants to return (~ 8-y from baseline) for a repeat battery of cognitive exams and, for a subset, an MRI scan. We will quantify the associations between processed foods consumption, P status (serum P, FGF23, klotho, and PTH), dietary B6, and PLP, as exposures, with ~8 y cognitive decline (psychometric testing) and brain structure, cerebral infarcts, white matter integrity, and connectivity (MRI) at ~8 y, as outcomes. Further the potential mediative roles of inflammation (CRP, IL-6, and TNF-α) and insulin resistance (HOMA-IR) will be measured.