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

项目总结 这项提议的科学前提是，食用深加工食品有助于认知 随着年龄的增长而下降。这些饮食影响可能会导致健康差异，认知能力下降是由于已知的 在低收入人群中更多地消费高加工食品。虽然有许多因素与之相关 以深加工食品为特征的饮食的影响，包括取代健康食品和 与这些相关的无数营养素，我们认为，特别是两种营养素可能会有影响 通过已知或正在出现的影响大脑功能的途径。首先，有证据表明，经过高度加工的 食物通过以磷为基础的食品添加剂增加食物磷的摄入量。 ≥含量70%。血管危险因素预示认知功能下降，过量的磷可能会增加心血管疾病的风险。然而， P在认知功能下降中的作用尚不清楚。一个新的途径是成纤维细胞的代偿性升高 生长因子23(FGF23)，血管钙化和心血管疾病的预测因子。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，高磷饮食减少了Klotho的分泌。 过量的磷摄入可能通过调节FGF23来降低klotho和损害认知功能，但 人类数据仍然稀少。P还会升高甲状旁腺激素(PTH)，PTH可以预测心血管疾病的死亡率和 有脑梗塞的迹象。其次，维生素B6(B6)是≥100代谢反应的关键辅助因素，很容易 与其他维生素B不同的是，维生素B在食品加工过程中流失，不会被添加回浓缩的谷物中。我们已经展示了 低B6水平与炎症、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人男性的研究表明， 饮食和血浆B6(吡哆醇-5‘-磷酸，PLP)均降低，认知功能减退3年。拉丁裔似乎是 与非西班牙裔白人相比，认知障碍的负担不成比例。此外，最近 有证据表明，波多黎各人患全球认知功能低下的几率是 墨西哥人。随着美国拉美裔人口的增长和老龄化可能会导致美国人口的大幅增长 认知下降的负担，关键是我们必须提高对预防性风险因素的理解，这些因素可能 告知干预措施。我们将使用波士顿波多黎各健康研究(BPRHS)的数据，这是一个纵向的 美国本土波多黎各人(45-74岁)与饮食、营养生物标记物和认知功能的队列研究 在基线和2年和5年随访时可获得测试数据。我们将招募BPRHS参与者回国(~8年 从基线开始)，进行一系列重复的认知检查，对于子集，进行核磁共振扫描。我们将量化 加工食品摄入量、P状态(血清P、FGF23、Klotho和PTH)、膳食B6、 和PLP，作为暴露，认知下降~8年(心理测量测试)和脑结构，大脑 结果是8岁时的脑梗塞、白质完整性和连通性(MRI)。进一步说，潜在的中介语 炎症(C反应蛋白、IL-6和肿瘤坏死因子-α)和胰岛素抵抗(HOMA-IR)的作用将被测量。

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.