Rajendra Anjana, Bondonno Nicola P, Murray Kevin, Zhong Liezhou, Rainey-Smith Stephanie R, Gardener Samantha L, Blekkenhorst Lauren C, Doré Vincent, Villemagne Victor L, Laws Simon M, Brown Belinda M, Taddei Kevin, Masters Colin L, Rowe Christopher C, Martins Ralph N, Hodgson Jonathan M, Bondonno Catherine P
Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia.
Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; The Danish Cancer Institute, Copenhagen, Denmark.
J Prev Alzheimers Dis. 2025 Jun;12(6):100161. doi: 10.1016/j.tjpad.2025.100161. Epub 2025 Apr 11.
Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia.
Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD).
Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had β-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline.
Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates of cerebral β-amyloid (Aβ) deposition, measured using PET, and rates of brain atrophy, measured using MRI, were assessed between baseline and 126-months follow-up, at intervals of 18 months. Multivariable-adjusted linear mixed effect models were used to examine associations between baseline source-specific nitrate intake and rates of (i) cerebral Aβ deposition and (ii) brain atrophy, over the 126 months of follow-up. Analyses were carried out following stratification of the sample by established dementia Alzheimer's disease (AD) risk factors including sex and presence or absence of the apolipoprotein E (APOE) ε4 allele.
In women carriers of the APOE ε4 allele, higher plant sourced nitrate intake (median intake 121 mg/day), was associated with a slower rate of cerebral Aβ deposition [β: 4.47 versus 8.99 Centiloid (CL) /18 months, p < 0.05] and right hippocampal atrophy [-0.01 versus -0.03 mm3 /18 months, p < 0.01], after multivariable adjustments. Moderate intake showed protective associations in men carriers and in both men and women non-carriers of APOE ε4.
Associations were observed between plant-derived nitrate intake and cerebral Aβ deposition, particularly in high-risk populations (women and APOE ε4 carriers). Associations were also observed for brain volume atrophy, however these exhibited subgroup variability without clear patterns relative to sex and APOE ε4 allele carriage. These findings suggest a potential link between plant-sourced nitrate and AD related neuroimaging markers of brain health improved brain health, but further validation in larger studies is required.
膳食硝酸盐作为一氧化氮（NO）的前体，可能有助于大脑健康并预防痴呆症。
我们的主要目的是研究膳食硝酸盐是否与与阿尔茨海默病（AD）相关的大脑健康神经影像学标志物有关。
研究参与者是来自澳大利亚衰老成像、生物标志物和生活方式研究（AIBL）的认知未受损个体，他们进行了β淀粉样蛋白正电子发射断层扫描（PET）（n = 554）和磁共振成像（MRI）扫描（n = 335），并在基线时完成了食物频率问卷调查。
使用综合硝酸盐食物成分数据库估计特定来源的硝酸盐摄入量。在基线和126个月随访期间，每隔18个月评估一次使用PET测量的脑β淀粉样蛋白（Aβ）沉积率和使用MRI测量的脑萎缩率。使用多变量调整线性混合效应模型来检查基线时特定来源的硝酸盐摄入量与（i）脑Aβ沉积率和（ii）脑萎缩率在126个月随访期间的关联。在根据包括性别和载脂蛋白E（APOE）ε4等位基因的存在与否等既定的痴呆症阿尔茨海默病（AD）风险因素对样本进行分层后进行分析。
在APOE ε4等位基因的女性携带者中，较高的植物源硝酸盐摄入量（中位数摄入量为121毫克/天）与脑Aβ沉积率较慢相关[β：4.47对8.99 Centiloid（CL）/18个月，p < 0.05]和右侧海马萎缩[-0.01对-0.03立方毫米/18个月，p < 0.01]，经过多变量调整。中等摄入量在APOE ε4的男性携带者以及男性和女性非携带者中显示出保护关联。
观察到植物源性硝酸盐摄入量与脑Aβ沉积之间存在关联，特别是在高危人群（女性和APOE ε4携带者）中。还观察到与脑容量萎缩有关联，然而这些关联在亚组中存在变异性，相对于性别和APOE ε4等位基因携带情况没有明确模式。这些发现表明植物源硝酸盐与AD相关的大脑健康神经影像学标志物之间存在潜在联系，可能改善大脑健康，但需要在更大规模的研究中进一步验证。
