Habitual dietary nitrate intake and cognition in the Australian Imaging, Biomarkers and Lifestyle Study of ageing: A prospective cohort study

Background & aims: Dietary nitrate improves cardiovascular health via a nitric oxide (NO) pathway. NO is key to both cardiovascular and brain health. There is also a strong association between vascular risk factors and brain health. Dietary nitrate intake could therefore be associated with better cognitive function and reduced risk of cognitive decline. This is yet to be investigated. The aim of this study was to investigate the association between habitual intake of dietary nitrate from sources where nitrate is naturally present, and cognitive function, and cognitive decline, in the presence or absence of the apolipoprotein E (APOE) & epsilon;4 allele.Methods: The study included 1254 older adult participants of the Australian Imaging, Biomarkers and Lifestyle Study of Ageing who were cognitively normal at baseline. Plant-derived, vegetable-derived, animal derived nitrate (not including meat where nitrate is an allowed additive), and total nitrate intakes were calculated from baseline food frequency questionnaires using comprehensive nitrate databases. Cognition was assessed at baseline and every 18 months over a follow-up period of 126 months using a comprehensive neuropsychological test battery. Multivariable-adjusted linear mixed effect models were used to examine the association between baseline nitrate intake and cognition over the 126 months (median [IQR] follow-up time of 36 [18-72] months), stratified by APOE & epsilon;4 carrier status.Results: In non APOE & epsilon;4 carriers, for every 60 mg/day higher intake of plant-derived nitrate at baseline there was an associated higher language score [b (95% CI): 0.10 (0.01, 0.19)] over 126 months, after multivariable adjustments. In APOE e4 carriers, there was an associated better episodic recall memory [0.24 (0.08, 0.41)] and recognition memory [0.15 (0.01, 0.30)] scores. Similar associations were seen for the intakes of vegetable-derived and total nitrate. Additionally, in APOE e4 carriers, for every 6 mg/day higher intake of animal-derived nitrate (excluding meat with nitrate as an allowed additive) at baseline there was an associated higher executive function score [b (95% CI): 1.41 (0.42, 2.39)]. We did not find any evidence of an association between dietary nitrate intake and rate of cognitive decline.Conclusion: Our results suggest that habitual intake of dietary nitrate from sources where nitrate is naturally present impacts cognitive performance in an APOE genotype contingent manner. Further work is needed to validate our findings and understand potential mechanisms underlying the observed effects.& COPY; 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

This study aimed to investigate the association between dietary nitrate intake from natural sources and cognitive function and decline. The results showed that in APOE ε4 carriers, intake of vegetable-derived and total nitrate was associated with better memory. However, there was no evidence of an association between dietary nitrate intake and rate of cognitive decline.