Baseline habitual dietary nitrate intake and Alzheimer's Disease related neuroimaging biomarkers in the Australian Imaging, Biomarkers and Lifestyle study of ageing - 12/04/25

Doi : 10.1016/j.tjpad.2025.100161

Anjana Rajendra ^a, Nicola P. Bondonno ^a,^b, Kevin Murray ^c, Liezhou Zhong ^a, Stephanie R. Rainey-Smith ^d,^e,^f,^g,^h, Samantha L. Gardener ^e,^f,^g, Lauren C. Blekkenhorst ^a,^q, Vincent Doré ^i,^j, Victor L. Villemagne ^j,^k,^l, Simon M. Laws ^l,^m,ⁿ, Belinda M. Brown ^d,^e,^m, Kevin Taddei ^f, Colin L. Masters ^o, Christopher C. Rowe ^j,^o, Ralph N Martins ^f, Jonathan M. Hodgson ^a,^p, Catherine P. Bondonno ^a,^p,^⁎
For the
AIBL Research Group^q
^a Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia
^b The Danish Cancer Institute, Copenhagen, Denmark
^c School of Population and Global Health, University of Western Australia, Perth, Western Australia, Australia
^d Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Murdoch, Western Australia, Australia
^e Lifestyle Approaches Towards Cognitive Health Research Group, Murdoch University, Murdoch, Western Australia, Australia
^f Centre of Excellence for Alzheimer's Disease Research & Care, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia
^g Australian Alzheimer's Research Foundation, Nedlands, Western Australia, Australia
^h School of Psychological Science, University of Western Australia, Perth, Western Australia, Australia
ⁱ Australian E-Health Research Centre, CSIRO, 351 Royal Parade, Parkville, Victoria, Australia
^j Department of Molecular Imaging and Therapy, Austin Health, 145 Studley Road, Heidelberg, Victoria, Australia
^k Department of Psychiatry, University of Pittsburgh, Thomas Detre Hall, 3811 O'Hara Street, Pittsburgh, PA, USA
^l Centre for Precision Health, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, Australia
^m Collaborative Genomics and Translation Group, Edith Cowan University, 270 Joondalup Drive, Joondalup, Western Australia, Australia
ⁿ Curtin Medical School, Curtin University, Kent Street, Bentley, Western Australia, Australia
^o The Florey Institute, The University of Melbourne, Parkville, Victoria, Australia
^p Medical School, The University of Western Australia, Royal Perth Hospital Research Foundation, Perth, Western Australia, Australia
^q For a full list of the AIBL Research Group see aibl.org.au

^⁎Corresponding author at: Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Level 3, Royal Perth Hospital Research Foundation. Rear 50 Murray St, Perth, Western Australia, Australia WA 6000.Nutrition & Health Innovation Research InstituteSchool of Medical and Health SciencesEdith Cowan UniversityLevel 3, Royal Perth Hospital Research Foundation. Rear 50 Murray St, Perth, Western AustraliaWA6000Australia

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Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Saturday 12 April 2025

Abstract

Background

Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia.

Objective

Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD).

Participants

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.

Methods

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.

Results

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.

Conclusions

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.

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Keywords : Nitrate, Alzheimer's disease, Dementia, Cerebral beta-amyloid, Diet, Apoe, Neuroimaging brain biomarkers, Brain atrophy

Plan

Baseline characteristics

Longitudinal analyses of source-specific nitrate intake and AD-related neuroimaging biomarkers of brain health

Discussion

Conclusion

CRediT authorship contribution statement

	Data described in the manuscript, code book, and analytic code will be made available upon request pending approval of an Expression of Interest submitted to the AIBL Study Scientific Management Committee.
	Disclaimers: None.