Oral microbiome and nitric oxide biomarkers in older people with mild cognitive impairment and APOE4 genotype

L'Heurreux, Joanna, Corbett, Anne, Ballard, Clive, Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756, Creese, Byron, Winyard, Paul G., Jones, Andrew M. and Vanhatalo, Anni (2024) Oral microbiome and nitric oxide biomarkers in older people with mild cognitive impairment and APOE4 genotype. PNAS Nexus. ISSN 2752-6542 (In Press)

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Abstract

Apolipoprotein E4 (APOE4) genotype and nitric oxide (NO) deficiency are risk factors for age-associated cognitive decline. The oral microbiome plays a critical role in maintaining NO bioavailability during ageing. The aim of this study was to assess interactions between the oral microbiome, NO biomarkers and cognitive function in 60 participants with mild cognitive impairment (MCI) and 60 healthy controls using weighted gene co-occurrence network analysis (WGCNA), and to compare the oral microbiomes between APOE4 carriers and non-carriers in a subgroup of 35 MCI participants. Within the MCI group, a high relative abundance of Neisseria associated with better indices of cognition relating to executive function (Switching Stroop, rs=0.33, p=0.03) and visual attention (Trail Making, rs=-0.30, p=0.05), and in the healthy group Neisseria correlated with working memory (Digit Span, rs=0.26, p=0.04). High abundances of Haemophilus (rs=0.38, p=0.01) and H. parainfluenzae (rs=0.32, p=0.03), that co-occurred with Neisseria, correlated with better scores on executive function (Switching Stroop) in the MCI group. There were no differences in oral nitrate (p=0.48) or nitrite concentrations (p=0.84) between the MCI and healthy groups. Linear discriminant analysis Effect Size (LEfSe) identified Porphyromonas as a predictor for MCI and Prevotella intermedia as a predictor of APOE4-carrier status. The principal findings of this study were that a greater prevalence of oral P. intermedia is linked to elevated genetic risk for dementia (APOE4 genotype) in individuals with MCI prior to dementia diagnosis, and that interventions that promote the oral Neisseria-Haemophilus and suppress Prevotella-dominated modules have potential for delaying cognitive decline.

Item Type:	Article
Uncontrolled Keywords:	cognitive status,ageing,nitrate,prevotella,genetic risk,sdg 3 - good health and well-being,3* ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Depositing User:	LivePure Connector
Date Deposited:	22 Jan 2025 01:04
Last Modified:	22 Jan 2025 01:04
URI:	https://ueaeprints.uea.ac.uk/id/eprint/98288
DOI:	issn:2752-6542

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