Oral microbiome and nitric oxide biomarkers in older people with mild cognitive impairment and <i>APOE4</i> genotype

Apolipoprotein <i>E4</i> (<i>APOE4</i>) 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 aging. 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 and to compare the oral microbiomes between <i>APOE4</i> carriers and noncarriers in a subgroup of 35 MCI participants. Within the MCI group, a high relative abundance of <i>Neisseria</i> was associated with better indices of cognition relating to executive function (Switching Stroop, <i>r_s</i> = 0.33, <i>P</i> = 0.03) and visual attention (Trail Making, <i>r_s</i> = -0.30, <i>P</i> = 0.05), and in the healthy group, <i>Neisseria</i> correlated with working memory (Digit Span, <i>r_s</i> = 0.26, <i>P</i> = 0.04). High abundances of <i>Haemophilus</i> (<i>r_s</i> = 0.38, <i>P</i> = 0.01) and <i>Haemophilus parainfluenzae</i> (<i>r_s</i> = 0.32, <i>P</i> = 0.03), that co-occurred with <i>Neisseria</i> correlated with better scores on executive function (Switching Stroop) in the MCI group. There were no differences in oral nitrate (<i>P</i> = 0.48) or nitrite concentrations (<i>P</i> = 0.84) between the MCI and healthy groups. Linear discriminant analysis Effect Size identified <i>Porphyromonas</i> as a predictor for MCI and <i>Prevotella intermedia</i> as a predictor of <i>APOE4</i>-carrier status. The principal findings of this study were that a greater prevalence of oral <i>P. intermedia</i> is linked to elevated genetic risk for dementia (<i>APOE4</i> genotype) in individuals with MCI prior to dementia diagnosis and that interventions that promote the oral <i>Neisseria-Haemophilus</i> and suppress <i>Prevotella</i>-dominated modules have potential for delaying cognitive decline.