Abstract

Introduction: Cardiovascular disease (CVD) and Alzheimer’s Dementia (AD) share numerous risk factors, with vascular dysfunction a common underlying mechanism. Individuals with mild cognitive impairment (MCI) have a high likelihood of developing AD in their lifetime. The link between microvascular dysfunction (MVD) and AD has yet to be fully established. Hypothesis: We examined the contribution of MVD to MCI with the hypothesis that Black Americans, who have a higher prevalence of MVD, will have higher rates of MCI. Methods: Participants >50 years with MCI or with normal cognition (NC) were enrolled for neuropsychological and microvascular function testing using peripheral arterial tonometry. Microvascular function was measured as the reactive hyperemia index (RHI) and calculated as the ratio of the post- to pre-occlusion pulse volume in the fingertip (EndoPAT). Multivariate analyses, adjusting for demographic and CVD risk factors associated with MCI, evaluated the relationship between RHI and MCI in Black and White participants. Causal mediation analysis, using the Monte Carlo approach, was performed to investigate whether the effect of RHI on MCI was mediated through plausible mediators, including risk factors. Results: Of 152 participants (NC=104, MCI=48), 41.4% were Black and 33.6% male. Participants with MCI were more likely to be Black (58.3% vs 33.7%%, p=0.007) and have lower RHI (1.93 vs 2.27, p=0.004) compared to NC. RHI was an independent predictor of MCI with a 96% adjusted greater odds of MCI per unit reduction in RHI. Black race remained an independent predictor of MCI (OR 2.90, 95% CI [1.16, 7.56]). RHI was lower in Black compared to White participants (1.86 vs 2.37, p<0.001). There was no heterogeneity in the impact of RHI on MCI. In a casual mediation analysis, MCI was mediated via RHI more in Black than in White participants (proportion mediated 24.2% vs 18.4%, p=0.034) after multivariate adjustment. Conclusions: Peripheral MVD, measured as RHI, was independently associated with MCI. Furthermore, Black participants exhibited lower RHI levels, a higher prevalence of MCI, and potentially mediated MCI through RHI to a greater extent compared to their White counterparts.

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