Decreased Peripheral Endothelial Function is Associated with Mild Cognitive Impairment and Lower Performance on Memory and Language

AbstractBackgroundThe association between cardiovascular risk factors and cognitive decline is known, but the underlying mechanisms remain unclear. We investigated whether peripheral microvascular and endothelial function, measured by pulsatile arterial tonometry (EndoPAT), is associated with cognitive performance and mild cognitive impairment (MCI).MethodThis study is based on data from 340 participants (150 with MCI, 190 with normal cognition (NC); mean age 64.9 (SD: 7.7) years, 61% female, 48% African American) enrolled in the VAScular ContribUtors to prodromaL AlzheimeR’s disease (VASCULAR) study. Peripheral microvascular function was assessed using EndoPAT (Itamar Inc.), and a reactive hyperemic index (RHI) was derived after a 5‐minute arterial occlusion period and includes a continuous or discrete (dichotomous or tertile) variable. Cognitive assessment and diagnostic categorization performed at the baseline visit included Montreal Cognitive Assessment (MoCA), Boston Naming Test, Hopkins Verbal Learning Test‐Revised (HVLT‐R), and Trail Making Test. Groups were compared with a t‐test and multivariable logistic and linear regression analyses were performed to adjust for demographic and risk factor covariates.ResultParticipants with MCI had lower RHI, indicative of greater peripheral microvascular and endothelial dysfunction, compared to NC (mean 1.9 (SD: 1.4) vs 2.2 (0.7) AU, p=0.014), which remained significant after adjustment for age, education, sex, race, systolic blood pressure, history of diabetes, hyperlipidemia, and smoking (OR: 3.91 for each 1‐unit change in RHI (95% CI: 1.00, 7.08), p=0.03). When analyzed in tertiles, a lower RHI (<1.75 AU) was also associated with poorer expressive language (Boston Naming Test, p=0.03), and verbal memory performance (HVLT‐R delayed recall, p=0.01; HVLT‐R retention, p=0.02). Executive function (Trail Making Test) and overall cognitive status (MoCA) were not significantly associated with RHI.ConclusionPeripheral microvascular endothelial dysfunction, measured as RHI, was associated with MCI and with lower performances on measures of language and memory. These data highlight the importance of systemic microvascular health in cognitive health. Strategies targeting microvascular endothelial function may need further investigation in cognitive therapeutics.