Associations of Arterial Stiffness With Cognitive Performance, and the Role of Microvascular Dysfunction

Abstract

The mechanisms underlying cognitive impairment are incompletely understood but may include arterial stiffness and microvascular dysfunction. In the population-based Maastricht Study, we investigated the association between arterial stiffness and cognitive performance, and whether any such association was mediated by microvascular dysfunction. We included cross-sectional data of 2544 participants (age, 59.7 years; 51.0% men; 26.0% type 2 diabetes mellitus). We used carotid-femoral pulse wave velocity and carotid distensibility coefficient as measures of aortic and carotid stiffness, respectively. We calculated a composite score of microvascular dysfunction based on magnetic resonance imaging features of cerebral small vessel disease, flicker light-induced retinal arteriolar and venular dilation response, albuminuria, and plasma biomarkers of microvascular dysfunction (sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [von Willebrand factor]). Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the average of these domains. Higher aortic stiffness (per m/s) was associated with lower cognitive function (β, −0.018 SD [95% CI, −0.036 to −0.000]) independent of age, sex, education, and cardiovascular risk factors, but higher carotid stiffness was not. Higher aortic stiffness (per m/s) was associated with a higher microvascular dysfunction score (β, 0.034 SD [95% CI, 0.014 to 0.053]), and a higher microvascular dysfunction score (per SD) was associated with lower cognitive function (β, −0.089 SD [95% CI, −0.124 to −0.053]). Microvascular dysfunction significantly explained 16.2% of the total effect of aortic stiffness on cognitive function. The present study showed that aortic stiffness, but not carotid stiffness, is independently associated with worse cognitive performance, and that this association is in part explained by microvascular dysfunction.

Microvascular dysfunction and kidney disease: Challenges and opportunities?

“…In a recent cross‐sectional study of 2,544 patients, aortic stiffness as measured by carotid femoral pulse wave velocity was associated with cognitive dysfunction. Data showed that 16% of the effect of aortic stiffness on cognitive dysfunction was explained by microvascular dysfunction, as measured by magnetic resonance imaging, flicker light‐induced retinal arteriolar and venular dilation response, albuminuria, and plasma biomarkers of microvascular dysfunction 111 . Similar studies have shown an association between large vessel stiffness and microvascular dysfunction in the retina and kidney 112,113 .…”

Association between Very Low-Density Lipoprotein Cholesterol (VLDL-C) and Carotid Intima-Media Thickness in Postmenopausal Women Without Overt Cardiovascular Disease and on LDL-C Target Levels

“…Since subclinical atherosclerosis interfere with future clinical CVD and physical/cognitive functioning, the potential effect of modifiable health behaviors on subclinical atherosclerosis in midlife and early postmenopausal women warrants further investigation, as it may be a critical window of opportunity for prevention [31][32][33].…”

Vascular contributions to cognitive impairment and dementia (VCID): A report from the 2018 National Heart, Lung, and Blood Institute and National Institute of Neurological Disorders and Stroke Workshop

“…However, epidemiologic data clearly suggest that the potential impact of vascular risk factors on dementia may not be entirely through easily measurable vascular disease (such as stroke or small vessel disease or silent brain infarcts), or at least as limited by current technology. Microvascular dysfunction, measured using magnetic resonance imaging (MRI) as well as biomarkers of microvascular disease, only accounted for 16.2% of the effect of aortic stiffness on cognitive function, 20 white matter hyperintensities (WMH) only partially mediated the effect of hypertension on cognition, 21 and mediation analyses of other vascular risk factors have not found a clear imaging feature explaining the relationship between risk factor and cognition 22 . As technology and biomarkers of downstream vascular changes of these risk factors improves, more will be understood about the full range of mechanisms at play relating to these risk factors.…”

“…The CAIDE (Cardiovascular Risk Factors, Aging and Dementia study) risk score strongly predicted late‐life dementia, when considered in midlife, 29 and had an area under the curve of 0.74 for dementia prediction in a study of Finnish twins 30 . Life course is especially relevant because risk factors appear to be most strongly associated with adverse cognitive outcomes when considered in middle age, or perhaps even earlier: mid‐life exposure (45 to 64 years) to hypertension, smoking, and diabetes has a greater impact on dementia risk than similar risk factors in late‐life (>65 years), 17‐35 with a near‐doubling of dementia risk from midlife diabetes (hazard ratio [HR] 1.77, 95% confidence interval [CI] 1.53 to 2.04), a > 40% increased risk of dementia for midlife smokers (HR 1.41, 95% CI 1.23 to 1.61), and a similarly elevated risk for individuals with hypertension in middle age (HR 1.39, 95% CI 1.22 to 1.59), in the ARIC study, 17 with even higher estimates for more pronounced increases in blood pressure (HR 4.8, 95% CI 2.0 to 11.0 in the Honolulu Heart Program for midlife blood pressure 160 mm Hg and higher and risk of dementia) 36 …”