Arterial stiffness, cognition, and type 2 diabetes mellitus – preliminary results from The Maastricht Study

Stefan LC Geijselaers, Simone JS Sep, Miranda T Schram, Martin van Boxtel, Annemarie Koster, Bram A Kroon, Nicolaas C Schaper, Ronald MA Henry, Coen DA Stehouwer, Geert Jan Biessels

Background:
Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and dementia. The aetiology of these cerebral complications is considered multifactorial and may include vascular changes. Arterial stiffening has been increasingly associated with cognitive dysfunction, most likely via increased pulsatile load on the brain microvasculature, but its role in the relationship between T2DM and cognitive functioning is currently unknown.

Methods:
Cross-sectional regression analyses were performed in 669 participants from The Maastricht Study (mean age 59±8 years, 55% men, 183 with T2DM) who completed an extensive neuropsychological test battery to assess cognitive functioning. Carotid-femoral pulse wave velocity (cfPWV) and local indices of carotid stiffness (n=623) were evaluated as markers of arterial stiffness.

Results:
After adjustment for age, sex, and educational level, the results showed that lower carotid distensibility (CarDC) and compliance (CarCC) were associated with worse cognitive performance, whereas carotid Young’s elastic modulus (CarYEM) and cfPWV were not. The following domains were affected: global cognition (standardised regression coefficient for CarDC -0.08, p=0.03), processing speed (CarCC -0.08, p=0.04), and executive function and attention (CarDC -0.11, p=0.01; CarCC -0.08, p=0.04). A trend was observed between lower CarDC and worse information processing speed (-0.07, p=0.10). Additional adjustment for mean arterial pressure and heart rate, as well as further adjustment for traditional cardiovascular risk factors and depression, did not materially alter these associations. Overall, greater arterial stiffness was not associated with impaired memory function. Individuals with T2DM performed worse in all cognitive domains (mean differences of z-scores ranged from -0.20 to -0.155, p<0.05) and had higher cfPWV (mean difference (95% CI) 0.40 m/s (0.04;0.77)). Carotid stiffness did not significantly differ between individuals with and without T2DM: CarDC -0.01 10-3/kPa (-0.89;0.86); CarCC -0.02 mm2/kPa (-0.08;0.03); CarYEM -4E-3 103/kPa (-0.08;0.07). The associations between T2DM and cognitive functioning did not change after adjustment for CarDC, CarCC, or CarYEM (change in regression coefficient of T2DM ranged from 0.58 to 4.64%).

Conclusion:
The present study shows that carotid artery stiffness is associated with cognitive performance, but does not mediate the relationship between T2DM and cognitive dysfunction.