Associations of brain structure and neuropsychological function with artificial intelligence estimates of biologic vascular age

Abstract

Background: Accelerated vascular aging, assessed as artificial intelligence-based vascular age (AIVA), is associated with small vessel disease that may impact brain structure and neuropsychological function. Methods: In a cross-section of Framingham Heart Study participants, AIVA was estimated using a validated convolutional neural network trained to predict carotid-femoral pulse wave velocity from a normalized pressure waveform. Brain structure was assessed using MRI with diffusion tensor imaging, and neuropsychological function was assessed via a standardized test battery. Analyses included MRI (N=2313) and neuropsychological (N=3001) samples. We used multivariable linear and logistic regression to relate AIVA with brain structural and neuropsychological functional measures. Results: The mean±SD age across participants was 62±11 years; 56% were women. In multivariable models, higher AIVA was associated with worse markers of cerebral small vessel disease (mean white matter free water: β [per SD], 0.09; 95% CI, 0.04 to 0.14; P<0.001; peak width of skeletonized mean diffusivity: β, 0.05; 95% CI, 0.00 to 0.10; P=0.045; white matter hyperintensity volume: β, 0.08; 95% CI, 0.03 to 0.12; P<0.001) and higher odds of cerebrovascular injury (presence of extensive white matter hyperintensities: OR [per SD]=1.22; 95% CI, 1.02 to 1.47; P=0.03; presence of brain infarcts: OR=1.44; 95% CI, 1.02 to 2.04; P=0.04). Additionally, higher AIVA was associated with worse performance on trails B-A (β, −0.05; 95% CI, −0.10 to −0.01; P=0.03), similarities (β, −0.06; 95% CI, −0.11 to −0.01; P=0.02), and global cognition (β, −0.07; 95% CI, −0.12 to −0.03; P=0.002) and higher odds of prevalent depressive symptoms (OR=1.24; 95% CI, 1.08 to 1.41; P=0.002) and high CES-D score (OR=1.20; 95% CI, 1.00 to 1.44; P=0.047). Vascular brain injury markers partially mediated relations of AIVA with global cognition score and presence of depressive symptoms. Conclusion: Peripheral pressure waveform AIVA may be a novel, noninvasive indicator of subclinical vascular brain injury and neuropsychological function.