Inter‐Relations of Orthostatic Blood Pressure Change, Aortic Stiffness, and Brain Structure and Function in Young Adults

BACKGROUND: Relations of orthostatic change in blood pressure with brain structure and function have not been studied thoroughly, particularly in younger, healthier individuals. Elucidation of factors that contribute to early changes in brain integrity may lead to development of interventions that delay or prevent cognitive impairment. METHODS AND RESULTS: In a sample of the Framingham Heart Study Third Generation (N=2119; 53% women; mean age±SD, 47±8 years), we assessed orthostatic change in mean arterial pressure (MAP), aortic stiffness (carotid‐femoral pulse wave velocity), neuropsychological function, and markers of subclinical brain injury on magnetic resonance imaging. Multivariable regression analyses were used to assess relations between orthostatic change in MAP and brain structural and neuropsychological outcomes. Greater orthostatic increase in MAP on standing was related to better Trails B‐A performance among participants aged <49 years (β±SE, 0.062±0.029; P=0.031) and among participants with carotid‐femoral pulse wave velocity <6.9 m/s (β±SE, 0.063±0.026; P=0.016). This relation was not significant among participants who were older or had stiffer aortas. Conversely, greater orthostatic increase in MAP was related to larger total brain volume among older participants (β±SE, 0.065±0.029; P=0.023) and among participants with carotid‐femoral pulse wave velocity ≥6.9 m/s (β±SE, 0.078±0.031; P=0.011). CONCLUSIONS: Blunted orthostatic increase in MAP was associated with smaller brain volume among participants who were older or had stiffer aortas and with poorer executive function among persons who were younger or who had more‐elastic aortas. Our findings suggest that the brain is sensitive to orthostatic change in MAP, with results dependent on age and aortic stiffness.