Association of arterial stiffness with progression of subclinical brain and cognitive disease

Objective: We tested whether abnormal arterial stiffness and blood pressure would be associated with progression of brain aging measured by brain MRI and neurocognitive testing. Methods: Framingham Offspring Cohort participants (n = 1,223, 61 +/- 9 years, 56% women) without previous stroke or dementia underwent applanation tonometry, brain MRI, and neurocognitive testing at examination 7 (1998-2001). Follow-up brain MRI and neurocognitive testing was performed at examination 8 (2005-2008, mean interval 6.4 +/- 1.3 years). We related examination 7 inverse-transformed carotid-femoral pulse wave velocity (iCFPWV), central pulse pressure (CPP), and mean arterial pressure to changes in the following variables between examinations 7 and 8: total cerebral brain volume, white matter hyperintensity volume, and performance on executive function and abstraction tasks, the Trail Making Test, Parts B and A (Delta Trails B-A), and Similarities tests. Results: Higher baseline iCFPWV and CPP were associated with greater progression of neurocognitive decline (iCFPWV and Delta Trails B-A association: SD unit change in outcome variable per SD change in tonometry variable [beta] +/- SE = 0.10 +/- 0.04, p = 0.019; CPP and Delta Similarities association: -0.08 +/- 0.03, p = 0.013). Higher mean arterial pressure, but not iCFPWV or CPP, was associated with increase in white matter hyperintensity volume ([beta +/- SE] 0.07 +/- 0.03, p = 0.017). No tonometry measures were associated with change in cerebral brain volume. Conclusions: In middle-aged and older adults without evidence of clinical stroke or dementia, elevated arterial stiffness and pressure pulsatility are associated with longitudinal progression of subclinical vascular brain injury and greater neurocognitive decline. Treatments to reduce arterial stiffness may potentially reduce the progression of neurovascular disease and cognitive decline.