Hypertension-related risk for dementia: A summary review with future directions.

Chronic hypertension, or high blood pressure, is the most prevalent vascular risk factor that accelerates cognitive aging and increases risk for Alzheimer's disease and related dementia. Decades of observational and clinical trials have demonstrated that midlife hypertension is associated with greater gray matter atrophy, white matter damage commiserate with demyelination, and functional deficits as compared to normotension over the adult lifespan. Critically, hypertension is a modifiable dementia risk factor: successful blood pressure control with antihypertensive treatment improves outcomes as compared to uncontrolled hypertension, but does not completely negate the risk for dementia. This suggests that hypertension-related risk for neural and cognitive decline in aging cannot be due to elevations in blood pressure alone. This summary review describes three putative pathways for hypertension-related dementia risk: oxidative damage and metabolic dysfunction; systemic inflammation; and autonomic control of heart rate variability. The same processes contribute to pre-clinical hypertension, and therefore hypertension may be an early symptom of an aging nervous system that then exacerbates cumulative and progressive neurodegeneration. Current evidence is reviewed and future directions for research are outlined, including blood biomarkers and novel neuroimaging methods that may be sensitive to test the specific hypotheses.