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Loss of cognitive function and hypertension are two common conditions in the elderly and both significantly contribute to loss of personal independency. Microvascular brain damage – the result of age-associated alteration in large arteries and the progressive mismatch of their cross-talk with small cerebral arteries – represents a potent risk factor for cognitive decline and for the onset of dementia in older individuals. The present review discusses the complexity of factors linking large artery to microvascular brain disease and to cognitive decline and the evidence for possible clinical markers useful for prevention of this phenomenon. The possibility of dementia prevention by cardiovascular risk factors control has not been demonstrated. In the absence of research clinical trials specifically and primarily designed to demonstrate the antihypertensive treatment efficacy for reducing the risk of dementia, further evidence demonstrating that it is possible to limit the progression of microvascular brain damage is needed.