Epidemiological findings of vascular risk factors in Alzheimer's disease: implications for therapeutic and preventive intervention.

Alzheimer's disease (AD) is a multifactorial disorder, in which the detrimental effects of vascular risk factors and related disorders (e.g., smoking, obesity, hypertension, diabetes, dyslipidemia and inflammation) have been frequently suggested in numerous observational studies of the general population. In recent years, systematic reviews and meta-analyses of population-based prospective studies have concluded from the life-course perspective, an age-dependent association with the risk of AD for several vascular factors, such as high blood pressure, obesity and high total cholesterol, such that possessing these factors in midlife is associated with an increased risk of late-life AD, whereas having a low level in late life or a decline after middle age in these factors may anticipate clinical onset of AD. The biological plausibility for these vascular factors and related disorders being involved in the pathogenesis and clinical manifestation of AD is also supported by population-based neuroimaging and neuropathological studies. However, randomized placebo-controlled trials that target those major cardiovascular risk factors (e.g., antihypertensive, hormone replacement and anti-inflammatory therapies) have generally failed to prove to be efficacious preventive or therapeutic approaches for AD. The multifactorial nature of AD and the age-dependent relationship between vascular risk factors and the risk of AD should be taken into consideration in the future when designing preventive or therapeutic intervention against the dementing disorder.