Can
Vascular Cognitive Impairment Be Prevented?
Philip
Gorelick, Rush Medical College, Chicago, IL, USA
Vascular cognitive impairment (VCI) may
be ideally suited for prevention as it is common and thought
to be linked to several major cardiovascular risk factors
that are modifiable. The population attributable (PAR) risks
of dementia and cognitive impairment after stroke are estimated
to be about 18.4% and 8.5%, respectively. Key modifiable atherogenic
risk factor candidates for VCI include hypertension, cigarette
smoking, diabetes mellitus, hypercholesterolemia, and heavy
alcohol consumption. In addition, dietary factors such as
vitamin E, monounsaturated fats, and fish consumption may
protect against VCI. It is intriguing to note that several
traditional cardiovascular risk factors have been linked to
Alzheimer’s disease (AD). In AD, indicators of atherosclerosis
such as carotid vessel wall thickness and plaques and ankle-to-brachial
systolic blood pressure ratio, and other atherogenic factors
such as diabetes type II, atrial fibrillation, and hypertension
have been shown to be associated with risk for AD. Therefore,
it is possible that both VCI and AD are linked by similar
pathogenic mechanisms. The vascular endothelium could play
a key role in both disorders (see Vagnucci AH, Li WW, Lancet
2003; 361: 605-08, for angiogenesis hypothesis in AD). Damage
to the vascular endothelium by traditional and emerging cardiovascular
risk factors may lead to inflammation and subsequent stroke
(see Gorelick PB, Stroke 2002; 33: 862-875). Furthermore,
cerebral ischemia may upregulate the production of amyloid
precursor protein and promote its cleavage to the A-beta form
of amyloid, which can be cytotoxic to the neuron, promote
release of inflammatory mediators that worsen post-ischemic
inflammation, and cause vascular dysregulation that renders
the brain more vulnerable to injury (see Iadecola C, Gorelick
PB, Stroke 2003; 34: 335-337). VCI and AD may be synergistic
rather than just additive.
In this discussion we will review the
evidence from observational and experimental epidemiologic
studies regarding the role of various cardiovascular risk
factors that elevate risk for VCI and the outlook for prevention
of this disorder. Based on calculation of the PAR and available
clinical trial data, it is anticipated that hypertension represents
the most important modifiable risk factor target for prevention
of VCI.
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