Statins in the prevention and treatment of Alzheimer disease.
Vascular risk factors such as hypertension and hypercholesterolemia during midlife increase the risk for Alzheimer's disease (AD). Treatment of hypercholesterolemia and other vascular risk factors may have great implications in the prevention of AD. Recent findings illustrate that the sterol metabolism in the brain is an active process, well controlled and regulated by 24-hydroxylase, an enzyme that is uniquely expressed in the brain. The use of statins in ischemic heart disease (IHD) has proven to be a phenomenal advance in pharmacological disease prevention and treatment. A growing body of evidence, suggest that statins exhibit additional benefits that are independent of their cholesterol-lowering actions. Statin treatment has also considerable effect in prevention of ischemic stroke. In animal models of ischemic stroke, statins have proven to reduce infarct size through up-regulation of endothelial nitric oxide synthases. Data from recent observational studies have revealed a potential role for statins in prevention of AD. The following review comments the processes leading to dementia including the involvement of cholesterol regulation, cerebral circulation and inflammation in development of dementia. The mechanisms by which statins may be beneficial in controlling these processes is discussed.
Crisby
Milita
M
The Alzheimer Disease Research Center, Karolinska Institute, Neurotec Division of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden. milita.crisby@neurotec.ki.se
Carlson
Lars A
LA
Winblad
Bengt
B
D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000209:etiology; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy; D012307:Risk Factors; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors