Dataset Information

Cholesterol, statins, and dementia: what the cardiologist should know.

ABSTRACT: Alzheimer dementia (AD) is an important clinical problem that appears to be closely tied to comorbid cardiovascular disease, making it a relevant topic for the clinical cardiologist. Determinants of cardiovascular health, especially midlife dyslipidemia, are associated with an increased risk of dementia based on molecular and epidemiologic data. Given the potential role of dyslipidemia in the development of dementia, statins have been investigated as potential therapeutic options to slow or prevent disease. This review discusses the role of dyslipidemia and other cardiovascular risk factors in the pathogenesis of AD, with a focus on the existing evidence for the use of statin medications in the treatment and prevention of AD from observational studies and randomized clinical trials. Clinical questions for the practicing cardiologist are addressed.

SUBMITTER: Wanamaker BL

PROVIDER: S-EPMC4409455 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cholesterol, statins, and dementia: what the cardiologist should know.

Wanamaker Brett L BL Swiger Kristopher J KJ Blumenthal Roger S RS Martin Seth S SS

Clinical cardiology 20150413 4

Alzheimer dementia (AD) is an important clinical problem that appears to be closely tied to comorbid cardiovascular disease, making it a relevant topic for the clinical cardiologist. Determinants of cardiovascular health, especially midlife dyslipidemia, are associated with an increased risk of dementia based on molecular and epidemiologic data. Given the potential role of dyslipidemia in the development of dementia, statins have been investigated as potential therapeutic options to slow or prev ...[more]

PMID: 25869997

Similar Datasets

Project description:Obesity associated dyslipidemia and its negative effects on the heart and blood vessels have emerged as a major healthcare challenge around the globe. The use of statins, potent inhibitors of hydroxyl-methyl glutaryl (HMG) Co-A reductase, a rate-limiting enzyme in cholesterol biosynthesis, has significantly reduced the rates of cardiovascular and general mortality in patients with coronary artery disease. How statins lower plasma cholesterol levels presents a mechanistic conundrum since persistent exposure to these drugs in vitro or in vivo is known to induce overexpression of the HMG Co-A reductase gene and protein. In an attempt to solve this mechanistic puzzle, Schonewille et al, studied detailed metabolic parameters of cholesterol synthesis, inter-organ flux and excretion in mice treated with 3 common statins, rosuvastatin, atorvastatin or lovastatin, each with its unique pharmacokinetics. From the measurements of the rates of heavy water (D2O) and [13C]-acetate incorporation into lipids, the authors calculated the rates of whole body and organ-specific cholesterol synthesis in control and statin-treated mice. These analyses revealed dramatic enhancement in the rates of hepatic cholesterol biosynthesis in statin-treated mice that concomitantly elicited lower levels of cholesterol in their plasma. The authors have provided strong evidence to indicate that statin treatment in mice led to induction of compensatory metabolic pathways that apparently mitigated an excessive accumulation of cholesterol in the body. It was noted however that changes in cholesterol metabolism induced by 3 statins were not identical. While sustained delivery of all 3 statins led to enhanced rates of biliary excretion of cholesterol and its fecal elimination, only atorvastatin treated mice elicited enhanced trans-intestinal cholesterol excretion. Thus, blockade of HMGCR by statins in mice was associated with profound metabolic adaptations that reset their cholesterol homeostasis. The findings of Schonewille et al, deserve to be corroborated and extended in patients in order to more effectively utilize these important cholesterol-lowering drugs in the clinic.

Dataset Information

Cholesterol, statins, and dementia: what the cardiologist should know.

Publications

Cholesterol, statins, and dementia: what the cardiologist should know.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure