An evidence-based review of neuronal cholesterol role in dementia and statins as a pharmacotherapy in reducing risk of dementia

ABSTRACT

Introduction

Dementia is a progressive neurodegenerative disorder impairing memory and cognition. Alzheimer’s Disease, followed by vascular dementia – the most typical form. Risk factors for vascular dementia include diabetes, cardiovascular disease, hyperlipidemia. Lipids’ levels are significantly associated with vascular changes in the brain.

Areas Covered

The present article reviews the cholesterol metabolism in the brain, which includes: the synthesis, transport, storage, and elimination process. Additionally, it reviews the role of cholesterol in the pathogenesis of dementia and statin as a therapeutic intervention in dementia. In addition to the above, it further reviews evidence in support of as well as against statin therapy in dementia, recent updates of statin pharmacology, and demerits of use of statin pharmacotherapy.

Expert Opinion

Amyloid-β peptides and intraneuronal neurofibrillary tangles are markers of Alzheimer’s disease. Evidence shows cholesterol modulates the functioning of enzymes associated with Amyloid-β peptide processing and synthesis. Lowering cholesterol using statin may help prevent or delay the progression of dementia. This paper reviews the role of statin in dementia and recommends extensive future studies, including genetic research, to obtain a precise medication approach for patients with dementia.

KEYWORDS:

• Senile psychoses
• primary senile degenerative dementia
• Alzheimer type senile dementia
• Alzheimer sclerosis
• Alzheimer syndrome
• hydroxymethylglutaryl-coa reductase inhibitors
• drug therapy
• cholesterol
• amyloid-β peptide

Funding

This paper was not funded.

Article highlights

• Dementia is one of the major neurodegenerative disorders affecting Caucasians and other elderly populations.

• Abundance of cholesterol and to lesser extent amyloid beta in the brain significantly contributes to the pathophysiology of dementia.

• Decrease in cholesterol concentration or synthesis in the brain could be a therapeutic target in dementia.

• There are studies that have observed beneficial effect of statin in AD and dementia while other studies have failed to find any improvement in cognition in patients with dementia receiving statin.

• Statins and other cholesterol lowering agents should be experimented further using double-blind randomized control clinical trials with hope of finding more evidence in the prevention of dementia.

• Developing Neurological health profile for AD and aging population can help in finding precise medication approach

• To date there is not enough conclusive evidence suggesting a significant therapeutic evidence for the use of statins in prevention and treatment of dementia.

• Stem cell research and exploring genotype and phenotype of Alzheimer’s and dementia patients may help discover the appropriate drug approach to managing AD and dementia.

Acknowledgments

The authors express their gratitude to Naufela Nafisa Ahmad, Master of Arts in English Language (Linguistics), Jalan Wangsa Delima 7, Wangsa Maju, 53300 Kuala Lumpur, Malaysia, for revising and providing her expert opinion about the quality of the English language of this article.

Author contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis, and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.