Evidence and mechanisms for statin-induced cognitive decline

ABSTRACT

Introduction: Statin drugs have become the most highly prescribed drugs for cardiovascular disease. However, there is disagreement as to the existence of adverse effects of statin administration on cognitive function. Therefore, it is important to better understand the effects of statins on cognition and possible mechanisms of these effects.

Areas covered: We analyzed relevant studies of the relationship between cognitive performance and statin and usage. We included articles published between 2018 and 1992. We identified three randomized trials, one observational study and 66 case reports that provided credible evidence of statin-induced cognitive impairment. We also identified seven randomized trials and two observational studies reporting no significant evidence of statin-induced cognitive impairment.

Expert opinion: We found methodological differences that may have contributed to the divergence of these results. Evaluation of all these studies indicated that statin-associated cognitive decline is a real entity. Likely mechanisms to explain the adverse effects include 1. Reduction of synthesis of coenzyme Q₁₀ with consequent increasing oxidative stress and reduction of cerebral energy production; 2. Depletion of central nervous system myelin by inhibition of cholesterol synthesis. We conclude that statin-induced cognitive decline does exist, needs to be better recognized and requires more studies of prevention and treatment.

KEYWORDS:

• Biological mechanisms
• cardiovascular disease
• Coenzyme Q₁₀
• cognitive decline
• HMG-CoA
• side-effects
• statins

Article highlights

• Although uncommon, statin-associated cognitive decline does exist.

• Most of the studies that could not detect cognitive decline had methodological shortcomings, either being underpowered or by lacking in high-quality cognitive assessment techniques.

• Possible mechanisms of statin-induced cognitive decline include oxidative stress and mitochondrial dysfunction due to CoQ10 deficiency, and demyelination of the central nervous system.

• Neurological side effects of statins need to be recognized, prevented, and treated.

Declaration of interest

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.