A review on the efficacy and safety of lipid-lowering drugs in neurodegenerative disease

Abstract

There is a train of thought that lipid therapies may delay or limit the impact of neuronal loss and poor patient outcomes of neurodegenerative diseases (NDDs). A variety of medicines including lipid lowering modifiers (LLMs) are prescribed in NDDs. This paper summarizes the findings of clinical and observational trials including systematic reviews and meta-analyses relating to LLM use in NDDs published in the last 15 years thus providing an up-to-date evidence pool. Three databases were searched PubMed, CINAHL, and Web of Science using key terms relating to the review question. The findings confirm the benefit of LLMs in hyperlipidemic patients with or without cardiovascular risk factors due to their pleotropic effects. In NDDs LLMs are proposed to delay disease onset and slow the rate of progression. Clinical observations show that LLMs protect neurons from α-synuclein, tau, and Aβ toxicity, activation of inflammatory processes, and ultimately oxidative injury. Moreover, current meta-analyses and clinical trials indicated low rates of adverse events with LLMs when used as monotherapy. LLMs appear to have favorable safety and tolerability profiles with few patients stopping treatment due to severe adverse effects. Our collated evidence thus concludes that LLMs have a role in NDDs but further work is needed to understand the exact mechanism of action and reach more robust conclusions on where and when it is appropriate to use LLMs in NDDs in the clinic.

Causal relationship between PCSK9 inhibitor and common neurodegenerative diseases: A drug target Mendelian randomization study

“…Therefore, dyslipidemia may be associated with the development and progression of neurodegenerative diseases. There were some evidence suggested that lipid‐lowering drugs have an impact on neurodegenerative diseases (Rajabian et al., 2023 ). For example, Statin therapy was reported to associate with decreased development of AD (Lee et al., 2020 ).…”