Beyond Lipid-Lowering and Stroke Prevention: Unraveling the Role of Statins in Neurological Diseases

Background: Statins are established therapies for reducing cardiovascular and cerebrovascular risk. Beyond their lipid-lowering effects, they exert pleiotropic actions, including anti-inflammatory, immunomodulatory, antioxidant, anti-apoptotic, and vascular effects. Methods: This narrative review explores the effects of statins in a range of characteristic neurological disorders beyond stroke prevention, encompassing migraine, neurodegenerative and neuroinflammatory diseases, myasthenia gravis (MG), traumatic brain injury (TBI), brain tumors, epilepsy, and peripheral neuropathy (PN). A literature search was conducted in PubMed, Embase, and Scopus, focusing on proposed mechanisms of action, clinical outcomes, and potential neurological adverse effects. Results: Research suggests potential benefits of statins in migraine, TBI and its complications, brain tumors, and epilepsy. Favorable findings have also been reported in neurodegenerative and neuroinflammatory conditions, including Parkinson’s disease, Huntington’s disease, and multiple sclerosis. Despite earlier concerns regarding a possible association between statin use and an increased risk of dementia, subsequent studies have challenged this association, with some suggesting even a protective effect. Potential neurological adverse effects also warrant attention, particularly the reported association between statin exposure and new-onset or worsening MG. In contrast, data linking statin use to amyotrophic lateral sclerosis and PN are controversial and do not support causality. Interpretation of the available findings is complicated by heterogeneity in statin type and lipophilicity, dosage, treatment duration, disease stage, and study design. Clinical evidence is derived predominantly from observational studies, which are susceptible to confounding and other methodological limitations. Randomized controlled trials remain relatively few, with some further limited by small sample sizes. Conclusions: The pleiotropic properties of statins provide a rationale for investigating their potential therapeutic role across a broad spectrum of neurological disorders. Nevertheless, the available evidence remains heterogeneous and, in several conditions, conflicting. Further adequately powered randomized controlled trials are needed to establish whether statins translate their proposed pleiotropic effects into clinically meaningful benefits in specific neurological disorders and to better characterize their potential neurological risks.