Do PCSK9 Inhibitors Impair Memory? A Dual Approach Combining Real-World Data and Genetic Evidence.

Abstract

Emerging evidence suggested a potential link between lipid-lowering therapies and neurocognitive effects, raising concerns regarding the possible adverse impact of PCSK9 inhibitors on memory loss. We extracted adverse events associated with memory loss for PCSK9 inhibitors from the Food and Drug Administration Adverse Event Reporting System (FAERS), covering the period from the first quarter (Q1) of 2022 to Q1 of 2025. Reporting odds ratio (ROR), Medicines and Healthcare Products Regulatory Agency (MHRA), empirical Bayesian geometric mean (EBGM), and information component (IC) were used for pharmacovigilance analysis. Drug target Mendelian randomization (MR) was utilized to assess the causal association between PCSK9 inhibitors and memory loss. A total of 389 occurrences of memory loss associated with PCSK9 inhibitors were recorded among 388 patients. In the pharmacovigilance analysis, memory loss did not show a significant signal for PCSK9 inhibitors in both the full dataset [ROR (95% CI): 0.79 (0.72, 0.88); PRR = 0.79, χ² = 20.64; EBGM05 = 0.73; IC025 = -2.00] and the lipid-lowering targets dataset [ROR (95%CI): 0.59 (0.53, 0.66); PRR = 0.59, χ² = 95.33; EBGM05 = 0.59; IC025 = -2.30]. The drug target MR revealed no causal association between PCSK9 inhibitors and memory loss (p < 0.05). The present study failed to establish a causal relationship between PCSK9 inhibitors and memory loss. By providing both real-world and genetic evidence, our findings might help alleviate concerns and support the notion that PCSK9 inhibitors were relatively safe regarding memory function.