Neurocognitive Impairment in Cardiovascular Disease Patients Taking Statins Versus Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: A Systematic Review

Abstract

Cardiovascular diseases (CVDs) are prevalent medical conditions affecting millions of people worldwide and are associated with significant morbidity and mortality. The main precursor of CVDs and the related events, such as hypertension and heart failure, is hyperlipidemia, most commonly an increase in low-density lipoproteins. Lipid-lowering drugs are cardinal in the treatment of CVDs. American College of Cardiology and American Heart Association have issued guidelines for lipid-lowering therapy, and statins are first-line medication. In the recent years, a new class of lipid-lowering agents called proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has been identified as the potential lipid-lowering therapy for the statin-resistant patient. In clinical trials and observational studies, PCSK9 inhibitors and statins are both associated with the development of neurocognitive dysfunction in the older population. This systematic review aims to inquire if there is significant neurocognitive dysfunction associated with statins and PCSK9 inhibitors and compare neurocognitive effects associated with statins with those of PCSK9 inhibitors.

Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence

“…Neurocognitive adverse events have been observed in the use of LDL‐C lowering HMG‐CoA reductase inhibitors, which has been recognized that lowering LDL‐C is a key incentive in neuronal cell dysfunction (Shahid et al, 2022; Yuet et al, 2021). The main objective of this review article is to describe the effect of different PCSK9 levels (PCSK9 gene mutations and PCSK9 inhibitors) on neurocognitive adverse events through population samples.…”

“…An early study had showed that the overexpression of neural apoptosis‐regulated convertase 1 (NARC‐1) gene, PCSK9, enhanced the recruitment of undifferentiated neural telencephalic progenitor cells toward the neuronal lineage, thus PCSK9 inhibition may affect the development of neurological disorders from this perspective (Seidah et al, 2003). Glucose metabolism disorder, N‐methyl‐ D ‐aspartic acid receptor regulation, and genetic variation have also been reported as susceptibility risk factors leading to neurological dysfunction and allow PCSK9 inhibitors to enter the brain (Shahid et al, 2022).…”

Ups and downs in PCSK9 inhibition in the cardiovascular arena: a review

“…No increased risk of serious adverse events, including neurocognitive effects, gastrointestinal hemorrhage, cataracts, new onset diabetes mellitus, or myalgias were found [47]. In addition, specific analyses of neurocognition [48][49][50][51][52], including studies [53,54] that performed serial assessment using a formal standardized tool [55], did not find any relationship between PCSK9i or achieved LDL-C and adverse neurocognitive function.…”