Tag: statins

Statins not Associated With Cognitive Decline

Photo by Matteo Vistocco on Unsplash

A new study has found that statin use in adults 65 years old or older is not associated with incident dementia, mild cognitive impairment (MCI) or decline in individual cognition domains.

Major health concerns in the elderly, cognitive decline and dementia affect about 10% of people over 60 years old. Statins are used to reduce low-density lipoprotein cholesterol, and are a fundamental treatment for prevention of primary and secondary cardiovascular disease (CVD) events. 
In 2012 the Food and Drug Administration issued a warning about cases of apparent short-term cognitive impairment with statin use, while acknowledging that the cardiovascular benefits outweigh their risks. Systematic reviews have since shown insufficient evidence on the impact of statins, and research has shown mixed results, with some showing a neurocognitive benefit of statins and others reporting a null effect.

“With statins being increasingly prescribed to older adults, their potential long-term effects on cognitive decline and dementia risk have attracted growing interest,” said lead author Zhen Zhou, PhD, Menzies Institute for Medical Research at the University of Tasmania. “The present study adds to previous research by suggesting that statin use at baseline was not associated with subsequent dementia incidence and long-term cognitive decline in older adults.”

Researchers of this study analysed data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. ASPREE was a large prospective, randomized placebo-controlled trial of daily low-dose aspirin with adults 65 or older. One of the key selection criteria of ASPREE was that participants had to have a score of 78 for the Modified Mini-Mental State Examination test, a screening test for cognitive abilities, at enrollment.

The study had 18 846 participants, grouped by their baseline statin use (31.3% of participants) versus non-statin use. The study aimed to measure outcomes including incident dementia and its subclassifications (probable Alzheimer’s disease [AD], mixed presentations); MCI and its subclassifications (MCI consistent with AD, MCI-other); changes in domain-specific cognition including global cognition, memory, language and executive function, and psychomotor speed; and in the composite of these domains.

After a median of 4.7 years of follow-up, researchers found 566 incident cases of dementia (including probable AD and mixed presentations). Compared with no statin use, statin use was not associated with risk of all-cause dementia, probable AD or mixed presentations of dementia. There were 380 incident cases of MCI found (including MCI consistent with AD and MCI-other). Compared to no statin use, statin use was not associated with risk of MCI, MCI consistent with AD or other MCI. No statistically significant difference in the change of composite cognition and any individual cognitive domains between statin users versus non-statin users was seen. However, researchers did find interaction effects between baseline cognitive ability and statin therapy for all dementia outcomes.

The researchers acknowledged several limitations, including observational study bias and lack of data on the length of prior use of statins; and the dose of statins was not recorded in the ASPREE trial, so their effects could not be fully explored. Researchers conclude the study must be interpreted with caution and will require confirmation by randomized clinical trials designed to explore the neurocognitive effects of statins in older populations.

In an accompanying editorial comment, Christie M. Ballantyne, MD, professor at Baylor College of Medicine in Houston, noted study limitations that the authors address, but agreed the findings suggest statins do not contribute to cognitive decline.

“Overall, the analysis was well done, and its main strengths are a large cohort with a battery of standardised tests that allowed the investigators to track both cognition and incidence of dementia and its subtypes over time,” Ballantyne said. “Lingering questions such as the one raised by this analysis regarding potential adverse effects of statins in individuals with mildly impaired cognition can only be answered in randomised controlled trials in the appropriate age group and population and with appropriate testing and adequate follow-up. In the meantime, practising clinicians can have confidence and share with their patients that short-term lipid lowering therapy in older individuals, including with statins, is unlikely to have a major impact on cognition.”

Source: American College of Cardiology

Simvastatin Treatment Hope for Subtype of Ovarian Cancer

Researchers have found that simvastatin has anti-proliferative potential against ovarian clear cell carcinoma, a highly lethal gynaecological cancer.

Dr Ingrid Hedenfalk from The Lund University explained: “Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) accounting for 5–10% of cases diagnosed in Europe and America, while the incidence in Asia is reported to be higher (10–20%).”

GTPases are a range of enzymes that hydrolyse guanosine triphosphate (GTP) to guanosine diphosphate (GDP). They are also involved in cells as switches and timers. Rho GTPases have been studied for their role in cancers. However, it is difficult to target Rho GTPases directly, so research has involved indirect strategies.

The researchers tested three cell lines of OCCC and one line of high-grade serous ovarian carcinoma (HGSOC) with simvastatin, which is a Rho GTPase interfering drug, and another GTPase interfering drug, CID-1067700, as a control. CID-1067700 is a pan-GTPase, which makes it useful as a comparator.

The research was motivated by a study which found deregulated expression of both Rho GTPases and cytoskeletal pathways in primary human OCCC tumours. The OCCC cell lines treated with simvastatin showed reduced c-Myc protein expression and signs of cell death, as well as curbing proliferation and migration.

Simvastatin could act through Rho GTPase interference as simvastatin affects the cytoskeletal integrity of OCCC cells at clinically relevant levels. However, the mechanism involved is different from Rho GTPase inhibition by CID-1067700.

However, caution is warranted with simvastatin as combination with chemotherapy may yield an antagonistic response. Further research is warranted to develop simvastatin as a potential drug candidate for the treatment of OCCC. 

Source: Oncotarget

Journal information: Arildsen N, Hedenfalk I. Simvastatin is a potential candidate drug in ovarian clear cell carcinomas. Oncotarget. 2020;11(40):3660-3674. doi:10.18632/oncotarget.27747