A new study challenges the myth that lowering cholesterol too much could increase the risk of dementia. Concerns arose after small, low-quality studies linked very low levels of low-density lipoprotein (LDL) cholesterol with higher rates of dementia. To address these concerns, researchers from Mass General Brigham examined data of 473 patients who had been diagnosed with atherosclerosis (hardened arteries due to plaque build-up) and had been followed for up to 7.2 years as a part of a randomized clinical trial program. The participants, who had an average age of 62 years, received two medications, a statin as well as evolocumab, to lower their LDL cholesterol. The researchers found no evidence of cognitive decline over the course of time the patients were followed. Results are published in NEJM Evidence.
Researchers assessed the study participants’ cognitive function annually, using standardized tests that assess short-term memory and use of strategy as well as reaction speed and executive function. There was no cognitive decline noted in the patients who received the LDL cholesterol-lowering medications. There was also no difference in cognitive function between those whose LDL levels were very low (below 25 mg/dl), compared with higher levels of LDL cholesterol. Finally, there was no cognitive function difference between patients who received placebo (in addition to a statin) in the randomized part of the study (over a median of 1.6 years) before switching to evolocumab plus a statin, and those who took evolocumab for a longer period.
The study was led by André Zimerman, MD, PhD, and Robert P. Giugliano, MD, SM, of the TIMI Study Group from the Division of Cardiovascular Medicine at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system.
“Unfounded fears that lowering LDL cholesterol too much is dangerous for the brain could lead some patients to forgo medications that prevent heart attacks, strokes, and peripheral artery disease,” said Giugliano. “While more research is ongoing, our study should be reassuring that lowering bad LDL cholesterol to very low levels does not appear to have any detrimental effects on the brain.” The authors note that these results support the findings of the American Heart Association’s 2022 Expert Scientific Statement on the safety of aggressive lowering of LDL cholesterol on brain function.
Authorship: In addition to Zimerman and Giugliano, Mass General Brigham authors include Michelle L. O’Donoghue, Xinhui Ran, Kyung Ah Im, and Marc S. Sabatine. Additional authors include Brian R. Ott, François Mach, Kenton Zavitz, Christopher E. Kurtz, Maria Laura Monsalvo, Bei Wang, Dan Atar, and Anthony Keech.
Disclosures: Disclosure forms can be found in the NEJM Evidence paper.
Funding: The EBBINGHAUS-OLE study was funded by Amgen.
Paper cited: Zimerman A et al. “Long-Term Cognitive Safety of Achieving Very Low LDL Cholesterol with Evolocumab” NEJM Evidence DOI: 10.1056/EVIDoa2400112
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