Lipophilic statins may raise risk of conversion from MCI to dementia

Reuters Health - 15/06/2021 - Among patients with early mild cognitive impairment (eMCI) and low to moderate serum cholesterol levels, those who take lipophilic statins have more than double the risk of converting to dementia over the next eight years, compared with statin non-use, a new study suggests.

In addition, PET scans of lipophilic-statin users showed a highly significant decline in metabolism in the posterior cingulate cortex, the brain region known to decline the most significantly in the earliest stages of Alzheimer's disease, the researchers found.

The study was reported at the Society of Nuclear Medicine and Molecular Imaging 2021 virtual annual meeting.

"Our research showed that therapy with statins - especially lipophilic statins - may have unintended negative consequences for brain health," Dr. Daniel H. Silverman of the University of California School of Medicine and UCLA Health System, in Los Angeles, told Reuters Health by email.

"For this reason, patients whose cholesterol levels are not markedly elevated (for example, under 200 mg/dL) and who have suffered some decline in their thinking abilities (such as memory or language facility) should work with their physicians to carefully consider alternatives before starting statin therapy," Dr. Silverman suggested.

"Alternatives could include more aggressive pursuit of lifestyle changes that have well-documented benefit to cardiovascular and cerebral function, such as a Mediterranean-type diet coupled with 150 minutes of moderate exercise per week," he added.

The literature on the effects of statins on cognition is mixed. Some studies have suggest that statins protect against dementia, while others assert that they accelerate the development of dementia.

To help clarify the relationship between statin use and long-term cognitive trajectory, the researchers analyzed eight years of data for 303 individuals with eMCI participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI).

They were grouped according to baseline cognitive status, baseline cholesterol levels and type of statin used. Participants underwent 18F-FDG PET imaging to identify any regions of declining cerebral metabolism within each statin group.

Over eight years, 24% of lipophilic-statin users converted to dementia compared with only 10% of non-statin users (P=0.04). The conversion rate of other statin users did not differ significantly from non-statin users (11%, P=0.94).

In addition, posterior cingulate metabolic decline was evident in lipophilic statin users, while no significant decline occurred among other statin users and non-users.

"In the short term, this research may provide additional motivation for people to seriously pursue paths such as eating right and exercising regularly before relying on statin therapy to reduce cholesterol level," Dr. Silverman told Reuters Health.

"In the longer term, it may serve to stimulate additional studies that contribute to a fuller understanding of neurotoxic exposures leading to or accelerating cognitive decline and dementia, which future research may then find ways to ameliorate," he said.

Dr. Silverman cautioned that the data are "observational rather than generated from a clinical trial in which subjects were randomized to be on one type of statin or another, or no statin at all - which would be the strongest type of experimental design from which to draw firm conclusions about clinical practice."

"While the data we are reporting may reasonably arouse caution in certain patients (for example, those with more cognitive symptoms and lower cholesterol levels) considering starting therapy with a lipophilic drug such as atorvastatin (Lipitor) or simvastatin (Zocor), ultimately they are limited to being able to raise this concern as a hypothesis, while a clear-cut test of this hypothesis would need to come from a randomized trial," he added.

SOURCE: https://bit.ly/3vrAiXL Society of Nuclear Medicine and Molecular Imaging 2021 annual meeting, held June 11-15, 2021.

By Megan Brooks



Posted on 15 June 202128 June 2021