Does the use of some of the most commonly prescribed statins significantly increase the risk of developing dementia in patients with mild cognitive impairment?
Research presented at the Society of Nuclear Medicine and Molecular Imaging 2021 Annual Meeting advises that positron emission tomography (PET) scans of lipophilic statin users revealed a highly significant decline in metabolism in the area of the brain that is first impacted by Alzheimer's disease when those cholesterol-lowering drugs were used in certain circumstances.
In other words, according to the University of California at Los Angeles authors, taking lipophilic statins—which include atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin, and pitavastatin—appears to more than double those patients’ risk of developing dementia compared with those who do not take statins. While hydrophilic statins focus on the liver, lipophilic statins are distributed to tissues throughout the body.
“There have been many conflicting studies on the effects of statin drugs on cognition,” said Prasanna Padmanabham, project head of the statins and cognition in the molecular and medical pharmacology student research program at UCLA. “While some claim that statins protect users against dementia, others assert that they accelerate the development of dementia. Our study aimed to clarify the relationship between statin use and subject’s long-term cognitive trajectory.”
The study team looked at several factors:
• Neuropsychological status at baseline,
• Relatively high versus low serum cholesterol levels at baseline
• Statin use versus nonuse
• Among users, type of statin used.
“The present analysis focuses upon outcomes of subjects with early mild cognitive impairment (eMCI), comparing users of statins with known moderate (atorvastatin) or high (simvastatin) lipophilicity and blood-brain barrier penetrance (LS), to non-users (nonS), or users of other statins (OS),” the authors explain.
Participants were enrolled in the Alzheimer’s Disease Neuroimaging Initiative at over 50 North American sites. The patients were then grouped into those above (n = 103) or below (n = 200) the median cholesterol level of the nonuser subjects (206 mg/dl).
Researchers report that, while serum cholesterol levels at baseline ranged widely (101-358 mg/dl), among all eMCI subjects, the average baseline cholesterol levels did not significantly differ between those who converted to dementia within 96 months as opposed to those who did not.
After excluding statin users with less than 96 months of use, the below-median cholesterol group consisted of 157 patients—67 nonusers, 72 on lipophilic statins, and 18 on other statins; within that group, according to researchers, average serum levels also did not differ between those who did (166 mg/dl) and did not (171 mg/dl) convert to dementia.
“There was, however, a significant difference observed in conversion rates within this group according to statin use: among LS, 24% converted to dementia, vs. only 10% of nonS (P = .04) in the ensuing 96 months, while conversion rate of OS did not significantly differ from nonS subjects (11%, P = .94),” the authors point out. “Moreover, posterior cingulate metabolic decline was identified among LS users, (P <.0005, highly significant after statistical correction for multiple comparisons), while no significant decline occurred among OS and nonS subjects. Finally, in the above-median cholesterol stratum, the difference in conversion rates of statin users and nonusers was not significant (P = .72).”
That led to the conclusion that, among patients with early mild cognitive impairment and low-to-moderate serum cholesterol levels at baseline, patients prescribed lipophilic statins had more than twice the risk of developing dementia over 8 years of follow-up versus no statin use. Researchers emphasize that the patients also demonstrated a consequential decline in metabolism of the posterior cingulate cortex—the region of the brain most affected in the earliest stages of Alzheimer’s disease—even though no such decline was seen in users of other statins or those with higher baseline serum cholesterol levels.
“By characterizing the metabolic effects associated with statin use, we are providing a new application of PET to further our understanding of the relationship between one of the most commonly used classes of drugs and one of the most common afflictions of the aging brain,” Padmanabham said. “Findings from these scans could be used to inform patients’ decisions regarding which statin would be most optimal to use with respect to preservation of their cognition and ability to function independently.”
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