Simvastatin-Induced Cognitive Dysfunction: Two Case Reports

Chathurie Suraweera; Varuni de Silva; Raveen Hanwella


J Med Case Reports. 2016;10(83) 

In This Article


Simvastatin is a statin belonging to the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that lower cholesterol levels, particularly low-density lipoprotein (LDL) cholesterol and triglycerides. It increases high-density lipoprotein (HDL) cholesterol. Statins generally have minimal adverse effects, with the common side effects being myopathies, effects on liver enzymes, diarrhea, and, rarely, rhabdomyolysis.[1] Several case reports and case series have suggested a potential association between statins and cognitive impairment.[2]

With the increased diagnosis of hypercholesterolemia, the prescription of statins has also increased. Because cholesterol is heavily implicated as a causative factor in the formation of amyloid plaques, a reduction in cholesterol formation is postulated to slow plaque formation.[3] Statins are also reported to possess anti-inflammatory and anti-oxidant properties. There are several studies and meta-analyses[3] confirming the benefits of statin use on cognitive impairment.

Within the population receiving statins, there is a high proportion with memory loss and associated cognitive symptoms owing to the strong correlation of vascular risk factors, like diabetes and hypercholesterolemia, with vascular and Alzheimer's dementia. Statins are used to control vascular risk factors that may contribute to dementia, and there is emerging evidence that statins may play a protective role in improving memory problems in dementia.[4,5] However, there is also increasing concern that statins may be a causative factor for cognitive problems, mainly memory problems,[2] although this has not yet been reported as a side effect in the British National Formulary.

The postulation that statins can cause cognitive decline is based on the fact that lipophilic statins like atorvastatin and simvastatin show increased crossing of the blood–brain barrier compared to hydrophilic statins (for example, pravastatin and rosuvastatin). Two possible mechanisms are proposed: (1) the reduced availability of cholesterol caused by statins might impair the integrity of the neuronal and glial cell membrane, resulting in slowed conduction of neuronal impulses;[6] and (2) the reduced re-myelination and reduction in coenzyme Q10 levels impairs mitochondrial function and may lead to an increase in oxidative stress.[7,8] However, in a study investigating the long-term effects of treatment with pravastatin and atorvastatin in adult rats, pravastatin tended to impair learning, implying an impact on working memory and object recognition memory that was reversible on discontinuation, whereas atorvastatin did not impair either task. This model contradicts the postulated mechanism of lipophilic statins causing more cognitive impairment because pravastatin is hydrophilic and atorvastatin is lipophilic.[9] Two randomized control trials on simvastatin[10] and pravastatin,[11] which included a large number of patients, as well as a study conducted in Australia[12] did not identify a relationship between statin usage and cognitive decline. However, there are published case reports on statins causing memory loss.[13]

In a study of 60 patients who had memory loss associated with statins, 36 patients received simvastatin, 23 atorvastatin, and 1 pravastatin.[13] About 50 % of patients showed cognitive adverse effects within 2 months of therapy. A problem with this study, as well as most other case reports, is the lack of formal cognitive test results in the patients who developed cognitive changes. No specific memory test results were documented in any of the 60 reports. Four reports documented tests such as computed tomography, magnetic resonance imaging (MRI), intelligence quotient (IQ), and an unidentified cognitive test. Test results were normal for three of the four patients; MRI results were unknown for one patient.[13] In a randomized trial with healthy adults, simvastatin was associated with decreased performance on some neuropsychological tests compared with the placebo.[14] A survey conducted in 171 patients on statins reported that cognitive problems associated with statins have variable onset and recovery courses, and that there is a clear relationship with the potency, resulting in a significant negative impact on quality of life.[15] In 2012, the United States Food and Drug Administration (FDA) changed labeling for statins, advising of the possibility of cognitive impairment and further adding to the concerns regarding cognitive decline.[16]

We report the cases of two patients who reported memory loss and associated cognitive deficits after starting simvastatin and recovered following discontinuation. We did formal cognitive testing as well as brain imaging in both patients, which helps to rectify the lack of proper neuropsychiatric assessments in existing case studies.