Association of Cognitive Impairment in Patients on 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitors

Abstract

BackgroundAtherosclerotic cardiovascular diseases are the leading cause of death in the United States. A reduction in cholesterol with 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statin) significantly reduces mortality and morbidity. Statins may be associated with cognitive impairment or dementia. Our aim was to study the association of cognitive impairment or dementia in patients who were on a statin.MethodsElectronic medical records of 3,500 adult patients in our suburban internal medicine office were reviewed.ResultsThere were 720 (20.6%) patients in the statin treatment group. Dementia or cognitive impairment was an associated comorbid condition in 7.9% patients in the statin treatment group compared to 3.1% patients in the non-statin group (P < 0.001). Analysis of all of the patients with cognitive impairment or dementia showed that among the age ranges of 51 years through 100 years, the patients in the statin treatment group had a higher prevalence of cognitive impairment or dementia compared to the non-statin group. In the statin treatment group, we found significantly higher prevalence of hyperlipidemia (86.3%), hypertension (69.6%), diabetes mellitus (36.0%), osteoarthritis (31.5%), coronary artery disease (26.1%), hypothyroidism (21.5%) and depression (19.3%) compared to the non-statin group (P < 0.001). About 39.9% of the patients with dementia or cognitive impairment were on statin therapy compared to 18.9% patients who had no dementia or cognitive impairment and were on statin therapy (P < 0.001). Among the patients with cognitive deficit or dementia in the statin treatment group, the majority of the patients were either on atorvastatin (43.9%) or simvastatin (35.1%), followed by rosuvastatin (12.2%) and pravastatin (8.8%). We found greater odds of dementia or cognitive impairment with each year increase in age (1.3 times), in women (2.2 times), African American race (2.7 times), non-consumption of moderate amount of alcohol (two times), diabetes mellitus (1.6 times), hypothyroidism (1.7 times), cerebrovascular accident (3.2 times), and other rheumatological diseases (1.8 times).ConclusionsThe association of dementia or cognitive impairment was significantly higher in the patients who were on statin therapy compared to the patients who were not on a statin.

Cognitive Function Assessment in Patients on Moderate- or High-Intensity Statin Therapy

“…It appears to be the reason why atorvastatin and simvastatin have higher association with non-hepatocytic adverse effects, such as cognitive impairment, compared to all other lipophilic statins [51,54]. Our findings of higher association of cognitive impairment with lipophilic atorvastatin were aligned with the other studies that have demonstrated higher association and severity of cognitive impairment with lipophilic statins compared with hydrophilic statins [11,21,46,[59][60][61][62].…”

“…As early as in 1997, there have been implications of statin therapy with cognitive behavioral changes, such as increased violence [23]. Since then, there has been increasing data from case reports, various retrospective and prospective studies, which ultimately lead to the FDA formally recognizing that statins may cause cognitive impairment [7,9,11,19,23,46]. Muldoon et al have done multiple studies that tested attention, reaction time, and psychomotor speed of those on statins [7,9].…”

“…In 2014, the FDA released a report via the Adverse Event Reporting System (AERS) which reported that the patients experienced ill-defined memory loss, confusion, and foggy thinking after statin exposure [6,19]. A retrospective study of 3,500 patients found that patients on statin therapy had a significantly higher association of dementia or cognitive impairment compared to the patients who were not on statins (39.9% vs. 18.9%) [46]. A study by Wagstaff et al also observed cognitive impairment with statin therapy but could not determine the causal relationship [11].…”

“…We found that the cognitive impairment was most commonly associated with moderate-or high intensity atorvastatin therapy. A retrospective review of 3,500 patients revealed that among patients on statin treatment with cognitive deficit, the majority of the patients were on atorvastatin (43.9%) or simvastatin (35.1%) [46]. The study also found that cognitive impairment was significantly higher in the patients who were on lipophilic statins, such as atorvastatin and simvastatin, compared to the hydrophilic statins, such as rosuvastatin and pravastatin [46].…”

“…A retrospective review of 3,500 patients revealed that among patients on statin treatment with cognitive deficit, the majority of the patients were on atorvastatin (43.9%) or simvastatin (35.1%) [46]. The study also found that cognitive impairment was significantly higher in the patients who were on lipophilic statins, such as atorvastatin and simvastatin, compared to the hydrophilic statins, such as rosuvastatin and pravastatin [46]. The mechanism of such association has been proposed as the lipophilicity of the statin and its ability to cross the blood brain barrier.…”