Statin Therapy and Risk of Acute Memory Impairment
Authors: Brian L. Strom, Rita Schinnar, Jason Karlawish, Sean Hennessy, Valerie Teal, Warren B. Bilker
Journal: JAMA Internal Medicine (2015)

3][14] Mechanisms have been postulated both for impairment and improvement of memory with statin therapy.β-Amyloid plaques in the brain are thought to be related to dementia resulting from cholesterol buildup, 2,15-20 and the role of statins in interrupting deposition of plaques might delay the development of dementia. 2,21,22The lipophilicity of simvastatin and atorvastatin calcium that allows them to cross the blood-brain barrier could either confer protection 2,20 or adversely affect memory if statins interfere with myelin production in the brain. 2,23,24King et al 2 suggested that inhibition of myelin production could explain memory recovery after discontinuation of statin use because myelin stores can be replenished.6][27] The goal of our study was to investigate the association between use of statins and diagnosed acute memory impairment.Our hypothesis was that statin therapy would be associated with acute decline in the memory of patients receiving therapy compared with nonusers as well as users of other lipid-lowering drugs (LLDs). Methods Data SourceData were obtained from The Health Improvement Network (THIN), a database composed of the primary medical records from general practitioners (GPs) in the United Kingdom. 28HIN consists of the anonymized patient records that are extracted directly from GPs' offices.These data are collected IMPORTANCE Reports on the association between statins and memory impairment are inconsistent.OBJECTIVE To assess whether statin users show acute decline in memory compared with nonusers and with users of nonstatin lipid-lowering drugs (LLDs). DESIGN, SETTING, AND PARTICIPANTSUsing The Health Improvement Network database during January 13, 1987, through December 16, 2013, a retrospective cohort study compared 482 543 statin users with 2 control groups: 482 543 matched nonusers of any LLDs and all 26 484 users of nonstatin LLDs.A case-crossover study of 68 028 patients with incident acute memory loss evaluated exposure to statins during the period immediately before the outcome vs 3 earlier periods.Analysis was conducted from July 7, 2013, through January 15, 2015. RESULTSWhen compared with matched nonusers of any LLDs (using odds ratio [95% CI]), a strong association was present between first exposure to statins and incident acute memory loss diagnosed within 30 days immediately following exposure (fully adjusted, 4.40; 3.01-6.41).This association was not reproduced in the comparison of statins vs nonstatin LLDs (fully adjusted, 1.03; 0.63-1.66)but was also present when comparing nonstatin LLDs with matched nonuser controls (adjusted, 3.60; 1.34-9.70).The case-crossover analysis showed little association.CONCLUSIONS AND RELEVANCE Both statin and nonstatin LLDs were strongly associated with acute memory loss in the first 30 days following exposure in users compared with nonusers but not when compared with each other.Thus, either all LLDs cause acute memory loss regardless of drug class or the association is the result of detection bias rather than a causal association.