Effects of Achieving an LDL-Cholesterol Level of <70 mg/dL Compared With the Goal of <100 mg/dL Using Simvastatin or Atorvastatin on Cognitive Processes in High-Risk Diabetic Patients

We aimed to compare the effects of an low-density lipoprotein (LDL)-cholesterol level of <70 mg/dL versus the goal of <100 mg/dL using simvastatin or atorvastatin on cognition. In this open-label trial, patients with diabetes were randomly assigned to simvastatin or atorvastatin 10 mg. If LDL-cholesterol levels, monitored at 30-day intervals, were ≥100 mg/dL, the doses of simvastatin and atorvastatin were increased to a maximum of 40 and 80 mg, respectively. Within each treatment group, patients were stratified by achieved LDL-cholesterol goals into 2 subgroups. Cognitive function was assessed using neuropsychological tests and event-related potential P300 at baseline and after 12 weeks. One hundred fourteen subjects completed the study. The mean LDL-cholesterol levels after simvastatin therapy was 60.2 mg/dL in the subgroup with LDL-cholesterol <70 mg/dL (n = 28) and 87.4 mg/dL in the subgroup with levels between 70 and 100 mg/dL (n = 29). After atorvastatin, mean LDL-cholesterol was 55.6 mg/dL in the subgroup with LDL-cholesterol <70 mg/dL (n = 30) compared with 86.8 mg/dL in the other subgroup (n = 27). In the simvastatin subgroup with LDL-cholesterol <70 mg/dL, significant performance decrements on neuropsychological tests of visuospatial perception, orientation, and minor improvement of immediate recall were noted. Executive functions, visuospatial organization worsened also with atorvastatin use. Minor improvement in short-term memory occurred in the atorvastatin subgroup with LDL-cholesterol levels of 70 to 100 mg/dL. No correlation existed between the changes in LDL-cholesterol levels and neuropsychological findings in all groups. This study provided partial support for decrements in cognitive functioning with simvastatin and atorvastatin regardless of achieved LDL-cholesterol goals. The clinical importance, however, is uncertain. However, a mild improvement in short-term memory after the use of both agents could not be excluded.