STATINS, INCIDENT ALZHEIMER DISEASE, CHANGE IN COGNITIVE FUNCTION, AND NEUROPATHOLOGY

To the Editor:

Arvanitakis et al.¹ examined 929 cases from the Religious Orders Study to investigate whether statins modify the pathology associated with Alzheimer disease (AD). Large numbers of patients are necessary to determine the effects of medications on disease parameters. Typically, a small fraction of patients take the medication and only a fraction of those patients exhibit the specific phenotype of interest.

This study began with 929 patients of whom 119 were positive for statin use. The use of lipid-lowering medication is presumably by self-report, and there is no description of duration or dosing of medication. The authors used these cases to examine incident AD and then to examine effects on pathology. Only 199 or 231 out of the 989 cases had amyloid or tangle pathology, respectively; 16.6% of these cases used statins, which corresponds to 33 or 38 cases for amyloid or tangle pathology.

Presumably, only about one-third (10–12 cases) used a brain penetrant statin such as simvastatin. Obtaining statistical significance with such small numbers is difficult. Regardless of the considerations of number or power, we are struck by the absence of any effect associated with the statins. There was no overall effect for any measure. In addition, the authors stratified the results by type of medication: lipophilic statin, lipophobic statin, or nonstatin agent as well as by ApoE genotype. These stratifications could be important because other groups have observed more significant effects in ApoE4 subjects.^2,3

The absence of any effect is striking and contrasts with the Cache County cohort in which Li et al. observed that subjects taking statins showed a significant reduction in neurofibrillary plaque formation, but no change in neuritic plaque formation.⁴ Moreover, Arvanitakis et al. did not examine inflammatory markers, which are known to decrease in subjects taking statins.⁵

The discrepancy between the …