Response to Buslovich and Colleagues (2014)

We thank Buslovich and colleagues for their letter1 regarding our article on statins.2 Many of the questions that they raise refer to problems inherent to observational studies (vs randomized trials). Several trials of statins have been conducted that have considered cognition as a secondary endpoint but have had limitations, including restriction to individuals with cardiovascular disease, no separation between individuals with normal cognition and those with mild cognitive impairment at baseline, and lack of detailed longitudinal cognitive data. The current study took advantage of an observational data set with detailed longitudinal cognitive data and found protective effects of statins against cognitive decline for those with baseline normal cognition. As in any observational study, the findings could have resulted from uncontrolled confounding, but a number of possible confounders, including demographic characteristics, vascular comorbidities, and measured blood pressure were adjusted for. As Buslovich and colleagues noted, the comorbidity data were self-reported, a limitation. Lipid medication data were also self-reported, but restriction of the study to those who continuously or never took statins should have reduced misclassification, and reporting errors are less likely in individuals with normal cognition. Buslovich and colleagues also commented on several other things. The analyses were not conducted according to subtype of statins largely because there were insufficient numbers in different categories for analyses with good statistical power. Data on aspirin use were not included in analyses, because these were considered less accurate than data on prescription medications, and aspirin was not a priori considered to be a likely confounder. Other data, such as ratios of high-density lipoprotein cholesterol to low-density lipoprotein cholesterol, were not available. As shown in Table 1 and Figure 2, most people with normal cognition had a Clinical Dementia Rating sum of boxes score of 0 at baseline. Buslovich and colleagues comment that we did not know the reasons for loss to follow-up, a limitation. Indeed, given that the cohort was a dynamic one with new people entering over time, it is difficult to determine the difference between loss to follow-up and simply missing a visit. We agree with Buslovich and colleagues that the protective effects of statins were modest and that the population from Alzheimer's disease centers was a convenience sample, limiting the generalizability of the findings. We also agree that other important limitations were lack of data on lifetime statin use and short follow-up, but given the recent Food and Drug Administration decision calling attention to instances of memory loss in statin users, we believed it important to note that, in a large population of elderly adults with normal cognition, statin use was modestly protective against cognitive decline. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: All authors contributed to this paper. Sponsor's Role: None.