Statins, cognition, and dementia—systematic review and methodological commentary

Abstract

Firm conclusions about whether mid-life or long-term statin use has an impact on cognitive decline and dementia remain elusive. Here, our objective was to systematically review, synthesize and critique the epidemiological literature that examines the relationship between statin use and cognition, so as to assess the current state of knowledge, identify gaps in our understanding, and make recommendations for future research. We summarize the findings of randomized controlled trials (RCTs) and observational studies, grouped according to study design. We discuss the methods for each, and consider likely sources of bias, such as reverse causation and confounding. Although observational studies that considered statin use at or near the time of dementia diagnosis suggest a protective effect of statins, these findings could be attributable to reverse causation. RCTs and well-conducted observational studies of baseline statin use and subsequent cognition over several years of follow-up do not support a causal preventative effect of late-life statin use on cognitive decline or dementia. Given that much of the human research on statins and cognition in the future will be observational, careful study design and analysis will be essential.

Plasma sphingolipids and depressive symptoms in coronary artery disease

“…All participants were required to be taking a statin medication. This inclusion criterion was implemented in order to standardize the study population, as statins are the standard of care in CAD and may impact sphingolipid concentrations (Ng et al., 2014; Wei et al., 2013) as well as mood and cognition (Kim et al., 2015; Power, Weuve, Sharrett, Blacker, & Gottesman, 2015). …”

Impact of Baseline Features and Risk Factor Control on Cognitive Function in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial

“…In contrast, the association between good LDL control and cognitive impairment during follow-up in SAMMPRIS is more difficult to explain. While a few studies have suggested that lipid-lowering medication use may be linked to memory loss [23,24], an alternative explanation is that cholesterol levels decrease with age, chronic disease, poor nutrition, and inflammation, so perhaps the association between low LDL and cognitive impairment during follow-up is confounded by baseline older age or lower weight, which were associated with cognitive impairment in this study, or even related to another unmeasured factor. Another possibility for the paradoxical association between low LDL and cognitive impairment is that the result may be affected by index-event bias [25] because this analysis was focused on a different outcome (cognitive impairment) than the cohort was selected for in SAMMPRIS (stroke or TIA due to severe ICAS).…”

Statins and Brain Health: Alzheimer’s Disease and Cerebrovascular Disease Biomarkers in Older Adults

“…However, clinical studies of statins in aging and dementia have yielded only tenuous conclusions, with some observational data suggesting a protective association but other observational studies and randomized controlled trials not supporting this [6, 7]. In addition, existing studies using in vivo neuroimaging and postmortem neuropathology as outcomes have yielded conflicting results and have been limited by modest sample sizes and lack of generalizability [8–11].…”