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AlzRisk Risk Factor Literature Search Strategy and Results

Risk Factor: Statin use
Risk Factor Type: Medications
Current Understanding:
The tables below summarize results from a series of observational studies of statin use in relation to AD dementia risk. Although there is significant heterogeneity of findings across studies, there is currently insufficient evidence to conclude that statin use affects risk of Alzheimer’s disease or all cause dementia. While research considering statin use at or within one year of the time of dementia consistently reports protective associations between statin use and Alzheimer’s disease, such studies are particularly susceptible to bias from and reverse causation (given that persons with cognitive deterioration may be less likely to be prescribed or continue taking a statin). Conversely, consistent with the results of randomized clinical trials, studies that tracked AD dementia risk over several years following assessment of statin use at a set “baseline” individually and collectively report no association. However, the relation between statin use and Alzheimer’s disease in the general population remains an open question. Most of these studies were conducted prior to the wide adoption of statin use for primary prevention. They are limited by small numbers of statin users and could not consider the impact of use of statins in midlife or sustained statin use from midlife to late life on dementia risk. Regardless, statins have demonstrated benefits on cardiovascular disease and mortality and are therefore are increasingly widely recommended for both primary and secondary prevention of cardiovascular events and associated mortality. For a more in-depth discussion of these studies considering the association between statin use and AD, please see the Discussion. An expanded examination of the relation between statins and dementia or cognitive decline can be found in the related published review, Power MC, Weuve J, Sharrett AR, Blacker D, Gottesman RF (Nature Reviews Neurology 2015, doi:10.1038/nrneurol.2015.35.
Last Search Completed: 20 March 2015 - Last content update released on 30 March 2015.

Risk Factor Overview

We conducted our systematic literature search in the Medline (via Pubmed) and Embase databases, limiting our articles to those added to the database on or before March 20, 2015. We used the Medline Medical Subject Headings (MeSH) database and the Embase EMTREE thesaurus, as well as relevant article abstracts and metadata, to compile lists of controlled vocabulary and free text terms that were incorporated into our search strategy. Our search terms included keywords for the exposure (e.g., “statins” or “atorvastatin”) the outcome (e.g., “Alzheimer”), and study design (e.g., “cohort” or “case-control”).

The search returned 366 citations from Medline/Pubmed and 839 from Embase; 228 duplicates were removed yielding 901 unique citations. We excluded 838 citations that did not meet our inclusion criteria (e.g., topic not appropriate, review or editorial, cross sectional or non-nested case-control study design), leaving 139 articles for full-text review. We then excluded 130 additional articles that did not meet the inclusion criteria, including three that published statins-Alzheimer’s disease results also published elsewhere in greater detail, leaving 9 eligible peer-reviewed publications.

Search Strategy Flowchart

Search Strategy

Using our systematic review methods, we developed a search strategy (tables below) for Pubmed and EMBASE.

Search Strategy Table