Among the many factors examined in this review, only some are amenable to being evaluated in randomized controlled trials (RCTs), and only a subset of these have actually been studied in high-quality RCTs as potential interventions for preventing or delaying the onset of Alzheimer’s disease (AD) and cognitive decline. Effects of interventions in important subgroups, such as minority populations, were evaluated infrequently. A few of the factors considered in this report have shown potential promise in observational studies for both AD and cognitive decline, and in RCTs for at least one of the outcomes of interest. Moreover, several of the factors reviewed have demonstrated benefits beyond the potential of preserved cognition; that is, they promote overall health. Thus, there may be other reasons to recommend an intervention (e.g., increased physical activity) while further research is completed on its role in cognition.

The most general conclusions of this evidence report are summarized in Tables 74 and 75. These conclusions are based on a systematic review of the evidence for each factor, and on judgments about the quality of that evidence made using principles developed by the GRADE working group (www.gradeworkinggroup.org). For each factor examined, we considered the entire body of evidence and summarized the quality of that evidence as low, moderate, or high. The GRADE approach assigns an initial rating of “low” quality to observational studies and “high” quality to RCTs. These initial ratings may be modified by considerations relating to: detailed study design, consistency, strength of association, dose-response effect, directness, precision, and consideration of all plausible residual confounders that could reduce a demonstrated effect. Note that even within a given rating level, the quality of evidence may vary substantially; for example, there is considerable variability within the “low” quality level.

Table 74

Summary of findings on potential risk factors and interventions for AD.

Table 75

Summary of findings on potential risk factors and interventions for cognitive decline.

Tables 74 and 75 list, for AD and cognitive decline, respectively, the potential risk factors and interventions considered in this report, the associations observed between them and the outcome of interest (if any), and the quality of evidence supporting those associations. The tables also list factors for which the evidence was insufficient to establish whether or not an association exists. It is noteworthy that this last category includes many of the risk factors examined in this report.

In addition to sparse evidence, the extant research literature has other important limitations. Needed advances in study design and reporting include validated measures of exposure, pre-specified exposure categorizations, longer term trials, reporting of power calculations, and an agreed-upon battery of cognitive measures. Improving research design and reporting in these and other ways could improve confidence in observed associations and targeting of potential interventions. Conducting trials initially in those at high risk (e.g., those with mild cognitive impairment) would be an efficient approach. Well-designed, long-term cohort studies with robust measures of exposure and cognitive outcomes are needed to address the factors for which there is a strong biological mechanism or preliminary clinical evidence to suggest an important association.