Background Studies have suggested associations between self-reported engagement in health behaviors and reduced risk of cognitive decline. Most studies explore these relationships using one health behavior, often cross-sectionally or with dementia as the outcome. In this study, we explored whether several individual self-reported health behaviors were associated with cognitive decline when considered simultaneously, using data from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), an Alzheimer’s disease risk-enriched cohort who were non-demented and in late midlife at baseline. Method We analyzed longitudinal cognitive data from 828 participants in WRAP, with a mean age at baseline cognitive assessment of 57 (range = 36-78, sd = 6.8) and an average of 6.3 years (standard deviation = 1.9, range = 2-10) of follow-up. The primary outcome was a multi-domain cognitive composite, and secondary outcomes were immediate/delayed memory and executive function composites. Predictors of interest were self-reported measures of physical activity, cognitive activity, adherence to a Mediterranean-style diet (MIND), and interactions with each other and age. We conducted linear mixed effects analyses within an Information-theoretic (IT) model averaging (MA) approach on a set of models including covariates and combinations of these 2- and 3-way interactions. The IT approach was selected due to the large number of interactions of interest and to avoid pitfalls of traditional model selection approaches. Results Model-averaged results identified no significant modifiable behavior*age interactions in relationship to the primary composite outcome. In secondary outcomes, higher MIND diet scores associated with slower decline in executive function. Men showed faster decline than women on delayed memory, independent of health behaviors. There were no other significant interactions among any other health behaviors and cognitive trajectories. Conclusions When multiple covariates and health behaviors were considered simultaneously, there were limited weak associations with cognitive decline in this age range. These results may be explained alone or in combination by three alternative explanations: 1) the range of cognitive decline is in middle age is too small to observe relationships with health behaviors, 2) the putative associations of these health behaviors on cognition may not be robust in this age range, or 3) the self-reported measures of the health behaviors may not be optimal for predicting cognitive decline. More study may be needed that incorporates sensitive measures of health behaviors, AD biomarker profiles, and/or other disease co-morbidities.