Revenge of the “sit” II: Does lifestyle impact neuronal and cognitive health through distinct mechanisms associated with sedentary behavior and physical activity?

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• There are positive benefits of physical activity (PA) on the brain and cognition.
• Sedentary behavior (SB) is known to negatively affect metabolic health.
• We review data relevant to how sedentary behavior may affect the brain.
• We review how PA and SB may interact in their effect on the brain and cognition.

It is generally understood that regular moderate to vigorous physical activity (MVPA) promotes good health from head to toe. Evidence also supports the notion that too much sitting can increase all-cause mortality and risk of chronic diseases such as diabetes. Moreover, there is evidence that daily MVPA may not offset negative effects of sedentary behavior on systemic risk factors. We extend the discussion to brain structure and function and argue that while MVPA is recognized as a protective behavior against age-related dementia, sedentary behavior may also be an important contributor to brain health and even counteract the benefits of MVPA due to overlapping or interacting mechanistic pathways. Thus, the goals of this review are (1) to outline evidence linking both PA and sedentary behavior to neurobiological systems that are known to influence behavioral outcomes such as cognitive aging and (2) to propose productive areas of future research.