Neural contributions to reduced fluid intelligence across the adult lifespan.

Fluid intelligence - the ability to solve novel, complex problems - declines steeply during healthy human aging. Using functional magnetic resonance imaging (fMRI), fluid intelligence has been repeatedly associated with activation of a frontoparietal brain network, and impairment following focal damage to these regions suggests that fluid intelligence depends on their integrity. It is therefore possible that age-related functional differences in frontoparietal activity contribute to the reduction in fluid intelligence. This paper reports on analysis of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data, a large, population-based cohort of healthy males and females across the adult lifespan. The data support a model in which age-related differences in fluid intelligence are partially mediated by the responsiveness of frontoparietal regions to novel problem-solving. We first replicate a prior finding of such mediation using an independent sample. We then precisely localise the mediating brain regions, and show that mediation is specifically associated with voxels most activated by cognitive demand, but not with voxels suppressed by cognitive demand. We quantify the robustness of this result to potential unmodelled confounders, and estimate the causal direction of the effects. Finally, exploratory analyses suggest that neural mediation of age-related differences in fluid intelligence is moderated by the variety of regular physical activities, more reliably than by their frequency or duration. An additional moderating role of the variety of non-physical activities emerged when controlling for head motion. A better understanding of the mechanisms that link healthy aging with lower fluid intelligence may suggest strategies for mitigating such decline. SIGNIFICANCE STATEMENT: Global populations are living longer, driving urgency to understand age-related cognitive declines. Fluid intelligence is of prime importance, because it reflects performance across many domains, and declines especially steeply during healthy aging. Despite consensus that fluid intelligence is associated with particular frontoparietal brain regions, little research has investigated suggestions that under-responsiveness of these regions mediates age-related decline. We replicate a recent demonstration of such mediation, showing specific association with brain regions most activated by cognitive demand, and robustness to moderate confounding by unmodelled variables. By showing that this mediation model is moderated by the variety of regular physical activities, more reliably than by their frequency or duration, we identify a potential modifiable lifestyle factor that may help promote successful aging.