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Healthy aging is typically accompanied by cognitive decline. Previous work has shown that engaging in multiple, non-work activities during midlife can have a protective effect on cognition several decades later, rendering it less dependent on brain structural health; the definition of "cognitive reserve". Other work has shown that increasing age is associated with reduced segregation of large-scale brain functional networks. Here we tested the hypothesis that functional segregation (SyS) mediates this effect of middle-aged lifestyle on late-life cognition. We used fMRI data from three tasks in the CamCAN dataset, together with cognitive data on fluid intelligence, episodic memory, and retrospective lifestyle data from the Lifetime of Experiences Questionnaire (LEQ). In all three tasks, we showed that SyS related to fluid intelligence even after adjusting for the (nonlinear) age effects. However, we found no evidence that SyS in late-life mediated the relationship between non-specific (non-occupation) midlife activities and either measure of cognition in late-life. Thus, the brain correlates of cognitive reserve arising from mid-life activities remain to be discovered. • System segregation (SyS) is stable across different brain states. • SyS is negatively associated with age. • Fluid intelligence, but not episodic memory, was robustly predicted by SyS. • Late life SyS was not associated with midlife outside of work activities. [ABSTRACT FROM AUTHOR]

Abstract: Older adults often exhibit elevated false recognition for events that never occurred, while simultaneously experiencing difficulty in recognizing events that actually occurred. It has been proposed that reduced recollection in conjunction with an over-reliance on familiarity may contribute to this pattern of results. This explanation is somewhat inconsistent, however, with recent evidence suggesting that familiarity and associated neural activity are reduced in healthy aging. Alternatively, given that illusory memory may be based, in part, on veridical memory processes (recollection/familiarity), one might predict that older adults exhibit enhanced false alarm rates because the neural signatures associated with true recognition (hits) and false recognition (false alarms) are less distinguishable in old than in young adults. Here, we used event-related fMRI to measure the effects of aging on neural activity associated with recollection, familiarity and familiarity-based false alarms for objects in young and older adults. Compared to young adults, older adults exhibited elevated false alarm rates and impaired behavioral indices of recollection and familiarity. Imaging data showed that older adults exhibited reduced recollection effects in the left parietoccipital cortex. Furthermore, while similar regions in frontal, parietal, lateral and inferior temporal cortices contributed to familiarity-based true and false recognition, reduced familiarity-related activity in frontal and inferior temporal regions in the older adults resulted in decreased differentiation between true and false recognition effects in this group. Our results suggest that reductions in neural activity associated with both recollection and familiarity for studied items may contribute to elevated false recognition in older adults, via reduced differentiation between the neural activity associated with true and false memory. [ABSTRACT FROM AUTHOR]