AbstractBackgroundMeaning in life (MiL) encompasses purpose in life (PiL), engagement with life (EwL), and sense of coherence (SoC) dimensions. MiL estimates have been associated with self‐reported cognitive status amongst middle‐aged individuals (Bartrés‐Faz et al., Alzheimers Res Ther. 2018;10(1):47). Later in life, MiL factors have been related to reduced cognitive decline and delayed onset of dementia in Alzheimer’s disease (AD; Boyle et al., Arch Gen Psychiatry. 2010;67(3):304‐310). However, how MiL dimensions are associated with brain networks’ expression and if these functional systems could mediate the influence of MiL on self‐perceived cognition remains unknown.MethodsDemographic, cognitive, and neuroimaging data was obtained from 585 middle‐aged adults (mean age 54.26 ± 7.1; 289 women) from the Barcelona Brain Health Initiative cohort (https://bbhi.cat/en/). Linear regression analyses were used to investigate the associations between MiL and its three dimensions [motivational (PiL), emotional (EwL), and cognitive (SoC)] and the strength of functional connectivity within the main brain resting‐state networks (RSNs; Shirer et al. Cereb Cortex. 2012;22(1):158‐165). Further analyses were computed to explore to which extent RSNs mediate the effect of MiL and its dimensions on self‐reported cognition, derived from the PROMIS® Cognitive Abilities and Concerns scale. Data was adjusted for age, personality, cognitive reserve, and affective status. Correction for multiple comparisons was applied.ResultsMiL estimates and its SoC factor, but not EwL and PiL, were correlated with RSNs. Specifically, significant associations for SoC emerged for those RSNs linked to higher‐order cognitive processing, such as the default‐mode, the salience and the left and right executive‐control networks. However, associations with sensorimotor systems were not significant. The links between SoC and self‐perceived cognitive function were mediated by the salience and the left executive‐control circuits (Fig. 1).ConclusionThe observed associations between SoC and the functional systems subtending cognitive processing, but not sensorimotor functions, may be related to previous observations indicating that MiL‐related factors are associated to greater than expected cognitive function for a given level of AD pathological load (Boyle et al., Arch Gen Psychiatry. 2012;69(5):499‐505), therefore promoting brain resilience in advanced age.