Purpose in life may promote cognitive resilience through default‐mode network connectivity in middle‐aged adults

Abstract

AbstractBackgroundDisease‐modifying agents to counteract cognitive impairment in aging remain elusive, and identifying modifiable factors promoting brain reserve is paramount. In AD, education, occupation, and physical activity represent typical reserve proxies (Stern et al. Alzheimers Dement.2020;16(9):1305‐1311), but psychological factors are increasingly being recognized, as their operating biological mechanisms are elucidated (i.e., Arenaza‐Urquijo et al. Neurology 2020;95:e1571). Purpose in life (PiL), one of the pillars of psychological well‐being, was found to reduce the deleterious effects of AD‐related pathological changes on cognition (Boyle et al., Arch Gen Psychiatry. 2012;69(5):499‐505). However, whether PiL operates as a cognitive resilience factor in middle‐aged individuals, as well as its associated neural mechanisms remains unknown.MethodData was obtained from 573 middle‐aged adults (mean age 54.28±7.2; 275 women) from the Barcelona Brain Health Initiative cohort (Cattaneo et al. Front Aging Neurosci. 2018;10:321). Individuals with lower (LP; N = 131) and higher (HP; N = 94) PiL rates, according to the division of this variable into quintiles, were compared in terms of cognitive status; a measure reflecting brain burden (MRI‐derived white matter hyperintensities; WMHs); and resting‐state functional connectivity (rs‐FC), examining system segregation (SyS) using 14 brain circuits (Shirer et al. Cereb Cortex. 2012;22(1):158‐165).ResultsNeuropsychological status and WMHs burden did not differ between PiL groups. However, only in the LP group, greater WMHs entailed a negative impact on speed of processing and logical reasoning (Fig.1A‐B). Subjects in the HP group showed lower SyS on the dorsal DMN (dDMN), indicating lesser segregation of this network from other brain circuits (t = 2.423, p = 0.016; Fig.1C). Specifically, HP individuals had greater inter‐network connectivity between dDMN nodes and the rest of the brain. Conversely, subjects in the LP group exhibited more connectivity across DMN‐like regions. Notably, in the HP group, greater functional connectivity was positively correlated with cognitive function previously related to WMHs, while the opposite pattern was observed in the LP group (Fig.1D‐F).ConclusionExpanding previous findings on AD‐pathology and advanced age, present results suggest that higher rates of PiL may promote cognitive resilience already in middle age. Possible neurobiological mechanism by which PiL might operate could imply greater integration between the DMN and other brain areas.