Working memory in healthy aging : The role of action mode network–frontoparietal network functional connectivity and TSPO-related neuroimmune variation

Sammanfattning

Cognitive aging is associated with substantial variability in working memory performance, yet the molecular and neural mechanisms underlying this variability remain incompletely understood. The present study examined whether translocator protein (TSPO) was associated with large-scale functional connectivity and working memory in healthy older adults. Thirty-nine adults aged 50–81 years underwent positron emission tomography with [¹¹C]PBR28 to assess TSPO binding, resting-state functional MRI to measure functional connectivity and behavioural assessment of working memory. The primary functional connectivity measure was coupling between the Action Mode Network (AMN) and Frontoparietal Network (FPN), two systems implicated in externally directed behaviour and executive control. Analyses were conducted using the CONN toolbox in MATLAB. Age was associated with AMN–FPN connectivity and with functional connectivity of both AMN and FPN; however, these effects did not survive correction after controlling for gray matter volume. TSPO binding was associated with functional network organisation in a network-specific manner. FPN TSPO was associated with AMN–FPN between-network connectivity, whereas AMN TSPO was associated with AMN functional connectivity; both associations remained significant after controlling for gray matter volume. Working memory was initially associated with AMN–FPN, AMN, and FPN connectivity; however, only the association with FPN connectivity remained significant after gray matter adjustment. These findings suggest that cognitive aging is associated with overlapping contributions from neuroimmune variation, structural integrity, and functional network organisation. In particular, TSPO-related variation may be relevant to functional network organisation beyond gray matter differences, whereas FPN connectivity may robustly relate to working memory in later adulthood.