Prospective memory performance and its resting-state functional connectivity correlates in individuals with memory complaints

This study aimed to investigate prospective memory (PM) in patients with memory complaints but without dementia (PWD) and correlate findings with resting-state functional connectivity (rsFC) alterations. We hypothesized that PM impairment would be evident at a certain relatively early point in the continuum and specific rsFC patterns would be the neuroimaging signature of this impairment. Sixty PWD participated in the study. The Memory Screening Test for Intentions and the Virtual Week were used to assess PM. Using the participants' PM scores as a regressor, the rsFC for PM was analyzed by Network-Based Statistics (NBS). Participants were divided into high and low PM groups (HPMG, LPMG) according to their PM scores and then their neuropsychological scores, rsFC patterns, and CSF biomarker levels were compared. The effect of education on the relationship between connectivity and CSF Aβ₄₂ level was examined by moderation analysis. Compared with HPMG, LPMG was impaired in both event- and time-based PM tasks, but the difference was more distinct in the event-based ones. While HPMG was more successful in event-based tasks than time-based ones, LPMG was not. As a result of NBS analysis, the middle frontal gyrus (MFG), supramarginal gyrus (SMG), and anterior cingulate cortex (ACC) were determined as central seeds. The HPMG's performance and connectivity were higher for most comparisons but had lower CSF Aβ₄₂ than LPMG and therefore was closer to the positivity threshold. When the education level was at the mean and above, there was a negative correlation between CSF Aβ₄₂ level and overall connectivity. The connectivities of MFG, SMG, and ACC play an important role in PM performance in the PWD. In more advanced PM impairment, the impairment of spontaneous processes is more prominent. At the onset of amyloidosis, the cognitive reserve may compensate for cognitive impairment by increasing connectivity.