Structural and functional alterations of posterior cingulate cortex subregions in successful cognitive aging

Vollständiger Abstract

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Successful cognitive aging (SCA) describes the preservation of cognitive abilities into advanced age, but its neural basis remains incompletely understood. Metabolic and pathological evidence implicates the posterior cingulate cortex (PCC) as a key region supporting cognitive resilience. However, functionally distinct PCC subregions have rarely been examined using complementary structural, microstructural, and functional imaging measures. In this cross-sectional secondary analysis of publicly available Human Connectome Project in Aging data, we identified 29 adults aged at least 80 years who met successful cognitive aging criteria based on episodic memory and executive function. We selected 29 adults with normal aging (NA) group and 29 middle-aged adults (MA) group matched for sex and education, yielding 87 participants. We combined structural MRI, neurite orientation dispersion and density imaging, and resting-state functional MRI to assess multimodal features across three PCC subregions. These features included cortical thickness, Neurite Density Index (NDI), Orientation Dispersion Index (ODI), Free Water Fraction (FWF), and cortex-wide functional connectivity. Both older groups showed lower cortical thickness in the dorsal and ventral PCC than the MA group. Cortical thickness, NDI, and ODI did not differ significantly between successful and normal aging. FWF was numerically lower in the left ventral PCC in SCA group, but this exploratory observation did not reach significance (Tukey-adjusted P = 0.059). Compared with the NA group, the SCA group showed significantly weaker connectivity between all PCC subregions and widespread prefrontal cortices (adjusted P < 0.05). In the pooled older-adult sample, weaker left ventral PCC–medial prefrontal connectivity correlated with better episodic memory ( r = −0.430, FDR-adjusted P = 0.026), although neither within-group association was significant. These findings suggest that SCA was associated with lower PCC–prefrontal functional connectivity, but not with detectable preservation of PCC cortical thickness. The numerical FWF difference in the left ventral PCC remains exploratory and requires independent replication. These subregion-specific patterns provide a potential framework for understanding heterogeneous cognitive-aging trajectories, but require confirmation in larger longitudinal cohorts.