Age and hippocampal volume predict distinct parts of default mode network activity

Group comparison studies have established that activity in the posterior part of the default-mode network (DMN) is down-regulated by both normal ageing and Alzheimer's disease (AD). In this study linear regression models were used to disentangle distinctive DMN activity patterns that are more profoundly associated with either normal ageing or a structural marker of neurodegeneration. 312 datasets inclusive of healthy adults and patients were analysed. Days of life at scan (DOL) and hippocampal volume were used as predictors. Group comparisons confirmed a significant association between functional connectivity in the posterior cingulate/retrosplenial cortex and precuneus and both ageing and AD. Fully-corrected regression models revealed that DOL significantly predicted DMN strength in these regions. No such effect, however, was predicted by hippocampal volume. A significant positive association was found between hippocampal volumes and DMN connectivity in the right temporo-parietal junction (TPJ). These results indicate that postero-medial DMN down-regulation may not be specific to neurodegenerative processes but may be more an indication of brain vulnerability to degeneration. The DMN-TPJ disconnection is instead linked to the volumetric properties of the hippocampus, may reflect early-stage regional accumulation of pathology and might be of aid in the clinical detection of abnormal ageing.