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

Matteo De Marco, Sebastien Ourselin, Annalena Venneri, Matteo De Marco, Sebastien Ourselin, Annalena Venneri

Abstract

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Results of the t test models testing the effect of ageing (healthy young > healthy old, cyan overlay) and the effect of AD (healthy old > AD dementia, green overlay) on the DMN. The same pattern emerged from the two models (x = −2; y = −44). z scores are indicated on the side of each output.
Figure 2
Figure 2
(a) The DMN map, as estimated with a one-sample t test carried out on the entire cohort and controlling for both proxies and all covariates (x = 6; z = 18; y = −62), and linear regression models testing the association between each of the proxies and functional connectivity of the DMN. Specifically, (b) the negative association between functional connectivity and the ageing proxy (x = −2; y = −44), and (c) the positive association between functional connectivity and the AD proxy (x = 6; x = 46). Uncorrected associations are shown in red, models corrected for the homologous proxy are shown in green, and the fully-corrected models are shown in cyan. z scores are indicated on the side of each output. (d) Association between functional connectivity of the DMN within the right TPJ (expressed as an average of z scores) and each of the two main independent variables of this study. (e) Association between the DMN signal in the right TPJ and performance on the Prose Memory test (delayed recall). Finally (f), the association between functional connectivity of each of the two proxies and the main DMN core. This core regions was located in the posterior cingulate cortex (BA 31, pFWE = 0.001, cluster extent: 12 contiguous voxels, peak Talairach coordinate: x = −4, y = −38, z = 26). The dotted lines represent linear associations. Pearson’s r coefficients and respective p values are shown. DMN: Default-Mode Network; TPJ: Temporo-Parietal Junction.

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