Send to

Choose Destination
Hum Brain Mapp. 2016 Jul;37(7):2446-54. doi: 10.1002/hbm.23186. Epub 2016 Mar 23.

Small vessel disease and cognitive impairment: The relevance of central network connections.

Author information

Hemorrhagic Stroke Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Neurology, Cortical physiology laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Athinoula a. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, Massachusetts.
Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology & Neuroscience, King's College London, United Kingdom.


Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non-central brain network connections. Brain networks were reconstructed from diffusion-weighted MRI scans in 72 individuals (75 ± 8 years) with cognitive impairment and SVD on MRI. The centrality of white matter connections in the network was defined using graph theory. The association between the fractional anisotropy (FA) of central versus non-central connections, executive functioning, and markers of SVD was evaluated with linear regression and mediation analysis. Lower FA in central network connections was more strongly associated with impairment in executive functioning than FA in non-central network connections (r = 0.41 vs. r = 0.27; P < 0.05). Results were consistent across varying thresholds to define the central subnetwork (>50%-10% connections). Higher SVD burden was associated with lower FA in central as well as non-central network connections. However, only central network FA mediated the relationship between white matter hyperintensity volume and executive functioning [change in regression coefficient after mediation (95% CI): -0.15 (-0.35 to -0.02)]. The mediation effect was not observed for FA alterations in non-central network connections [-0.03 (-0.19 to 0.04)]. These findings suggest that the centrality of network connections, and thus their contribution to global network efficiency, appears to be relevant for understanding the relationship between SVD and cognitive impairment. Hum Brain Mapp 37:2446-2454, 2016.


cognition; diffusion tensor imaging; executive function; vascular brain injury; white matter

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center