Elsevier

Neurobiology of Aging

Volume 54, June 2017, Pages 199-213
Neurobiology of Aging

Regular article
Sources of disconnection in neurocognitive aging: cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume

https://doi.org/10.1016/j.neurobiolaging.2017.01.027Get rights and content

Abstract

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the 3 imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function.

Section snippets

Participants

The participants were 145 healthy, community-dwelling adults (79 women) between 19 and 79 years of age recruited to be distributed relatively equally across 3 age categories: 19–39 years of age (n = 48), 40–59 years of age (n = 49), and 60–79 years of age (n = 48). Participants gave written informed consent for a protocol approved by the Duke University Institutional Review Board. All participants were right-handed by self-report, completed at least 12 years of education, were free from

Age correlations

The general summary measures for fluid cognition, white-matter integrity (FA), and resting-state connectivity exhibited significant age-related decline, whereas the general measure of WMH volume increased with age (Fig. 2). The age-related decline in general fluid cognition remained significant when partialled for the general measures of white-matter integrity, resting-state functional connectivity, and WMH volume, r = −0.517, p < 0.001. Similarly, the general imaging measures continued to

Discussion

These results illustrate the way in which models of age-related differences in brain imaging and cognitive measures vary with the level of analysis. At a general level of analysis, we defined fluid cognition by the first unrotated factor from 9 psychometric and RT tests, and in a similar manner defined each of 3 imaging modalities of white-matter integrity, resting-state connectivity, and WMH volume, from the first factor of several individual imaging measures. As we hypothesized, age exhibited

Conclusions

Models of neural disconnection in age-related cognitive decline vary across different levels of analysis. At a broad level, with a single measure of fluid cognition and summary measures of cerebral white-matter integrity, resting-state functional connectivity, and WMH volume, age had a strong and independent influence on the cognitive and imaging measures, and the imaging variables did not influence the age-cognition relation. At a more specific level of analysis, with individual measures of

Disclosure statement

The authors have no conflicts of interest to disclose.

Acknowledgements

This research was supported by NIH research grant R01 AG039684. The authors are grateful to Ling Zou, Syam Gadde, Chris Petty, Max Horowitz, and Kristin Sundy for their assistance.

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