Clinically silent Alzheimer's and vascular pathologies influence brain networks supporting executive function in healthy older adults

Brian T. Gold, Christopher A. Brown, Jonathan G. Hakun, Leslie M. Shaw, John Q. Trojanowski, Charles D. Smith

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer's disease (AD) pathology and cerebral white-matter hyperintensities (WMHs). Twenty-nine younger adults and 34 cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging was performed. Older adults further underwent lumbar cerebrospinal fluid draw for the assessment of AD pathology and FLAIR imaging for the assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked with lower levels of clinically silent AD pathology. In addition, AD pathology and WMHs were each independently related to increased functional magnetic resonance imaging response in the left dorsolateral prefrontal cortex, a pattern associated with slower task performance. Our results suggest that clinically silent AD pathology is related to lower expression of a fronto-visual fC pattern supporting executive task performance. Further, our findings suggest that AD pathology and WMHs appear to be linked with ineffective increases in frontal response in CN older adults.

Original languageEnglish
Pages (from-to)102-111
Number of pages10
JournalNeurobiology of Aging
StatePublished - Oct 2017

Bibliographical note

Funding Information:
This study was supported by the National Institute on Aging (grant numbers RO1AG033036, P30AG028383, P01AG030128) and National Center for Advancing Translational Sciences of the National Institutes of Health (grant number TL1TR000115). In addition, John Q. Trojanowski is supported by P30AG10124 and U01AG24904, and Leslie M. Shaw is supported by U01AG24904. The authors thank Beverly Meacham for conducting some of the MRI scans and Dr Gregory Jicha for performing some of the lumbar CSF draws.

Publisher Copyright:
© 2017 Elsevier Inc.


  • Aging
  • Alzheimer's
  • Connectivity
  • Executive
  • Hyperintensities

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


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