The aging brain and cognition: Contribution of vascular injury and Aβ to mild cognitive dysfunction

Natalie L. Marchant, Bruce R Reed, Nerses Sanossian, Cindee M. Madison, Stephen Kriger, Roxana Dhada, Wendy J. Mack, Charles DeCarli, Michael W. Weiner, Dan M Mungas, Helena C. Chui, William J. Jagust

Research output: Contribution to journalArticlepeer-review

86 Scopus citations


Importance: β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI's influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD). Objective: To examine the relationship between neuroimaging measures of VBI and brain Aβ deposition and their associations with cognition. Design and Setting: A cross-sectional study in a communityand clinic-based sample recruited for elevated vascular disease risk factors. Participants: Clinically normal (mean age, 77.1 years [N=30]), cognitively impaired (mean age, 78.0 years [N=24]), and mildly demented (mean age, 79.8 years [N=7]) participants. Interventions: Magnetic resonance imaging, Aβ (Pittsburgh Compound B-positron emission tomographic [PiBPET]) imaging, and cognitive testing. Main Outcome Measures: Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early Aβ deposition; PiB positivity (29 PiB positive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory. Results: Vascular brain injury and Aβ were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P<.05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI. Conclusions and Relevance: In this elderly sample with normal cognition to mild dementia, enriched for vascular disease, VBI was more influential than Aβ in contemporaneous cognitive function and remained predictive after including the possible influence of Aβ. There was no evidence that VBI increases the likelihood of Aβ deposition. This finding highlights the importance of VBI in mild cognitive impairment and suggests that the impact of cerebrovascular disease should be considered with respect to defining the etiology of mild cognitive impairment.

Original languageEnglish (US)
Pages (from-to)488-495
Number of pages8
JournalJAMA Neurology
Issue number4
StatePublished - Apr 2013

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Clinical Neurology


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