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Original Investigation
December 20, 2019

Association of Intracranial Atherosclerotic Disease With Brain β-Amyloid Deposition: Secondary Analysis of the ARIC Study

Author Affiliations
  • 1Department of Neurology, Johns Hopkins University, Baltimore, Maryland
  • 2Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland
  • 3Department of Medicine, University of Mississippi Medical Center, Jackson
  • 4Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 5Department of Neurology, Mount Sinai Medical Center, New York, New York
  • 6Department of Radiology, Johns Hopkins University, Baltimore, Maryland
  • 7Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 8Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 9Department of Neurology, Beth Israel Deaconness Medical Center, Harvard Medical School, Boston, Massachusetts
JAMA Neurol. 2020;77(3):350-357. doi:10.1001/jamaneurol.2019.4339
Key Points

Question  Is intracranial atherosclerotic disease (ICAD) cross-sectionally associated with brain β-amyloid in individuals without dementia from US communities?

Findings  In this cross-sectional study, 300 participants of the Atherosclerosis Risk in Communities positron emission tomography (PET) study completed florbetapir PET scans and magnetic resonance imaging high-resolution vessel wall imaging. In this sample, ICAD, including atherosclerotic plaque characteristics and measures of stenosis, was not associated with brain β-amyloid by PET.

Meaning  In individuals without dementia from US communities, neither ICAD features nor the degree of stenosis are associated with brain β-amyloid when studied cross-sectionally.

Abstract

Importance  Intracranial atherosclerotic disease (ICAD) is an important cause of stroke and has also been recently identified as an important risk factor for all-cause dementia, but the mechanism of its association with cognitive performance is not fully understood.

Objective  To test the hypothesis that ICAD is associated with cerebral β-amyloid deposition as a marker of Alzheimer disease.

Design, Setting, and Participants  This cross-sectional analysis of data collected from August 2011 through November 2014 was a community-based cohort study conducted in 3 US communities. Of 346 adults without dementia aged 70 to 90 years who were sequentially recruited from 3 of 4 sites of the larger Atherosclerosis Risk in Communities study into a study of brain florbetapir positron emission tomography (ARIC-PET), 300 met inclusion criteria. A total of 589 were approached about recruitment, of whom 346 (58.7%) consented (the remainder either met exclusion criteria for ARIC-PET or refused to participate). Data were analyzed from July 2017 through October 2019.

Exposures  Intracranial atherosclerotic disease presence, frequency, and extent of stenosis, by high-resolution vessel wall magnetic resonance imaging.

Main Outcomes and Measures  Global cortical standardized uptake value ratio (SUVR) of greater than 1.2 as measured by florbetapir PET. Models were conducted using logistic regression methods. In secondary analyses, we tested effect modifications by apolipoprotein E ε4 genotype with interaction terms and in stratified models and evaluated regional patterns of associations.

Results  In 300 participants (mean [SD] age, 76 [5] years; 132 African American individuals [44%], 167 women [56%], and 94 carriers of at least 1 apolipoprotein E ε4 allele [31%]), ICAD was found in 105 participants (35%) and mean (SD) SUVR was higher in individuals with vs without intracranial plaques (1.34 [0.29] vs 1.27 [0.23]; P = .03). In adjusted models, ICAD presence (plaque presence [adjusted odds ratio (aOR), 1.20; 95% CI, 0.69-2.07] and frequency [aOR, 1.10; 95% CI, 0.96-1.26]) was not associated significantly with elevated SUVR in the total sample. Furthermore, modest stenosis of the intracranial vessels (defined as >50% stenosis) was not associated with elevated SUVR (aOR, 2.33; 95% CI, 0.82-6.60).

Conclusions and Relevance  In this community-based cohort of adults without dementia, intracranial atherosclerotic plaque or stenosis was not associated with brain β-amyloid deposition.

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