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

TitleAssociation of Intracranial Atherosclerotic Disease With Brain β-Amyloid Deposition: Secondary Analysis of the ARIC Study.
Publication TypeJournal Article
Year of Publication2020
AuthorsGottesman RF, Mosley TH, Knopman DS, Hao Q, Wong D, Wagenknecht LE, Hughes TM, Qiao Y, Dearborn J
Secondary AuthorsWasserman BA
JournalJAMA Neurol
Date Published2020 Mar 01

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.

Alternate JournalJAMA Neurol
PubMed ID31860001
PubMed Central IDPMC6990749
Grant ListP30 AG049638 / AG / NIA NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
UL1 TR001863 / TR / NCATS NIH HHS / United States