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Original Investigation
April 11, 2017

Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition

Author Affiliations
  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 3Department of Radiology, Section of High Resolution Brain PET Imaging, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 4Department of Radiology, University of Mississippi Medical Center, Jackson
  • 5Hagerstown Imaging, Hagerstown, Maryland
  • 6Department of Neurology, Mayo Clinic, Rochester, Minnesota
  • 7Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 8Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
  • 9Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 10Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland
  • 11Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 12Department of Medicine, University of Mississippi Medical Center, Jackson
JAMA. 2017;317(14):1443-1450. doi:10.1001/jama.2017.3090
Key Points

Question  Are midlife vascular risk factors associated with late-life brain amyloid deposition?

Findings  In a prospective cohort study of 346 members of the community-based Atherosclerosis Risk in Communities (ARIC)–PET cohort without dementia, having 2 or more midlife vascular risk factors compared with none was significantly associated with elevated amyloid deposition in the brain (61.2% vs 30.8%). There was no significant association for late-life risk factors.

Meaning  These findings are consistent with a role of vascular disease in the development of Alzheimer disease.

Abstract

Importance  Midlife vascular risk factors have been associated with late-life dementia. Whether these risk factors directly contribute to brain amyloid deposition is less well understood.

Objective  To determine if midlife vascular risk factors are associated with late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET).

Design, Setting, and Participants  The Atherosclerosis Risk in Communities (ARIC)–PET Amyloid Imaging Study, a prospective cohort study among 346 participants without dementia in 3 US communities (Washington County, Maryland; Forsyth County, North Carolina; and Jackson, Mississippi) who have been evaluated for vascular risk factors and markers since 1987-1989 with florbetapir PET scans in 2011-2013. Positron emission tomography image analysis was completed in 2015.

Exposures  Vascular risk factors at ARIC baseline (age 45-64 years; risk factors included body mass index ≥30, current smoking, hypertension, diabetes, and total cholesterol ≥200 mg/dL) were evaluated in multivariable models including age, sex, race, APOE genotype, and educational level.

Main Outcomes and Measures  Standardized uptake value ratios (SUVRs) were calculated from PET scans and a mean global cortical SUVR was calculated. Elevated florbetapir (defined as a SUVR >1.2) was the dependent variable.

Results  Among 322 participants without dementia and with nonmissing midlife vascular risk factors at baseline (mean age, 52 years; 58% female; 43% black), the SUVR (elevated in 164 [50.9%] participants) was measured more than 20 years later (median follow-up, 23.5 years; interquartile range, 23.0-24.3 years) when participants were between 67 and 88 (mean, 76) years old. Elevated body mass index in midlife was associated with elevated SUVR (odds ratio [OR], 2.06; 95% CI, 1.16-3.65). At baseline, 65 participants had no vascular risk factors, 123 had 1, and 134 had 2 or more; a higher number of midlife risk factors was associated with elevated amyloid SUVR at follow-up (30.8% [n = 20], 50.4% [n = 62], and 61.2% [n = 82], respectively). In adjusted models, compared with 0 midlife vascular risk factors, the OR for elevated SUVR associated with 1 vascular risk factor was 1.88 (95% CI, 0.95-3.72) and for 2 or more vascular risk factors was 2.88 (95% CI, 1.46-5.69). No significant race × risk factor interactions were found. Late-life vascular risk factors were not associated with late-life brain amyloid deposition (for ≥2 late-life vascular risk factors vs 0: OR, 1.66; 95% CI, 0.75-3.69).

Conclusions and Relevance  An increasing number of midlife vascular risk factors was significantly associated with elevated amyloid SUVR; this association was not significant for late-life risk factors. These findings are consistent with a role of vascular disease in the development of Alzheimer disease.

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