title: Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Gottesman
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Andrea L C
authors.initials: AL
authors.lastname: Schneider
authors.affiliation: Department of Radiology, Section of High Resolution Brain PET Imaging, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.affiliation: Department of Radiology, University of Mississippi Medical Center, Jackson.
authors.forename: Edward
authors.initials: E
authors.lastname: Green
authors.affiliation: Hagerstown Imaging, Hagerstown, Maryland.
authors.forename: Naresh
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Akiva
authors.initials: A
authors.lastname: Mintz
authors.affiliation: Department of Radiology, Section of High Resolution Brain PET Imaging, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Arman
authors.initials: A
authors.lastname: Rahmim
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.affiliation: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.affiliation: Department of Radiology, Section of High Resolution Brain PET Imaging, Johns Hopkins University School of Medicine, Baltimore, Maryland9Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland10Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland11Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds / Q000493:pharmacokinetics; D001057:Apolipoproteins E / Q000235:genetics; D044383:Black People; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003704:Dementia / Q000209:etiology; D048909:Diabetes Complications; D005026:Ethylene Glycols / Q000493:pharmacokinetics; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D006973:Hypertension / Q000150:complications; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D049268:Positron-Emission Tomography / Q000379:methods; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors; D044465:White People
chemical_list: D000682:Amyloid; D000814:Aniline Compounds; D001057:Apolipoproteins E; D005026:Ethylene Glycols; D005462:Fluorine Radioisotopes; C545186:florbetapir