Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition

JAMA. 2017 Apr 11;317(14):1443-1450. doi: 10.1001/jama.2017.3090.

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.

Publication types

  • Multicenter Study

MeSH terms

  • African Continental Ancestry Group
  • Age Factors*
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / genetics
  • Amyloid / metabolism*
  • Aniline Compounds / pharmacokinetics
  • Apolipoproteins E / genetics
  • Body Mass Index
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Dementia / etiology
  • Diabetes Complications
  • Ethylene Glycols / pharmacokinetics
  • European Continental Ancestry Group
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Follow-Up Studies
  • Humans
  • Hypercholesterolemia / complications
  • Hypertension / complications
  • Male
  • Middle Aged
  • Odds Ratio
  • Positron-Emission Tomography / methods
  • Prospective Studies
  • Risk Factors
  • Smoking / adverse effects
  • Time Factors

Substances

  • Amyloid
  • Aniline Compounds
  • Apolipoproteins E
  • Ethylene Glycols
  • Fluorine Radioisotopes
  • florbetapir