Science

Rebecca F. Gottesman, MD, PhD; Andrea L. C. Schneider, MD, PhD; Yun Zhou, PhD; Josef Coresh, MD, PhD; Edward Green, MD; Naresh Gupta, MD; David S. Knopman, MD; Akiva Mintz, MD; Arman Rahmim, PhD; A. Richey Sharrett, MD, DrPH; Lynne E. Wagenknecht, DrPH; Dean F. Wong, MD, PhD; Thomas H. Mosley, PhD

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 greater than or equal to 30, current smoking, hypertension, diabetes, and total cholesterol greater than or equal to 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 non missing 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 greater than or equal to 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.