TY - JOUR
T1 - Association between midlife vascular risk factors and estimated brain amyloid deposition
AU - Gottesman, Rebecca F.
AU - Schneider, Andrea L.C.
AU - Zhou, Yun
AU - Coresh, Josef
AU - Green, Edward
AU - Gupta, Naresh
AU - Knopman, David S.
AU - Mintz, Akiva
AU - Rahmim, Arman
AU - Sharrett, A. Richey
AU - Wagenknecht, Lynne E.
AU - Wong, Dean F.
AU - Mosley, Thomas H.
N1 - Publisher Copyright:
Copyright © 2017 American Medical Association. All rights reserved.
PY - 2017/4/11
Y1 - 2017/4/11
N2 - 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 -200mg/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.
AB - 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 -200mg/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.
UR - http://www.scopus.com/inward/record.url?scp=85017497741&partnerID=8YFLogxK
U2 - 10.1001/jama.2017.3090
DO - 10.1001/jama.2017.3090
M3 - Article
C2 - 28399252
AN - SCOPUS:85017497741
SN - 0098-7484
VL - 317
SP - 1443
EP - 1450
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 14
ER -