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Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition.
JAMA 2017; 317(14):1443-1450JAMA

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.

Authors+Show Affiliations

Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland2Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.Department of Radiology, Section of High Resolution Brain PET Imaging, Johns Hopkins University School of Medicine, Baltimore, Maryland.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.Department of Radiology, University of Mississippi Medical Center, Jackson.Hagerstown Imaging, Hagerstown, Maryland.Department of Neurology, Mayo Clinic, Rochester, Minnesota.Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina.Department of Radiology, Section of High Resolution Brain PET Imaging, Johns Hopkins University School of Medicine, Baltimore, Maryland.Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina.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.Department of Medicine, University of Mississippi Medical Center, Jackson.

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

28399252

Citation

Gottesman, Rebecca F., et al. "Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition." JAMA, vol. 317, no. 14, 2017, pp. 1443-1450.
Gottesman RF, Schneider AL, Zhou Y, et al. Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition. JAMA. 2017;317(14):1443-1450.
Gottesman, R. F., Schneider, A. L., Zhou, Y., Coresh, J., Green, E., Gupta, N., ... Mosley, T. H. (2017). Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition. JAMA, 317(14), pp. 1443-1450. doi:10.1001/jama.2017.3090.
Gottesman RF, et al. Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition. JAMA. 2017 Apr 11;317(14):1443-1450. PubMed PMID: 28399252.
* Article titles in AMA citation format should be in sentence-case
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, PY - 2017/4/12/entrez PY - 2017/4/12/pubmed PY - 2017/6/6/medline SP - 1443 EP - 1450 JF - JAMA JO - JAMA VL - 317 IS - 14 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 ≥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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/28399252/Association_Between_Midlife_Vascular_Risk_Factors_and_Estimated_Brain_Amyloid_Deposition_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2017.3090 DB - PRIME DP - Unbound Medicine ER -