Association between midlife vascular risk factors and estimated brain amyloid deposition

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

Research output: Contribution to journalArticle

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 -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.

Original languageEnglish (US)
Pages (from-to)1443-1450
Number of pages8
JournalJAMA - Journal of the American Medical Association
Volume317
Issue number14
DOIs
StatePublished - Apr 11 2017

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Amyloid
Brain
Positron-Emission Tomography
Dementia
vascular factor
Odds Ratio
Atherosclerosis
Body Mass Index
Mississippi
Vascular Diseases

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Association between midlife vascular risk factors and estimated brain amyloid deposition. / Gottesman, Rebecca F; Schneider, Andrea L.C.; Zhou, Yun; Coresh, Josef; Green, Edward; Gupta, Naresh; Knopman, David S.; Mintz, Akiva; Rahmim, Arman; Sharrett, A. Richey; Wagenknecht, Lynne E.; Wong, Dean Foster; Mosley, Thomas H.

In: JAMA - Journal of the American Medical Association, Vol. 317, No. 14, 11.04.2017, p. 1443-1450.

Research output: Contribution to journalArticle

Gottesman, RF, Schneider, ALC, Zhou, Y, Coresh, J, Green, E, Gupta, N, Knopman, DS, Mintz, A, Rahmim, A, Sharrett, AR, Wagenknecht, LE, Wong, DF & Mosley, TH 2017, 'Association between midlife vascular risk factors and estimated brain amyloid deposition', JAMA - Journal of the American Medical Association, vol. 317, no. 14, pp. 1443-1450. https://doi.org/10.1001/jama.2017.3090
Gottesman, Rebecca F ; Schneider, Andrea L.C. ; Zhou, Yun ; Coresh, Josef ; Green, Edward ; Gupta, Naresh ; Knopman, David S. ; Mintz, Akiva ; Rahmim, Arman ; Sharrett, A. Richey ; Wagenknecht, Lynne E. ; Wong, Dean Foster ; Mosley, Thomas H. / Association between midlife vascular risk factors and estimated brain amyloid deposition. In: JAMA - Journal of the American Medical Association. 2017 ; Vol. 317, No. 14. pp. 1443-1450.
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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 Foster

AU - Mosley, Thomas H.

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.

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