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Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition.

TitleAssociation Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition.
Publication TypeJournal Article
Year of Publication2017
AuthorsGottesman RF, Schneider ALC, Zhou Y, Coresh JJ, Green E, Gupta N, Knopman DS, Mintz A, Rahmim A, Sharrett ARichey, Wagenknecht LE, Wong DF
Secondary AuthorsMosley TH
JournalJAMA
Volume317
Issue14
Pagination1443-1450
Date Published2017 Apr 11
ISSN1538-3598
KeywordsAfrican Continental Ancestry Group, Age Factors, Aged, Aged, 80 and over, Alleles, Alzheimer Disease, Amyloid, Aniline Compounds, Apolipoproteins E, Body Mass Index, Brain, Dementia, Diabetes Complications, Ethylene Glycols, European Continental Ancestry Group, Female, Fluorine Radioisotopes, Follow-Up Studies, Humans, Hypercholesterolemia, Hypertension, Male, Middle Aged, Odds Ratio, Positron-Emission Tomography, Prospective Studies, Risk Factors, Smoking, Time Factors
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.

DOI10.1001/jama.2017.3090
Alternate JournalJAMA
PubMed ID28399252
PubMed Central IDPMC5921896
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
U01 HL096812 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
U01 HL096902 / HL / NHLBI NIH HHS / United States
R01 AG040282 / AG / NIA NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
U01 HL096814 / HL / NHLBI NIH HHS / United States
K24 AG052573 / AG / NIA NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
U01 HL096899 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States