Midlife Vascular Risk Factors and Brain Amyloid Deposition

Study Questions:

What is the association between midlife vascular risk factors and late-life brain amyloid deposition, measured using florbetapir positron emission tomography (PET)?


For this study, investigators used data from the ARIC (Atherosclerosis Risk in Communities)–PET Amyloid Imaging Study, a prospective cohort study among 346 participants without dementia in three US communities (Washington County, MD; Forsyth County, NC; and Jackson, MS) who have been evaluated for vascular risk factors and markers since 1987-1989 with florbetapir PET scans in 2011-2013. PET image analysis was completed in 2015. 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. 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.


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 >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% confidence interval [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 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).


The authors concluded that an increasing number of midlife vascular risk factors were significantly associated with elevated amyloid SUVR.


This study reports that a cumulative number of midlife vascular risk factors was associated with elevated brain amyloid and suggests that midlife, but not late-life, exposure to vascular risk factors is important for amyloid deposition. Overall, these findings tend to support a role of vascular disease in the development of Alzheimer disease. Future studies are indicated to assess whether modification of mid-life risk factors will reduce amyloid deposition and risk of Alzheimer disease.

Keywords: Alzheimer Disease, Amyloid, Body Mass Index, Cardiac Imaging Techniques, Cholesterol, Dementia, Diabetes Mellitus, Genotype, Geriatrics, Hypertension, Positron-Emission Tomography, Primary Prevention, Risk Factors, Smoking, Vascular Diseases

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