Association between midlife vascular risk factors and estimated brain amyloid deposition

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

Prospective cohort study in 3 U.S. communities (Washington County, MD; Forsyth County, NC; and Jackson, MS). 346 participants without dementia in the Atherosclerosis Risk in Communities (ARIC)-PET Amyloid Imaging Study; evaluation of vascular risk factors and markers since 1987-1989, with florbetapir PET scans (2011-2013).

Exposures

Vascular risk factors at ARIC baseline (ages 45-64) were evaluated in multivariable models including age, sex, race, APOE genotype, and educational level.

Outcome

Standardized Uptake Value Ratios (SUVR) were calculated from PET scans; a mean global cortical SUVR was calculated. Elevated florbetapir (defined at SUVR>1.2) was the dependent variable.

Results

In 322 participants without dementia and with nonmissing midlife vascular risk factors at baseline (43% black, 58% female, mean age 52), SUVR (positive in 164 (50.9%) of participants) was measured >20 years later (median followup 23.5; IQR 23.0-24.3) when participants were 67-88 (mean 76 y). Elevated body mass index midlife (BMI) was associated with elevated SUVR (OR 2.06, 95% CI 1.16, 3.65). At baseline, 65 participants had no vascular risk factors, 123 had one, and 134 had two or more; a higher number of midlife risk factors was associated with elevated amyloid SUVR at followup, 30.8% (n=20), 50.4% (n=62), and 61.2% (n=82), respectively. In adjusted models, compared to 0 midlife vascular risk factors, the odds ratio for elevated SUVR associated with 1 vascular risk factor was 1.88 (95% CI 0.95-3.72) and was 2.88 (95% CI 1.46-5.69) for 2 or more vascular risk factors No significant race by risk factor interactions were found. Late-life vascular risk factors were not associated with late-life brain amyloid: (2 or more late-life vascular risk factors compared to 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’s Disease.