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: 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.

Figure 1

Adjusted odds ratios for elevated florbetapir by number of vascular risk factors, midlife through late-life. Adjusted ORs and 95% CI are displayed for number of vascular risk factors for each visit, 1 through 5, for elevated SUVR (>1.2). Models adjusted for age (at visit 5, 2011-2013), sex, race, education level, APOE ε4 genotype. Vascular risk factors included: body mass index ≥30 kg/m2, current smoking, hypertension, diabetes, and total cholesterol ≥200 mg/dl.

Figure 2

LOWESS curves demonstrating associations between midlife vascular risk factors and florbetapir by APOE status. Curves show smoothed associations between vascular risk factors in midlife (visit 1, 1987-1989) and continuous global cortex Florbetapir SUVR, by APOE status (0 APOE ε4 alleles [n=222] versus 1 or 2 APOE ε4 alleles [n=100]).

Figure 2

LOWESS curves demonstrating associations between midlife vascular risk factors and florbetapir by APOE status. Curves show smoothed associations between vascular risk factors in midlife (visit 1, 1987-1989) and continuous global cortex Florbetapir SUVR, by APOE status (0 APOE ε4 alleles [n=222] versus 1 or 2 APOE ε4 alleles [n=100]).

Figure 2

LOWESS curves demonstrating associations between midlife vascular risk factors and florbetapir by APOE status. Curves show smoothed associations between vascular risk factors in midlife (visit 1, 1987-1989) and continuous global cortex Florbetapir SUVR, by APOE status (0 APOE ε4 alleles [n=222] versus 1 or 2 APOE ε4 alleles [n=100]).