Cardiovascular risk factors, cortisol, and amyloid-β deposition in Alzheimer's Disease Neuroimaging Initiative

Abstract

Background: There is epidemiological evidence that cardiovascular risk factors (CVRF) also are risk factors for Alzheimer's disease, but there is limited information on this from neuropathological studies, and even less from in vivo studies. Therefore, we examined the relationship between CVRF and amyloid-β (Aβ) brain burden measured by Pittsburgh Compound B-positron emission tomography (PiB-PET) studies in the Alzheimer's Disease Neuroimaging Initiative.

Methods: Ninety-nine subjects from the Alzheimer's Disease Neuroimaging Initiative cohort who had a PiB-PET study measure, apolipoprotein E genotyping data, and information available on CVRF (body mass index [BMI], systolic blood pressure, diastolic blood pressure [DBP], and cholesterol and fasting glucose test results) were included. Eighty-one subjects also had plasma cortisol, C-reactive protein, and superoxide dismutase 1 measurements. Stepwise regression models were used to assess the relation between the CVRF and the composite PiB-PET score.

Results: The first model included the following as baseline variables: age, clinical diagnosis, number of apolipoprotein ɛ4 alleles, BMI (P = .023), and DBP (P = .012). BMI showed an inverse relation with PiB-PET score, and DBP had a positive relation with PiB-PET score. In the second adjusted model, cortisol plasma levels were also associated with PiB-PET score (P = .004). Systolic blood pressure, cholesterol, or impaired fasting glucose were not found to be associated with PiB-PET values.

Conclusion: In this cross-sectional study, we found an association between Aβ brain burden measured in vivo and DBP and cortisol, indicating a possible link between these CVRF and Aβ burden measured by PiB-PET. These findings highlight the utility of biomarkers to explore potential pathways linking diverse Alzheimer's disease risk factors.

Fig. 1

Scatterplot with predicted robust regression slope for subjects with median age and vascular risk factor values, and representing subjects who are cog-nitively normal (CN) with no apolipoprotein E (APOE) ε4 alleles, mild cognitive impairment (MCI) subjects with one APOE ε4 allele, and Alzheimer’s disease (AD) subjects with one APOE ε4 allele. Values for CN subjects are represented with triangles, MCI subjects with crosses, and AD cases with squares. (A) Diastolic blood pressure and Pittsburgh Compound B (PiB)-positron emission tomography composite score. (B) Body mass index and PiB composite score.

Fig. 2

Scatterplot with predicted regression slopes for subjects with median age representing CN subjects with no APOE ε4 alleles. MCI subjects with one APOE ε4 allele, and AD subjects with one APOE ε4 allele. Values for CN subjects are represented with triangles, MCI subjects with crosses, and AD cases with squares.