Low cerebral blood flow is associated with lower memory function in metabolic syndrome

Abstract

Background: Metabolic syndrome (MetS)--a cluster of cardiovascular risk factors--is linked with cognitive decline and dementia. However, the brain changes underlying this link are presently unknown. In this study, we tested the relationship between MetS, cerebral blood flow (CBF), white matter hyperintensity burden, and gray matter (GM) volume in cognitively healthy late middle-aged adults. Additionally, the extent to which MetS was associated with cognitive performance was assessed.

Design and methods: Late middle-aged adults from the Wisconsin Registry for Alzheimer's Prevention (N = 69, mean age = 60.4 years) underwent a fasting blood draw, arterial spin labeling perfusion MRI, T1-weighted MRI, T2FLAIR MRI, and neuropsychological testing. MetS was defined as abnormalities on three or more factors, including abdominal obesity, triglycerides, HDL-cholesterol, blood pressure, and fasting glucose.

Results: Mean GM CBF was 15% lower in MetS compared to controls. Voxel-wise image analysis indicated that the MetS group had lower CBF across a large portion of the cortical surface, with the exception of medial and inferior parts of the occipital and temporal lobes. The MetS group also had lower immediate memory function; a mediation analysis indicated this relationship was partially mediated by CBF. Among the MetS factors, abdominal obesity and elevated triglycerides were most strongly associated with lower CBF.

Conclusions: The results underscore the importance of reducing the number of cardiovascular risk factors for maintaining CBF and cognition in an aging population.

Figure 1

Mean CBF is displayed by groups defined by the number of MetS factors present in an individual. CBF is adjusted by reference cluster and inversion time.

Figure 2

Participants with metabolic syndrome showed significantly lower CBF in large portions of the cortical surface of the frontal and parietal lobes, and the lateral and superior portions of the temporal and occipital lobes. Voxel-wise results are shown here at p < 0.05, FWE corrected, controlling for age, sex, and reference cluster. The color of the overlay reflects the size of the t-statistic.

Figure 3

The first model displays the total effect, c, between MetS and immediate memory. The second uses CBF as a mediator that is partially accounting for the effect between MetS and immediate memory. The indirect effect, ab = −0.41, is the portion of the effect accounted for by CBF. Significance of the mediation was determined using bootstrapping (k = 5000) with 95% confidence intervals of the indirect effect [−0.82, − 0.08]. Age, reference cluster, and inversion time were controlled.