Abstract
Metabolic syndrome (MetS), the co-occurrence of obesity, hypertension, hyperglycemia and dyslipidema, is an important risk factor for diabetes, cardiovascular disease and end-organ damage in the brain. Our goal was to determine if metabolic syndrome (MetS) differentially affects cerebral metabolism in middle-aged adults with varying degrees of subclinical vascular disease. Sixty-five neurologically healthy adults aged 40 to 60 years (19 with MetS and 46 controls) underwent ultrasound examination of carotid artery intima-media thickness (IMT), a measure of peripheral vascular disease, a full neuropsychological evaluation, and a proton magnetic resonance spectroscopy ((1)H MRS) scan of occipitoparietal grey matter. The Johnson-Neyman technique and pick-a-point approach were used to test if MetS-related neurochemical changes were moderated by IMT. The MetS and control groups were comparable in age, education, gender distribution, average IMT, and cognitive performance. MetS individuals with low IMT values (1 SD below sample mean) demonstrated comparable neurochemical concentrations to the healthy controls (t = -0.21, p = 0.84, 95 % CI -0.106 to 0.086), while MetS individuals with high IMT values (1 SD above sample mean) exhibited significantly elevated glutamate concentrations (t = 2.84, p = 0.006, 95 % CI 0.038 to 0.220). We found that the level of peripheral atherosclerosis moderated the level of elevation of cerebral glutamate concentrations in patients with MetS. These results suggest that peripheral metabolic dysfunction in midlife likely acts in conjunction with subclinical vascular disease to foster pro-neurotoxic conditions in the central nervous system creating early brain vulnerability.