Subclinical atherosclerosis is related to lower neuronal viability in middle-aged adults: A ¹H MRS study

Background: Increased carotid artery intima-media thickness (IMT) is a noninvasive marker of systemic arterial disease, associated with atherosclerosis, abnormal arterial mechanics, myocardial infarction, and stroke. In the elderly, clinically elevated IMT is related to diminished attention-executive function. In this context, previous work involving paper-and-pencil measures of cognition has demonstrated that a threshold of pathology (i.e., IMT ≥ 0.9 mm) is needed before IMT consistently relates to poor neuropsychological test performance. Given the critical role of arterial health in the development of cognitive dysfunction, the goal of this study was to investigate early markers of brain vulnerability by examining subclinical levels of IMT in relation to a sensitive marker of neuronal integrity, cerebral N-acetyl-aspartate/creatine (NAA/Cr) ratio, in midlife. Methods: A total of 40 participants aged 50 ± 6 years, underwent neuropsychological assessment, proton magnetic resonance spectroscopy (¹H MRS) examination of occipitoparietal grey matter and B-mode ultrasound of the common carotid artery. IMT was defined as the distance between the luminal-endothelial interface and the junction between the media and the adventitia. The relation between IMT and cerebral metabolite ratios was modeled using a single multivariate multiple regression analysis adjusted for age and current systolic blood pressure. Results: Increased IMT was associated with significantly lower NAA/Cr ratios (IMT beta = -0.62, p = 0.001), independent of age and systolic blood pressure (F(3,36) = 4.928, p = 0.006). Conclusions: Our study extends previous findings by demonstrating a significant relationship between IMT and NAA concentration, suggesting compromised neuronal viability even at IMT levels below thresholds for clinical end-organ damage.