DISPROPORTIONATE INCREASE IN VENTRICULAR RELATIVE TO SULCAL CEREBROSPINAL FLUID VOLUME AND COGNITIVE FUNCTIONING: THE SMART-MR STUDY

Abstract

Global cerebral volume loss is associated with neurodegenerative diseases but also with normal aging. To understand their etiology studies aim to pinpoint specific brain tissue regions that are affected early in the disease process or investigate disproportionate volume loss of specific brain tissue regions. Here, we take a different perspective by examining the disproportionate increase in ventricular relative to sulcal cerebrospinal fluid (CSF) and the association with age and cognitive functioning. Within the SMART-MR study a 1.5T MRI was performed in 1232 patients with vascular disease (mean age 58±10 years, 80% male). Automated brain segmentation was used to quantify brain tissue volumes, CSF and lesions. The ventricular-sulcal CSF (VS) ratio was calculated by dividing ventricular volume by sulcal CSF volume. Z-scores for the domains memory and executive functioning were calculated. Multiple linear regression analysis was used to estimate the associations of VS ratio with age and with memory performance and executive functioning. The mean ventricular and sulcal CSF volumes were 31±15ml and 276±43ml, respectively. The VS ratio was 0.11±0.05. Pearson correlation coefficients between the natural log-transformed VS ratio and total brain volume, intracranial volume, brain parenchymal fraction, log-deep WMH, log-periventricular WMH, and age were 0.02 (p=0.52), 0.18, -0.40, 0.21, 0.33, and 0.35, respectively (p-values <0.0001). The VS ratio increased with older age (p<0.0001) independent of sex, total WMH, and ICV. It was also significantly associated with poorer memory performance (b of Z-score=-1.29; 95% CI -2.41 to -0.17) and poorer executive functioning (b of Z-score=-1.72; 95% CI -2.78 to -0.67), adjusted for age, sex, log-WMH, and ICV. In this population, a disproportionate increase in ventricular volume relative to sulcal CSF is associated with older age and with poorer memory and executive functioning. Future studies should investigate to what extent this is a biomarker of accelerated cognitive aging.