Effects of intracranial stenosis on brain perfusion and cognitive performance in a memory clinic population

Background: Intracranial stenosis (ICS) contributes to cognitive dysfunction possibly via decreased cerebral blood flow (CBF). However, CBF measurements by Arterial Spin Labelling (ASL) are affected by vascular artefacts making it difficult to apply in elderly with large vessel disease. Recently, spatial coefficient of variance (CoV) is proposed as a robust estimate to quantify vascular artifacts and may be used as a proxy marker of large vessel insufficiency. We investigate the association of ICS with ASL measurements and its eventual effects on cognition in a memory clinic population.
Methods: We included 403 participants (mean age=72.3±7.9years, women=53.7%). ICS was graded as ≥50% stenosis in any intracranial vessel on 3D Time of Flight Magnetic Resonance Angiography. Gray matter spatial CoV and gray matter CBF were analyzed with ExploreASL from 2D EPI pseudo-continuous ASL images. Global cognition was assessed by a detailed neuropsychological test.
Results: ICS was present in 70 (17.4%) individuals. Persons with ICS had higher GM spatial CoV (mean difference (β)= 0.17, 95%CI: 0.07; 0.28, p=0.001) and lower CBF (β= -0.21, 95%CI: -0.33; -0.09), p=<0.001). This association persisted after partial volume correction of spatial CoV and CBF. The lateralization of spatial CoV and CBF (asymmetry index) (β for CoV: 0.23, 95%CI: 0.05; 0.40, p=0.013 and β for CBF: -0.22, 95%CI: -0.33; -0.11, p=<0.001) were correlated with ipsilateral stenosis. Spatial CoV was associated with worse cognition independent of CBF (β= -0.76, 95%CI: -1.09; -0.43, p=<0.001). Moreover, ICS was associated with global cognition, independent of gray matter CoV and CBF, although this effect attenuated in the presence of cortical microinfarcts (β= -0.23, 95%CI: -0.49; 0.02, p=0.072).
Conclusion: These findings suggest an association of ASL perfusion with ICS and cognition, which has a predominant component of large vessel insufficiency. Moreover, cortical microinfarcts mediate the link between ICS and cognition independent of large vessel insufficiency.