The Effects of Intracranial Stenosis on Cerebral Perfusion and Cognitive Performance

Article type: Research Article

Authors: Hilal, Saima^{a; b; c; *} | Mutsaerts, Henri J.M.M^{d; e} | Ferro, Doeschka A.^f | Petr, Jan^g | Kuijf, Hugo J.^h | Biessels, Geert Jan^f | Chen, Christopher^{a; b}

Affiliations: [a] Department of Pharmacology, National University of Singapore, Singapore | [b] Memory Aging and Cognition Center, National University Health System, Singapore | [c] Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore | [d] Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands | [e] Department of Radiology, Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands | [f] Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, the Netherlands | [g] Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, Dresden, Germany | [h] Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands

Correspondence: [*] Correspondence to: Saima Hilal, MD, PhD, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Level 4, Block MD3, 16 Medical Dr-ive, 117600, Singapore. Tel.: +65 65165885; E-mail: phchs@nus.edu.sg. Saw Swee Hock School of Public Health, MD 1, Tahir Foundation Building, 12 Science Drive 2, #10-03T, 117549, Singapore.

Abstract: Background:Intracranial stenosis (ICS) may contribute to cognitive dysfunction by decreased cerebral blood flow (CBF) which can be measured quantitatively by arterial spin labelling (ASL). Interpretation of CBF measurements with ASL, however, becomes difficult in patients with vascular disease due to prolonged arterial transit time (ATT). Recently, spatial coefficient of variation (sCoV) of ASL signal has been proposed that approximates ATT and utilized as a proxy marker for assessment of hemodynamic status of cerebral circulation. Objective:We investigate the association of ICS with CBF and sCoV parameters and its eventual effects on cognition in a memory clinic population. Methods:We included 381 patients (mean age = 72.3±7.9 years, women = 53.7%) who underwent 3T MRI and detailed neuropsychological assessment. ICS was defined as≥50% stenosis in any intracranial vessel on 3D Time-of-Flight MR Angiography. Gray matter sCoV and CBF were obtained from 2D EPI pseudo-continuous ASL images. Results:ICS was present in 58 (15.2%) patients. Patients with ICS had higher gray matter sCoV and lower CBF. The association with sCoV remained statistically significant after correction for cardiovascular risk factors. Moreover, ICS was associated with worse performance on visuoconstruction, which attenuated with higher sCoV. Mediation analysis showed that there was an indirect effect of ICS on visuoconstruction via sCoV. Conclusion:These findings suggest that compromised CBF as detected by higher sCoV is related to cognitive impairment among individuals diagnosed with ICS. We also showed that sCoV partially mediates the link between ICS and cognition. Therefore, sCoV may provide valuable hemodynamic information in patients with vascular disease.

Keywords: Arterial spin labeling, cerebral perfusion, coefficient of variation, cognition, intracranial stenosis

DOI: 10.3233/JAD-201131

Journal: Journal of Alzheimer's Disease, vol. 79, no. 3, pp. 1369-1380, 2021