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Background and Purpose— This study aimed to monitor cognitive performance during a 3-year period in subjects with bilateral asymptomatic severe internal carotid artery stenosis and to explore the role of cerebral hemodynamics and atherosclerotic disease in the development of cognitive dysfunction. Methods— One hundred fifty-nine subjects with bilateral asymptomatic severe internal carotid artery stenosis were included and prospectively evaluated for a 3-year period. At entry, demographics, vascular risk profile, and pharmacological treatments were defined. Cognitive status was evaluated using the Mini-Mental State Examination at baseline and at follow-up. Cerebral hemodynamics was assessed by transcranial Doppler–based breath-holding index test. As a measure of the extent of systemic atherosclerotic disease, common carotid artery intima-media thickness was measured. A cutoff for pathological values was set at 0.69 for breath-holding index and 1.0 mm for intima-media thickness. Results— The risk of decreasing in Mini-Mental State Examination score increased progressively from patients with bilaterally normal to those with unilaterally abnormal breath-holding index, reaching the highest probability in patients with bilaterally abnormal breath-holding index ( P Conclusions— Our findings suggest that patients with asymptomatic bilateral severe internal carotid artery stenosis may be at risk of developing cognitive impairment. The evaluation of the hemodynamic status, besides providing insights about the possible mechanism behind the cognitive dysfunction present in carotid atherosclerotic disease, may be of help for the individuation of subjects deserving earlier and more aggressive treatments.