Abstract

Brain hypoperfusion is associated with cognitive impairment. Higher cerebrovascular impedance modulus (Z) may contribute to brain hypoperfusion. We tested hypotheses that patients with amnestic mild cognitive impairment (aMCI) (i.e., those who have a high risk of developing Alzheimer's disease) have higher Z than age-matched cognitively normal individuals, and that high Z is correlated with brain hypoperfusion. Fifty-eight patients with aMCI (67 ± 7 yr) and 25 cognitively normal subjects (CN, 65 ± 6 yr) underwent simultaneous measurements of carotid artery pressure (CAP, via applanation tonometry) and middle cerebral arterial blood velocity (CBV, via transcranial Doppler). Z was quantified using cross-spectral and transfer function analyses between dynamic changes in CBV and CAP. Patients with aMCI exhibited higher Z than NC (1.18 ± 0.34 vs. 1.01 ± 0.35 mmHg/cm/s, P = 0.044) in the frequency range from 0.78 to 4.29 Hz. The averaged Z in the frequency range (0.78-3.13 Hz) of high coherence (>0.9) was inversely correlated with total cerebral blood flow measured with 2-D Doppler ultrasonography normalized by the brain tissue mass (via structural MRI) across both patients with aMCI and NC (r = -0.311, P = 0.007), and in patients with aMCI alone (r = -0.306, P = 0.007). Our findings suggest that patients with aMCI have higher cerebrovascular impedance than cognitively normal older adults and that increased cerebrovascular impedance is associated with brain hypoperfusion.NEW & NOTEWORTHY This is the first study to compare cerebrovascular impedance between patients with amnestic mild cognitive impairment (aMCI) and age-matched cognitively normal individuals. Patients with aMCI had higher cerebrovascular impedance modulus than age-matched cognitively normal individuals, which was correlated with brain hypoperfusion. These results suggest the presence of cerebrovascular dysfunction in the dynamic regulation of cerebral blood flow in older adults who have high risks of Alzheimer's disease.

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