Early Amnestic Mild Cognitive Impairment Is Associated with Reduced Total Cerebral Blood Flow with no Brain Tissue Loss

Article type: Research Article

Authors: Liu, Che^{a; b; 1} | Lee, Sang H.^a | Loewenstein, David A.^c | Galvin, James E.^d | Levin, Bonnie E.^d | McKinney, Alexander^a | Alperin, Noam^{a; b; *; 1}

Affiliations: [a] Department of Radiology, University of Miami Miller School of Medicine, Miami, FL, USA | [b] Department of Biomedical Engineering, University of Miami, Miami, FL, USA | [c] Department of Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, USA | [d] Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

Correspondence: [*] Correspondence to: Noam Alperin, PhD, Department of Radiology, University of Miami Miller School of Medicine, PAC Building #713, 1150 NW 14th Street, Miami, FL33136, USA. Tel.: +1 305 243 8098; E-mail: nalperin@med.miami.edu.

Note: [1] These authors contributed equally to this work.

Abstract: Background:Lower cerebral blood flow (CBF) and excessive brain atrophy are linked to Alzheimer’s disease (AD). It is still undetermined whether reduced CBF precedes or follows brain tissue loss. Objective:We compared total CBF (tCBF), global cerebral perfusion (GCP), and volumes of AD-prone regions between cognitively normal (CN) and early amnestic mild cognitive impairment (aMCI) and tested their associations with cognitive performance to assess their predictive value for differentiation between CN and early aMCI. Methods:A total of 74 participants (mean age 69.9±6.2 years, 47 females) were classified into two groups: 50 CN and 24 aMCI, of whom 88% were early aMCI. tCBF, GCP, and global and regional brain volumetry were measured using phase-contrast and T1-weighted MRI. Neuropsychological tests tapping global cognition and four cognitive domains (memory, executive function, language, and visuospatial) were administered. Comparisons and associations were investigated using analyses of covariance (ANCOVA) and linear regression analyses, respectively. Results:Women had significantly higher GCP than men. Both, tCBF and GCP were significantly reduced in aMCI compared with CN, while differences in volumes of cerebral gray matter, white matter, and AD-prone regions were not significant. tCBF and GCP were significantly associated with global cognition (standardized beta (stβ) = 0.324 and stβ= 0.326) and with memory scores (stβ≥0.297 and stβ≥0.264) across all participants. Associations of tCBF and GCP with memory scores were also significant in CN (stβ= 0.327 and stβ= 0.284) and in aMCI (stβ= 0.627 and stβ= 0.485). Conclusion:Reduced tCBF and GCP are sensitive biomarkers of early aMCI that likely precede brain tissue loss.

Keywords: Amnestic mild cognitive impairment, cerebral blood flow, cerebral perfusion, global cognition, memory, phase-contrast MRI

DOI: 10.3233/JAD-220734

Journal: Journal of Alzheimer's Disease, vol. 91, no. 4, pp. 1313-1322, 2023