Intracranial Arterial 4D Flow in Individuals with Mild Cognitive Impairment is Associated with Cognitive Performance and Amyloid Positivity

Article type: Research Article

Authors: Berman, Sara E.^{b; d; e} | Clark, Lindsay R.^{a; b; c} | Rivera-Rivera, Leonardo A.^f | Norton, Derek^k | Racine, Annie M.^b | Rowley, Howard A.^{b; g} | Bendlin, Barbara B.^{a; b; c} | Blennow, Kaj^{h; i} | Zetterberg, Henrik^{h; i; j; l} | Carlsson, Cynthia M.^{a; b; c} | Asthana, Sanjay^{a; b} | Turski, Patrick^{f; g} | Wieben, Oliver^{f; g} | Johnson, Sterling C.^{a; b; c; *}

Affiliations: [a] Geriatric Research Education and Clinical Center, William. S. Middleton Memorial Veterans Hospital, Madison, WI, USA | [b] Alzheimer’s Disease Research Center, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [c] Wisconsin Alzheimer’s Institute, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [d] Medical Scientist Training Program, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [e] Neuroscience Training Program, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [f] Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA | [g] Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [h] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden | [i] Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden | [j] Department of Molecular Neuroscience, University College London, Institute of Neurology, London, UK | [k] Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison WI, USA | [l] UK Dementia Research Institute, London, UK

Correspondence: [*] Correspondence to: Sterling C. Johnson, PhD, William S. Middleton Memorial VA Hospital, 2500 Overlook Terrace (11G), GRECC, Madison, WI 53705, USA. Tel.: +1 608 256 1901 x 11946; Fax: +1 608 280 7165; E-mail: [email protected].

Abstract: It is becoming increasingly recognized that cerebrovascular disease is a contributing factor in the pathogenesis of Alzheimer’s disease (AD). A unique 4D-Flow magnetic resonance imaging (MRI) technique, phase contrast vastly undersampled isotropic projection imaging (PC VIPR), enables examination of angiographic and quantitative metrics of blood flow in the arteries of the Circle of Willis within a single MRI acquisition. Thirty-eight participants with mild cognitive impairment (MCI) underwent a comprehensive neuroimaging protocol (including 4D-Flow imaging) and a standard neuropsychological battery. A subset of participants (n = 22) also underwent lumbar puncture and had cerebrospinal fluid (CSF) assayed for AD biomarkers. Cut-offs for biomarker positivity in CSF resulting from a receiver operating characteristic curve analysis of AD cases and controls from the larger Wisconsin Alzheimer’s Disease Research Center cohort were used to classify MCI participants as biomarker positive or negative on amyloid-β (Aβ42), total-tau and total-tau/Aβ42 ratio. Internal carotid artery (ICA) and middle cerebral artery (MCA) mean flow were associated with executive functioning performance, with lower mean flow corresponding to worse performance. MCI participants who were biomarker positive for Aβ42 had lower ICA mean flow than did those who were Aβ42 negative. In sum, mean ICA and MCA arterial flow was associated with cognitive performance in participants with MCI and lower flow in the ICA was associated with amyloid positivity. This provides further evidence for vascular health as a contributing factor in the etiopathogenesis of AD, and could represent a point to intervene in the disease process.

Keywords: Aging, Alzheimer’s disease, cerebrovascular disease, mild cognitive impairment

DOI: 10.3233/JAD-170402

Journal: Journal of Alzheimer's Disease, vol. 60, no. 1, pp. 243-252, 2017