Cerebral Blood Flow Is Associated with Diagnostic Class and Cognitive Decline in Alzheimer’s Disease

Article type: Research Article

Authors: Duan, Wenna^a | Sehrawat, Parshant^a | Balachandrasekaran, Arvind^b | Bhumkar, Ashish B.^a | Boraste, Paresh B.^a | Becker, James T.^c | Kuller, Lewis H.^d | Lopez, Oscar L.^e | Gach, H. Michael^{f; *} | Dai, Weiying^{a; *}

Affiliations: [a] Department of Computer Science, State University of New York at Binghamton, Binghamton, NY, USA | [b] Harvard Medical School/Boston Children’s Hospital, Boston, MA, USA | [c] Departments of Psychiatry, Psychology, and Neurology, University of Pittsburgh, PA, USA | [d] Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA | [e] Departments of Neurology and Psychiatry, University of Pittsburgh, PA, USA | [f] Departments of Radiation Oncology, Radiology, and Biomedical Engineering, Washington University, Saint Louis, MO, USA

Correspondence: [*] Correspondence to: Weiying Dai, PhD, Binghamton University, 4400 Vestal Pkwy E, Binghamton, NY, 13902, USA. Tel.: +1 607 777 4859; E-mail: [email protected]. and H. Michael Gach, PhD, Washington University in St. Louis, 4921 Parkview Place, Saint Louis, MO 63110, USA. Tel.:+1 314 286 1645; E-mail: [email protected].

Abstract: Background:Reliable cerebral blood flow (CBF) biomarkers using a noninvasive imaging technique are sought to facilitate early diagnosis and intervention in early Alzheimer’s disease (AD). Objective:We aim to identify brain regions in which CBF values are affected and related to cognitive decline in early AD using a large cohort. Methods:Perfusion MRIs using continuous arterial spin labeling were acquired at 1.5 T in 58 normal controls (NC), 50 mild cognitive impairments (MCI), and 40 AD subjects from the Cardiovascular Health Study Cognition Study. Regional absolute CBF and normalized CBF (nCBF) values, without and with correction of partial volume effects, were compared across three groups. Association between regional CBF values and Modified Mini-Mental State Examination (3MSE) were investigated by multiple linear regression analyses adjusted for cardiovascular risk factors. Results:After correcting for partial volume effects and cardiovascular risk factors, ADs exhibited decreased nCBF with the strongest reduction in the bilateral posterior cingulate & precuneus region (p < 0.001) compared to NCs, and the strongest reduction in the bilateral superior medial frontal region (p < 0.001) compared to MCIs. MCIs exhibited the strongest nCBF decrease in the left hippocampus and nCBF increase in the right inferior frontal and insular region. The 3MSE scores within the symptomatic subjects were significantly associated with nCBF in the bilateral posterior and middle cingulate and parietal (p < 0.001), bilateral superior medial frontal (p < 0.001), bilateral temporoparietal (p < 0.02), and right hippocampus (p = 0.02) regions. Conclusion:Noninvasive perfusion MRI can detect functional changes across diagnostic class and serve as a staging biomarker of cognitive status.

Keywords: Alzheimer’s disease, arterial spin labeling, cerebral blood flow, cognition

DOI: 10.3233/JAD-200034

Journal: Journal of Alzheimer's Disease, vol. 76, no. 3, pp. 1103-1120, 2020