Convergent and Discriminant Validity of Default Mode Network and Limbic Network Perfusion in Amnestic Mild Cognitive Impairment Patients

Article type: Research Article

Authors: Quattrini, Giulia^{a; b} | Marizzoni, Moira^{a; c} | Pizzini, Francesca B.^d | Galazzo, Ilaria Boscolo^e | Aiello, Marco^f | Didic, Mira^{g; h} | Soricelli, Andrea^{f; i} | Albani, Diego^j | Romano, Melissa^a | Blin, Olivier^k | Forloni, Gianluigi^j | Golay, Xavier^l | Jovicich, Jorge^m | Nathan, Pradeep J.ⁿ | Richardson, Jill C.^o | Salvatore, Marco^f | Frisoni, Giovanni B.^p | Pievani, Michela^{a; *} | on behalf of the PharmaCog Consortium

Affiliations: [a] Laboratory of Alzheimer’s Neuroimaging and Epidemiology (LANE), IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [b] Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy | [c] Laboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy | [d] Radiology, Department of Diagnostic and Public Health, University of Verona, Verona, Italy | [e] Department of Computer Science, University of Verona, Verona, Italy | [f] IRCCS SDN, Napoli, Italy | [g] Aix-Marseille Univ, INSERM, INS, Instit Neurosci des Syst, Marseille, France | [h] APHM, Timone, Service de Neurologie et Neuropsychologie, Hôpital Timone Adultes, Marseille, France | [i] Department of Sport Sciences, University of Naples Parthenope, Naples, Italy | [j] Neuroscience Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milano, Italy | [k] Aix-Marseille Univ, INSERM, INS, Instit Neurosci des Syst, DHUNE, Ap-Hm, Marseille, France | [l] Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, London, United Kingdom | [m] Center for Mind/Brain Sciences - CIMeC, University of Trento, Rovereto, Italy | [n] Department of Psychiatry, University of Cambridge, Cambridge, UK | [o] Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, United Kingdom | [p] Memory Clinic and LANVIE-Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland

Correspondence: [*] Correspondence to: Michela Pievani, PhD, Laboratory Alzheimer’s Neuroimaging & Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, via Pilastroni 4, 25125 - Brescia, Italy. E-mail: [email protected].

Abstract: Background:Previous studies reported default mode network (DMN) and limbic network (LIN) brain perfusion deficits in patients with amnestic mild cognitive impairment (aMCI), frequently a prodromal stage of Alzheimer’s disease (AD). However, the validity of these measures as AD markers has not yet been tested using MRI arterial spin labeling (ASL). Objective:To investigate the convergent and discriminant validity of DMN and LIN perfusion in aMCI. Methods:We collected core AD markers (amyloid-β 42 [Aβ42], phosphorylated tau 181 levels in cerebrospinal fluid [CSF]), neurodegenerative (hippocampal volumes and CSF total tau), vascular (white matter hyperintensities), genetic (apolipoprotein E [APOE] status), and cognitive features (memory functioning on Paired Associate Learning test [PAL]) in 14 aMCI patients. Cerebral blood flow (CBF) was extracted from DMN and LIN using ASL and correlated with AD features to assess convergent validity. Discriminant validity was assessed carrying out the same analysis with AD-unrelated features, i.e., somatomotor and visual networks’ perfusion, cerebellar volume, and processing speed. Results:Perfusion was reduced in the DMN (F = 5.486, p = 0.039) and LIN (F = 12.678, p = 0.004) in APOE ɛ4 carriers compared to non-carriers. LIN perfusion correlated with CSF Aβ42 levels (r = 0.678, p = 0.022) and memory impairment (PAL, number of errors, r = –0.779, p = 0.002). No significant correlation was detected with tau, neurodegeneration, and vascular features, nor with AD-unrelated features. Conclusion:Our results support the validity of DMN and LIN ASL perfusion as AD markers in aMCI, indicating a significant correlation between CBF and amyloidosis, APOE ɛ4, and memory impairment.

Keywords: Alzheimer’s disease, arterial spin labeling, brain perfusion, default mode network, limbic network, mild cognitive impairment

DOI: 10.3233/JAD-210531

Journal: Journal of Alzheimer's Disease, vol. 82, no. 4, pp. 1797-1808, 2021