Alzheimer’s Disease Biomarkers in Idiopathic Normal Pressure Hydrocephalus: Linking Functional Connectivity and Clinical Outcome

Article type: Research Article

Authors: Bommarito, Giulia^{a; *} | Van De Ville, Dimitri^{b; c} | Frisoni, Giovanni B.^d | Garibotto, Valentina^e | Ribaldi, Federica^d | Stampacchia, Sara^e | Assal, Frédéric^a | Allali, Gilles^{a; f} | Griffa, Alessandra^{a; b}

Affiliations: [a] Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland | [b] Institute of Bioengineering, Center of Neuroprosthetics, Ecole Polytechnique Fédérale De Lausanne (EPFL), Lausanne, Switzerland | [c] Department of Radiology and Medical Informatics, Geneva University Hospitals and University of Geneva, Geneva, Switzerland | [d] Memory Clinic, Department of Rehabilitation and Geriatrics, Geneva University and University Hospitals, Geneva, Switzerland | [e] Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospitals and NIMTlab, Geneva University, Geneva, Switzerland | [f] Department of Neurology, Division of Cognitive & Motor Aging, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY, USA

Correspondence: [*] Correspondence to: Giulia Bommarito, MD, PhD, Department of Clinical Neurosciences, Division of Neurology, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland. E-mail: giulia.bommarito@hcuge.ch, ORCID: https://orcid.org/0000-0003-2109-5443.

Abstract: Background:Alzheimer’s disease (AD) pathology impacts the response to treatment in patients with idiopathic normal pressure hydrocephalus (iNPH), possibly through changes in resting-state functional connectivity (rs-FC). Objective:To explore the relationship between cerebrospinal fluid biomarkers of AD and the default mode network (DMN)/hippocampal rs-FC in iNPH patients, based on their outcome after cerebrospinal fluid tap test (CSFTT), and in patients with AD. Methods:Twenty-six iNPH patients (mean age: 79.9±5.9 years; 12 females) underwent MRI and clinical assessment before and after CSFTT and were classified as responders (Resp) or not (NResp), based on the improvement at the timed up and go test and walking speed. Eleven AD patients (mean age: 70.91±5.2 years; 5 females), matched to iNPH for cognitive status, were also included. DMN and hippocampal rs-FC was related to amyloid-β42 and phosphorylated tau (pTau) levels. Results:Lower amyloid-β42 levels were associated with reduced inter- and intra-network rs-FC in NResp, and the interaction between amyloid-β42 and rs-FC was a predictor of outcome after CSFTT. The rs-FC between DMN and salience networks positively correlated to amyloid-β42 levels in both NResp and AD patients. The increase in the inter-network rs-FC after CSFTT was associated with higher pTau and lower amyloid-β42 levels in NResp, and to lower pTau levels in Resp. Conclusion:Amyloid-β42 and pTau impact on rs-FC and its changes after CSFTT in iNPH patients. The interaction between AD biomarkers and rs-FC might explain the responder status in iNPH.

Keywords: Alzheimer’s disease, amyloid, CSF tap test, default mode network, functional connectivity, hippocampus, normal pressure hydrocephalus, tau

DOI: 10.3233/JAD-210534

Journal: Journal of Alzheimer's Disease, vol. 83, no. 4, pp. 1717-1728, 2021