Cerebrospinal Fluid Biomarkers to Differentiate Idiopathic Normal Pressure Hydrocephalus from Subcortical Ischemic Vascular Disease

Article type: Research Article

Authors: Manniche, Christina^{a; 1} | Simonsen, Anja Hviid^{a; 1; *} | Hasselbalch, Steen Gregers^a | Andreasson, Ulf^{b; c} | Zetterberg, Henrik^{b; c; d; e} | Blennow, Kaj^{b; c} | Høgh, Peter^f | Juhler, Marianne^g | Hejl, Anne-Mette^h

Affiliations: [a] Department of Neurology, Danish Dementia Research Centre, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark | [b] Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden | [c] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [d] UK Dementia Research Institute at UCL, London, UK | [e] Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK | [f] Department of Neurology, Regional Dementia Research Centre, Zealand University Hospital and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark | [g] Department of Neurosurgery, Copenhagen University Hospital, Copenhagen, Denmark | [h] Department of Neurology, Bispebjerg Hospital, Copenhagen, Denmark

Correspondence: [*] Correspondence to: Anja Hviid Simonsen, PhD, Danish Dementia Research Centre, Department of Neurology, Copenhagen University Hospital, Section 6991, Blegdamsvej 9, DK-2100, Copenhagen OE, Denmark. Tel.: +45 26 20 73 37; E-mail:anja.hviid.simonsen@regionh.dk.

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

Abstract: Background:Idiopathic normal pressure hydrocephalus (iNPH) remains a challenge to differentiate from subcortical ischemic vascular disease (SIVD). Despite major research efforts, the cerebrospinal fluid (CSF) biomarker profiles of the two diseases are still not known in detail. Objective:To determine if novel CSF biomarkers, neurofilament light (NFL) reflecting axonal damage, the synaptic protein neurogranin (NG), and the astroglial marker chitinase-3-like protein 1 (YKL-40), and the core Alzheimer’s disease (AD) biomarkers, amyloid-β 42 (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), can differentiate iNPH from SIVD. Patients with AD and healthy controls (HC) were included for comparison purposes. Methods:Patients with iNPH (n = 28), SIVD (n = 30), AD (n = 57), and HC (n = 33) were retrospectively included from the Danish Dementia Biobank. All patients with iNPH had effect of shunt surgery with a follow-up period of 4 to 69 months. CSF biomarkers were measured using immunoassays. Results:Lower levels of NFL, NG, Aβ42, and t-tau were found in patients with iNPH versus SIVD, while YKL-40 and p-tau were similar in the two diseases. NFL and Aβ42 were the most reliable biomarkers to differentiate iNPH from SIVD with an area under the curve (AUC) on 0.82 and 0.80, respectively. Combining NFL with Aβ42, t-tau, and p-tau resulted in an AUC of 0.90, which was equivalent to the diagnostic accuracy of all six biomarkers combined. Conclusion:An addition of NFL to the CSF panel of Aβ42, t-tau, and p-tau may improve the differentiation of iNPH from SIVD.

Keywords: Biomarkers, cerebrospinal fluid, normal pressure hydrocephalus, vascular dementia

DOI: 10.3233/JAD-200036

Journal: Journal of Alzheimer's Disease, vol. 75, no. 3, pp. 937-947, 2020