Reciprocal Incremental Value of ¹⁸F-FDG-PET and Cerebrospinal Fluid Biomarkers in Mild Cognitive Impairment Patients Suspected for Alzheimer’s Disease and Inconclusive First Biomarker

Article type: Research Article

Authors: Massa, Federico^{a; 1; *} | Farotti, Lucia^{b; 1} | Eusebi, Paolo^{c; d} | Capello, Elisabetta^e | Dottorini, Massimo E.^f | Tranfaglia, Cristina^f | Bauckneht, Matteo^g | Morbelli, Silvia^{g; h} | Nobili, Flavio^{a; e} | Parnetti, Lucilla^b

Affiliations: [a] Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy | [b] Center for Memory Disorders and Laboratory of Clinical Neurochemistry, Neurology Clinic, University of Perugia, Perugia, Italy | [c] Section of Neurology, Department of Medicine, University of Perugia, Perugia, Italy | [d] Health Planning Service, Department of Epidemiology, Regional Health Authority of Umbria, Perugia, Italy | [e] Neurology Clinic, IRCCS Ospedale Policlinico San Martino, Genoa, Italy | [f] Nuclear Medicine Unit, “S. Maria della Misericordia” Hospital, Perugia, Italy | [g] Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy | [h] Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy

Correspondence: [*] Correspondence to: Federico Massa, MD, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy. E-mail: [email protected].

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

Abstract: Background:In Alzheimer’s disease (AD) diagnosis, both cerebrospinal fluid (CSF) biomarkers and FDG-PET sometimes give inconclusive results. Objective:To evaluate the incremental diagnostic value of FDG-PET over CSF biomarkers, and vice versa, in patients with mild cognitive impairment (MCI) and suspected AD, in which the first biomarker resulted inconclusive. Methods:A consecutive series of MCI patients was retrospectively selected from two Memory Clinics where, as per clinical routine, either the first biomarker choice is FDG-PET and CSF biomarkers are only used in patients with uninformative FDG-PET, or vice versa. We defined criteria of uncertainty in interpretation of FDG-PET and CSF biomarkers, according to current evidence. The final diagnosis was established according to clinical-neuropsychological follow-up of at least one year (mean 4.4±2.2). Results:When CSF was used as second biomarker after FDG-PET, 14 out of 36 (39%) received informative results. Among these 14 patients, 11 (79%) were correctly classified with respect to final diagnosis, thus with a relative incremental value of CSF over FDG-PET of 30.6%. When FDG-PET was used as second biomarker, 26 out of 39 (67%) received informative results. Among these 26 patients, 15 (58%) were correctly classified by FDG-PET with respect to final diagnosis, thus with a relative incremental value over CSF of 38.5%. Conclusion:Our real-world data confirm the added values of FDG-PET (or CSF) in a diagnostic pathway where CSF (or FDG-PET) was used as first biomarkers in suspected AD. These findings should be replicated in larger studies with prospective enrolment according to a Phase III design.

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarkers, FDG-PET, mild cognitive impairment

DOI: 10.3233/JAD-190539

Journal: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1193-1207, 2019