Prodromal Alzheimer’s Disease: Global Cognition, Cue Efficiency, and Cerebrospinal Fluid Neurofilament Light Values Predict Short-Term Conversion to Dementia

Article type: Research Article

Authors: Méndez-Barrio, Carlota^a | Medina-Rodríguez, Manuel^{b; c} | Mendoza-Vázquez, Gonzalo^a | García-Roldán, Ernesto^{c; d} | Rodrigo-Herrero, Silvia^a | Luque-Tirado, Andrea^d | Almodóvar-Sierra, Ángela^d | Franco-Macías, Emilio^{c; d; *}

Affiliations: [a] Department of Neurology, Memory Unit, Juan Ramón Jiménez University Hospital, Huelva, Spain | [b] Department of Neurology, University Hospital Virgen del Rocío, Seville, Spain | [c] Biomedicine Institute of Seville IBiS, University Hospital Virgen del Rocio/CSIC/University of Seville, Seville, Spain | [d] Department of Neurology, Memory Unit, Virgen del Rocío University Hospital, Seville, Spain

Correspondence: [*] Correspondence to: Emilio Franco-Macías, PhD, Memory Unit, University Hospital Virgen del Rocío, Avda. Manuel Siurot s/n, Sevilla 41013, Spain. Tel.: +34 609732041; E-mail: [email protected].

Abstract: Background:Predicting which patients with prodromal AD (pAD) will imminently convert to dementia may be paramount in a memory clinical setting, especially with potential disease-modifying therapies on the horizon. Objective:To explore a practical tool for this prediction, combining cognitive tests and cerebrospinal fluid (CSF) biomarkers. Methods:We designed a longitudinal prospective, observational, and multicenter study, enrolling patients with pAD. Inclusion criteria comprised memory complaints, Mini-Mental State Examination (MMSE) score of≥22, memory impairment as indicated by the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT + IR) and/or TMA-93, Clinical Dementia Rating-Global Score (CDR-GS) of 0.5, and positive CSF Aβ42/Aβ40 ratio (<0.095, Euroimmun). The primary outcome was the conversion to dementia (CDR-GS≥1) within the first year of follow-up, referred to as “short-term conversion”. A multiple regression logistic model was adopted to design the “Predict Short-Term Conversion” (PSTC) score. Results:Between 2020 and 2022, 83 patients were recruited. The median age was 74, with 49.4% being women. Twenty-five (30.1%) patients were classified as short-term converters. The PSTC score incorporated baseline scores on MMSE ( ≤24 = 3, >24 = 0) and FCSRT + IR Total Recall ( ≤14 = 4, >14 = 0), and CSF neurofilament light chains (NfLs) concentrations (β=0.001299). The PSTC score demonstrated an area under the curve of 0.78 (95% CI: 0.67-0.90, p < 0.001), with a cutoff value of 5.14 presenting 76% sensitivity and 80% specificity. Conclusions:The PSTC score, comprising two relatively brief cognitive test scores and NfLs CSF concentrations, could be useful for predicting short-term converters among patients diagnosed with pAD.

Keywords: Alzheimer’s disease, conversion to dementia, Free and Cued Selective Reminding Test, global cognition, Mini-Mental State Examination, neurofilament light chains

DOI: 10.3233/JAD-240689

Journal: Journal of Alzheimer's Disease, vol. 101, no. 3, pp. 877-887, 2024