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

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.