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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. [ABSTRACT FROM AUTHOR]

Metabolites produced by an altered gut microbiota might mediate the effects in the brain. Among metabolites, the fecal volatile organic compounds (VOCs) are considered to be potential biomarkers. In this study, we examined both the VOCs and bacterial taxa in the feces from healthy subjects and Alzheimer's disease (AD) patients at early and middle stages. Remarkably, 29 fecal VOCs and 13 bacterial genera were differentiated from the healthy subjects and the AD patients. In general, higher amounts of acids and esters were found in in the feces of the AD patients and terpenes, sulfur compounds and aldehydes in the healthy subjects. At the early stage of AD, the most relevant VOCs with a higher abundance were short-chain fatty acids and their producing bacteria, Faecalibacterium and Lachnoclostridium. Coinciding with the development of dementia in the AD patients, parallel rises of heptanoic acid and Peptococcus were observed. At a more advanced stage of AD, the microbiota and volatiles shifted towards a profile in the feces with increases in hexanoic acid, Ruminococcus and Blautia. The most remarkable VOCs that were associated with the healthy subjects were 4-ethyl-phenol and dodecanol, together with their possible producers Clostridium and Coprococcus. Our results revealed a VOCs and microbiota crosstalk in AD development and their profiles in the feces were specific depending on the stage of AD. Additionally, some of the most significant fecal VOCs identified in our study could be used as potential biomarkers for the initiation and progression of AD. [ABSTRACT FROM AUTHOR]