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. 2025 May 25.
doi: 10.1007/s11357-025-01701-x. Online ahead of print.

Cognitive and neuroimaging outcome of very prodromal dementia with Lewy bodies

Frédéric Blanc  1   2 , Vincent Bouteloup  3   4 , Claire Paquet  5 , Marie Chupin  6 , Florence Pasquier  7 , Audrey Gabelle  8 , Mathieu Ceccaldi  9 , Paulo Loureiro de Sousa  10 , Pierre Krolak-Salmon  11 , Renaud David  12 , Clara Fischer  6 , Jean-François Dartigues  3   13 , David Wallon  14 , Olivier Moreaud  15 , Mathilde Sauvée  15 , Catherine Belin  16 , Claire Roubaud  17 , Anne Botzung  18   10 , Alix Ravier  18 , Catherine Demuynck  18 , Izzie Namer  10 , Marie-Odile Habert  6 , Olivier Bousiges  18   10 , Benoît Schorr  18 , Candice Muller  18 , Nathalie Philippi  18   10 , Geneviève Chêne  3   4 , Benjamin Cretin  18   10 , Jean-François Mangin  6   19 , Carole Dufouil  3   4
Affiliations

Cognitive and neuroimaging outcome of very prodromal dementia with Lewy bodies

Frédéric Blanc et al. Geroscience. .

Abstract

The cognitive and neuroimaging evolution over the course of dementia with Lewy bodies (DLB) from prodromal stage - Pro-DLB (subjective (SCI) to mild cognitive impairment (MCI)) - is poorly understood. The aim of this study was to analyze from 5-year longitudinal data the trajectories of Pro-DLB patients. The "Lewy- MEMENTO" prospective clinical cohort recruited 773 patients for either SCI or MCI. The Pro-DLB group was compared to a group with prodromal Alzheimer's disease (Pro-AD), a group with "prodromal DLB and AD" (Pro-DLB + AD), and a group without prodromal DLB and AD (no symptom [NS]). We modeled the 5-year evolution of cognitive functions and the 2-year evolution of brain MRI volumetry on MRI and brain metabolism (FDG PET). The Pro-AD and Pro-DLB + AD groups had more cognitive and functional decline than the Pro-DLB and NS groups (P < .001). The Pro-DLB group had more cognitive decline than the NS group (P < .004). Incident dementia during the follow-up was higher in the Pro-AD (13.0 per 100 person-years) and Pro-DLB + AD (10.3) groups than in the Pro-DLB (1.02) and NS (0.44) groups (P < .001). The decline in the metabolism of the left orbitofrontal cortex was greater in the Pro-DLB + AD group. The volume decrease of hippocampi, entorhinal cortices, amygdalae, and left insula was higher in the Pro-AD and the pro-DLB + AD groups. Patients in the pro-DLB group had less cognitive, functional, brain volume, and metabolism decrease than patients in the Pro-AD and pro-DLB + AD groups. DLB would therefore be a less degenerative and more dysfunctional disease at the prodromal stage.

Keywords: Alzheimer’s disease; Dementia with Lewy bodies; Mild cognitive impairment; Prodromal; Subjective cognitive impairment.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was performed in accordance with the guidelines of the Declaration of Helsinki. Every participant provided written informed consent for the MEMENTO cohort, and the protocol was approved by the ethics committee (Comité de Protection des Personnes sud-ouest et outre-mer III, approval number 2010-A01394-35). The protocol is registered in ClinicalTrials.gov (Identifier: NCT01926249, https://clinicaltrials.gov/ct2/show/NCT01926249 ). Registration date: 16 August 2013. Consent for publication: Not applicable. Competing interests: F.B. was the national coordinator for France for the Eisai Delphia (E2027), Axovant Headway-DLB and therapeutic trials Roche Graduate therapeutic trial; he had received honoraria from Roche, Eisai and Biogen for oral presentations. The other authors declare that they have no competing interests or financial disclosure related to the present work.

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