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. 2025 Jun 24;17(2):e70141.
doi: 10.1002/dad2.70141. eCollection 2025 Apr-Jun.

Faster decline of very prodromal dementia with Lewy bodies when amyloid positive

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  2 , Pierre Krolak-Salmon  10 , Renaud David  11 , Clara Fischer  6 , Jean-François Dartigues  3   12 , David Wallon  13 , Olivier Moreaud  14 , Mathilde Sauvée  14 , Catherine Belin  15 , Claire Roubaud Baudron  16 , Anne Botzung  1   2 , Alix Ravier  1 , Catherine Demuynck  1 , Izzie Namer  2 , Marie-Odile Habert  6 , Olivier Bousiges  1   2 , Benoît Schorr  1 , Candice Muller  1 , Nathalie Philippi  1   2 , Geneviève Chêne  3   4 , Benjamin Cretin  1   2 , Jean-François Mangin  6   17 , Carole Dufouil  3   4
Affiliations

Faster decline of very prodromal dementia with Lewy bodies when amyloid positive

Frédéric Blanc et al. Alzheimers Dement (Amst). .

Abstract

Introduction: The cognitive and neuroimaging evolution during dementia with Lewy bodies (DLB) from the prodromal phase (Pro-DLB; subjective cognitive impairment [SCI] to mild cognitive impairment [MCI]) according to amyloid beta (Aβ) status is poorly understood.

Methods: The decline of Lewy-Memento patients with SCI or MCI was compared according to Aβ status across four groups: Pro-DLB, prodromal Alzheimer's disease (Pro-AD), Pro-DLB+AD, and a group without prodromal DLB and AD (no symptoms [NS]). We observed the evolution of cognitive, functional, quality of life measures, brain volumetry, and metabolism on fluorodeoxyglucose positron emission tomography.

Results: In the Pro-DLB and Pro-DLB+AD groups, Aβ+ patients had more cognitive and functional decline than the Aβ- patients. In the Pro-AD and NS groups, Aβ+ patients had more functional decline. Aβ+ Pro-AD showed a greater volume decline of the brain (left insula).

Discussion: The presence of amyloid lesions worsens very prodromal DLB patients over time, both cognitively and functionally, but without increasing atrophy.

Highlights: Patients at a very prodromal stage, subjective cognitive impairment or mild cognitive impairment, had a clinical diagnosis of either prodromal Alzheimer's disease (Pro-AD), prodromal dementia with Lewy bodies (Pro-DLB), Pro-DLB+AD, or no diagnosis.Amyloid beta positive (Aβ+) patients had more functional decline, whatever the group.Aβ+ DLB patients (Pro-DLB and Pro-DLB+AD) had more global cognitive (Mini-Mental State Examination) decline.Aβ+ Pro-AD patients showed a greater volume decline of the left insula.

Keywords: Alzheimer's disease; amyloid; dementia with Lewy bodies; mild cognitive impairment; prodromal; subjective cognitive impairment.

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Conflict of interest statement

F.B. was the national coordinator for France for the Eisai Delphia (E2027), Axovant Headway‐DLB, and Roche Graduate therapeutic trials; he had received honoraria from Roche, Eisai, and Biogen for oral presentations and from Eisai for a board. The other authors declare that they have no competing interests related to the present work. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Global cognition (MMSE), functional (CDR‐SoB), and quality of life (EQ‐5D) evolution according to amyloid status (purple amyloid positive, green amyloid negative) in the four groups: prodromal dementia with Lewy bodies (Pro‐DLB group), prodromal Alzheimer's disease (Pro‐AD group), prodromal dementia with Lewy bodies and Alzheimer's disease (Pro‐DLB+AD group), and other prodromal patients (NS group). CDR‐SoB, Clinical Dementia Rating Sum of Boxes; MMSE, Mini‐Mental State Examination; NS, no symptom.
FIGURE 2
FIGURE 2
Cognitive evolution for specific tests according to amyloid status (purple amyloid positive, green amyloid negative) in the four groups: prodromal dementia with Lewy bodies (Pro‐DLB group), prodromal Alzheimer's disease (Pro‐AD group), prodromal dementia with Lewy bodies and Alzheimer's disease (Pro‐DLB+AD group), and other prodromal patients (NS group). These tests assess memory (verbal memory for RL/RI‐16, visual memory for Rey figure recall), executive function, and speed processing for TMT‐B, and language and executive function for phonemic fluency and semantic fluency. FCSRT, Free and Cued Selective Reminding Test; NS, no symptom; RL/RI‐16, Rappel Libre Rappel Indicé 16 items; TMT‐B, Trail‐Making Test Part B.
FIGURE 3
FIGURE 3
Slopes of brain MRI regions of interests, brain parenchymal fraction, and white matter hyperintensities according to the amyloid status (purple amyloid positive, green amyloid negative) in the four groups of patients: prodromal dementia with Lewy bodies (Pro‐DLB group), prodromal Alzheimer's disease (Pro‐AD group), prodromal dementia with Lewy bodies and Alzheimer's disease (Pro‐DLB+AD group), and other prodromal patients (NS group). MRI, magnetic resonance imaging; NS, no symptom; SD, standard deviation.
FIGURE 4
FIGURE 4
Slopes of brain FDG PET regions of interests, brain parenchymal fraction, and white matter hyperintensities according to the amyloid status (purple amyloid positive, green amyloid negative) in the four groups of patients: prodromal dementia with Lewy bodies (Pro‐DLB group), prodromal Alzheimer's disease (Pro‐AD group), prodromal dementia with Lewy bodies and Alzheimer's disease (Pro‐DLB+AD group), and other prodromal patients (NS group). FDG PET, fluorodeoxyglucose positron emission tomography; NS, no symptom; SD, standard deviation.
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