The Memory Binding Test Detects Early Subtle Episodic Memory Decline in Preclinical Alzheimer’s Disease: A Longitudinal Study

Article type: Research Article

Authors: Rapos Pereira, Filipa^{a; b; *} | George, Nathalie^a | Dalla Barba, Gianfranco^c | Dubois, Bruno^{a; b; d} | La Corte, Valentina^{b; e; f} | the INSIGHT-preAD study group

Affiliations: [a] Institut du Cerveau - Paris Brain Institute - ICM, INSERM, U 1127, CNRS, UMR 7225’ APHP, CENIR, Centre MEG-EEG, Sorbonne Université, Hôpital de la Pitié-Salpêtrière, Paris, France | [b] Department of Neurology, Institute of Memory and Alzheimer’s Disease (IM2A), Pitié-Salpêtrière University Hospital, Assistance Publique – Hôpitaux de Paris (AP-HP), Paris, France | [c] Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy | [d] Department of Neurology, Centre of Excellence of Neurodegenerative Disease (CoEN), ICM, CIC Neurosciences, Assistance Publique – Hôpitaux de Paris (AP-HP), Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France | [e] Laboratoire Mémoire Cerveau et Cognition (UR 7536), Institut de Psychologie, Université Paris Cité, Boulogne-Billancourt, France | [f] Institut Universitaire de France, Paris, France

Correspondence: [*] Correspondence to: Filipa Raposo Pereira, Paris Brain Institute, 47 Boulevard de l’Hôpital, Hôpital Pitié-Salpêtrière, Paris, France. E-mail:filipa.raposopereira@icm-institute.org.

Abstract: Background:The asymptomatic at-risk phase might be the optimal time-window to establish clinically meaningful endpoints in Alzheimer’s disease (AD). Objective:We investigated whether, compared with the Free and Cued Selective Reminding Test (FCSRT), the Memory Binding Test (MBT) can anticipate the diagnosis of emergent subtle episodic memory (EM) deficits to an at-risk phase. Methods:Five-year longitudinal FCSRT and MBT scores from 45 individuals matched for age, education, and gender, were divided into 3 groups of 15 subjects: Aβ-/controls, Aβ+/stable, and Aβ+/progressors (preclinical-AD). The MBT adds an associative memory component (binding), particularly sensitive to subtle EM decline. Results:In the MBT, EM decline started in the Aβ+/progressors (preclinical-AD) up to 4 years prior to diagnosis in delayed free recall (FR), followed by decline in binding-associated scores 1 year later. Conversely, in the FCSRT, EM-decline began later, up to 3 years prior to diagnosis, in the same group on both immediate and delayed versions of FR, while on total recall (TR) and intrusions decline started only 1 year prior to diagnosis. Conclusions:The MBT seems more sensitive than the FCSRT for early EM-decline detection, regarding the year of diagnosis and the number of scores showing AD-linked EM deficits (associated with the AD-characteristic amnesic hippocampal syndrome). Considering the MBT as a detection tool of early subtle EM-decline in an asymptomatic at-risk phase, and the FCSRT as a classification tool of stages of EM-decline from a preclinical phase, these tests ought to potentially become complementary diagnostic tools that can foster therapies to delay cognitive decline. Clinical trial registration title: Electrophysiological markers of the progression to clinical Alzheimer disease in asymptomatic at-risk individuals: a longitudinal event-related potential study of episodic memory in the INSIGHT pre-AD cohort (acronym: ePARAD).

Keywords: Alzheimer’s disease, amyloid-β, at-risk, episodic memory, free and cued selective reminding test, memory binding test, preclinical Alzheimer’s disease

DOI: 10.3233/JAD-230921

Journal: Journal of Alzheimer's Disease, vol. 98, no. 2, pp. 465-479, 2024