Which Episodic Memory Performance is Associated with Alzheimer’s Disease Biomarkers in Elderly Cognitive Complainers? Evidence from a Longitudinal Observational Study with Four Episodic Memory Tests (Insight-PreAD)

Article type: Research Article

Authors: Gagliardi, Geoffroy^{a; b; *} | Epelbaum, Stéphane^{a; b; c} | Houot, Marion^{b; d} | Bakardjian, Hovagim^{a; b} | Boukadida, Laurie^{a; b} | Revillon, Marie^{a; b} | Dubois, Bruno^{a; b; d} | Dalla Barba, Gianfranco^{a; b; g; 1} | La Corte, Valentina^{b; e; f; 1} | for the INSIGHT-preAD study group

Affiliations: [a] Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM) – Hôpital Pitié-Salpêtrière, Paris, France | [b] Centre de référence pour les maladies d’Alzheimer du sujet jeune et les démences rares, Institut de la mémoire et de la maladie d’Alzheimer, Département de Neurologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France | [c] Inria, Aramis Project Team, Paris, France | [d] Centre of excellence of neurodegenerative disease (CoEN), ICM, CIC Neurosciences, APHP Department of Neurology, Hopital Pitié-Salpêtrière, University Paris 6, Paris, France | [e] Memory and Cognition Laboratory, Institute of Psychology, University of Paris Descartes, Paris, France | [f] Center for Psychiatry & Neuroscience, INSERM U894, Paris, France | [g] Dipartimento di Scienze della Vita, Universitá degli Studi di Trieste, Trieste, Italy

Correspondence: [*] Correspondence to: Geoffroy Gagliardi, Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM) - Hôpital Pitié-Salpêtrière, Paris, France. E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Alzheimer’s disease (AD) pathology is found in the brain years before symptoms are usually detected. An episodic memory (EM) decline is considered to be the specific cognitive sign indicating a transition from the preclinical to the prodromal stage of AD. However, there is still no consensus on the most sensitive tool to detect it. Objective:The goal of our study was to determine which EM measures, among three clinically used EM tests and one research EM test, would be optimal to use for detection of early decline in elderly cognitive complainers. Methods:318 healthy elderly participants with subjective cognitive complaint were followed for two years. We applied generalized linear mixed models to investigate the effect of baseline brain amyloid and metabolism on the longitudinal evolution of four EM tests. Results:Our findings show that participants performed significantly worse in two out of four EM tests (i.e., the Memory Binding Test and the Delayed Matched Sample test 48 items) as their level of brain amyloid load increased. However, we did not find an association between EM measures and brain metabolism. An interaction of the two biomarkers was associated with the number of intrusions in the Memory Binding Test over two years. Conclusion:As most clinical trials in AD are now including patients at its early clinical stage, the precise delineation of the transition phase between the preclinical and prodromal stages of the disease is of crucial importance. Our study indicates that challenging EM tests and intrusions are valuable tools to identify this critical transition.

Keywords: Alzheimer’s disease, biomarkers, cognition, episodic memory, preclinical

DOI: 10.3233/JAD-180966

Journal: Journal of Alzheimer's Disease, vol. 70, no. 3, pp. 811-824, 2019