Geoffroy Gagliardi1,2, Stéphane Epelbaum1,2,3, Marion Houot2,4, Hovagim Bakardjian1,2, Laurie Boukadida1,2, Marie Revillon1,2, Bruno Dubois1,2,4, Gianfranco Dalla Barba1,2,5, Valentina La Corte2,6,7. 1. Sorbonne Universités, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle (ICM) - Hôpital Pitié-Salpêtrière, Paris, France. 2. 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. 3. Inria, Aramis Project Team, Paris, France. 4. Centre of excellence of neurodegenerative disease (CoEN), ICM, CIC Neurosciences, APHP Department of Neurology, Hopital Pitié-Salpêtrière, University Paris 6, Paris, France. 5. Dipartimento di Scienze della Vita, Universitá degli Studi di Trieste, Trieste, Italy. 6. Memory and Cognition Laboratory, Institute of Psychology, University of Paris Descartes, Paris, France. 7. Center for Psychiatry & Neuroscience, INSERM U894, Paris, France.
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.
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.
Authors: Sigan L Hartley; Benjamin L Handen; Darlynne Devenny; Dana Tudorascu; Brianna Piro-Gambetti; Matthew D Zammit; Charles M Laymon; William E Klunk; Shahid Zaman; Annie Cohen; Bradley T Christian Journal: Alzheimers Dement (Amst) Date: 2020-09-13
Authors: Yu-Hui Liu; Jun Wang; Qiao-Xin Li; Christopher J Fowler; Fan Zeng; Juan Deng; Zhi-Qiang Xu; Hua-Dong Zhou; James D Doecke; Victor L Villemagne; Yen Ying Lim; Colin L Masters; Yan-Jiang Wang Journal: Sci Adv Date: 2021-01-01 Impact factor: 14.136
Authors: Matthew D Zammit; Charles M Laymon; Dana L Tudorascu; Sigan L Hartley; Brianna Piro-Gambetti; Sterling C Johnson; Charles K Stone; Chester A Mathis; Shahid H Zaman; William E Klunk; Benjamin L Handen; Ann D Cohen; Bradley T Christian Journal: Alzheimers Dement (Amst) Date: 2021-01-13
Authors: Sigan L Hartley; Benjamin L Handen; Dana Tudorascu; Laise Lee; Annie Cohen; Brianna Piro-Gambetti; Matthew Zammit; William Klunk; Charles Laymon; Shahid Zaman; Beau M Ances; Marwan Sabbagh; Bradley T Christian Journal: Alzheimers Dement (Amst) Date: 2022-04-01