Recognition memory decline is associated with the progression to prodromal Alzheimer’s disease in asymptomatic at-risk individuals

• Published in: Journal of neurology 2025-01, Vol.272 (1), p.70, Article 70
• Main Authors: Raposo Pereira, Filipa, Chaumon, Maximilien, Dubois, Bruno, Bakardjian, Hovagim, Bahrami, Mahsa, Habert, Marie-Odile, Andrade, Katia, Younsi, Nadjia, La Corte, Valentina, George, Nathalie
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnosis; Alzheimer Disease - physiopathology; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Asymptomatic Diseases; Disease Progression; Female; Humans; Longitudinal Studies; Male; Medicine; Medicine & Public Health; Memory; Memory Disorders - diagnosis; Memory Disorders - etiology; Memory Disorders - physiopathology; Memory, Episodic; Neurodegenerative diseases; Neurology; Neuropsychological Tests; Neuroradiology; Neurosciences; Original Communication; Prodromal Symptoms; Recognition, Psychology - physiology; β-Amyloid
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-024-12834-y

Episodic memory (EM) alterations are a hallmark of Alzheimer’s disease (AD). We assessed EM longitudinally in cognitively normal elders at-risk for AD (with subjective memory complaints), as a function of amyloid-β (Aβ) burden, neurodegeneration (N), and progression to prodromal AD. We stratified 264 INSIGHT-preAD study subjects in controls (Aβ-/N−), stable/N− or N + (Aβ +), and progressors/N− or N + (Aβ +) groups (progressors were included only until AD-diagnosis). We used linear mixed-effect models with Aβ and N status, or progression to AD as factors, to analyze behavioral performance in an old/new word-recognition task based on the free and cued selective reminding test (FCSRT). The controls and stable/N− groups showed near-ceiling accuracy and RT improvement across follow-up. The stable/N + group showed accuracy reduction and no RT improvement, i.e., Aβ + /N + cumulative effect. The progressors showed a marked performance decline. EM alterations may constitute early preclinical markers of progression to prodromal AD, while individuals are cognitively normal according to neuropsychological standards.