Cognitive dispersion in the Alzheimer’s disease spectrum
Justine Marsault, Guillaume T. Vallet, Sven Joubert,Abstract
Objectives:
Subjective cognitive decline (SCD) may represent the earliest observable stage of Alzheimer’s disease (AD), yet identifying individuals at risk of progressing remains challenging. Cognitive dispersion, or intra-individual variability (IIV-D), may serve as a sensitive early marker. This study examined IIV-D across diagnostic groups, focusing on SCD and amnestic mild cognitive impairment (aMCI) progressors (SCD-p, aMCI-p; progressing to a more advanced disease stage) versus non-progressors (SCD-np, aMCI-np; not progressing to a more advanced stage). We expected greater IIV-D across groups (AD > aMCI > SCD > controls) and in progressors.
Methods:
A total of 308 participants aged 65–94 (67 healthy controls [HC], 126 SCD, 79 aMCI, 36 AD) from the Consortium for the Early Identification of Alzheimer’s Disease – Quebec (CIMA-Q) were included. SCD and aMCI participants were followed for up to eight years (34 SCD-p, 92 SCD-np; 29 aMCI-p, 50 aMCI-np). Analyses of covariance assessed baseline across- and verbal memory within-domain IIV-D, maximum discrepancy (MD), and domain-specific deviation.
Results:
IIV-D increased with disease severity (HC = SCD < aMCI < AD). Among SCD participants, progressors showed greater episodic memory deviation than non-progressors, primarily driven by poorer Logical Memory delayed recall. In aMCI, progressors showed higher IIV-D across all indices (across- and within-domain, IIV-D and MD), with domain-specific differences limited to episodic memory.
Conclusions:
These findings indicate that IIV-D measures distinguish aMCI progressors from non-progressors, although they do not appear to enhance predictive accuracy for progression to AD and may not yet be a reliable marker at the SCD stage.