Plasma biomarkers of neurodegeneration and intraindividual cognitive variability: Comparing variability across test...

Intraindividual cognitive variability (IICV) is a promising measure for early identification of dementia risk. Fewer studies have assessed IICV using high-frequency digital cognitive assessment or in populations with medical conditions. We aimed to characterize associations between IICV for reaction time and accuracy with plasma biomarkers of neurodegeneration (phosphorylated tau 181, phosphorylated tau 217, β-amyloid 42/40 ratio, glial fibrillary acidic protein, and neurofilament light chain) in individuals with Type 1 diabetes.

We analyzed data from 114 participants from the Glycemic Variability and Fluctuations in Cognitive Status in Adults With Type 1 Diabetes study who provided blood samples (M = 48.9 years, range = 19-84). Cognition was assessed digitally at baseline and three times daily for 15 days via ecological momentary assessment. Hierarchical linear regression models examined associations between biomarkers and IICV, adjusting for demographics, glycemic variability, mean cognition, and nephropathy. Multiple testing correction used Benjamini-Hochberg.

IICVs for reaction time at baseline and across repeated assessments were correlated and associated with β-amyloid 42/40, glial fibrillary acidic protein, neurofilament light chain, and phosphorylated tau 217 (small to moderate effect size, p < .05), but associations did not remain significant after adjustment. Exploratory analyses indicated interactions with age and sex. IICV for accuracy was not associated with any biomarker.

Although associations between IICV and plasma biomarkers were not robust after full adjustment, exploratory analyses suggested potential interactions with age and sex. The sample was predominantly non-Hispanic White, limiting the generalizability of our findings. These findings support continued investigation of digital IICV as a dynamic marker of early cognitive vulnerability. (PsycInfo Database Record (c) 2026 APA, all rights reserved).