Linking Cognitive Variability and Alzheimers Disease Biomarkers by Neurocognitive Status

Abstract Objective To assess intra-individual cognitive variability (IICV) in relation to Alzheimer’s Disease (AD) biomarkers. Methods The sample included 879 adults from the National Alzheimer’s Coordinating Center, aged 50 and above with a complete neuropsychological evaluation and AD biomarker data available (64% cognitively intact; 36% cognitively impaired). We conducted a series of moderated regression models where AD biomarkers, neurocognitive status, and their interaction effects predicted IICV. IICV measures included demographically adjusted normed scores for the intraindividual standard deviation (iSD) and coefficient of variance (CoV). AD biomarkers included cerebrospinal fluid (CSF) measures of Aβ 1-42 , phosphorylated tau 181 (p-Tau 181 ), and total tau (t-Tau), as well as amyloid positron emission tomography (PET; with both continuous centiloid values and a dichotomous variable). Results Increased AD biomarker burden was associated with increased IICV among cognitively impaired individuals (correlational strength ranging from .206 to .391 for iSD and from .149 to .460 for CoV) but not among the cognitively intact group (correlational strength ranging from .008 to .085 for iSD and from .016 to .085 for CoV). The pattern of results held even after controlling for demographic factors and was comparable in magnitude to the association between AD biomarkers and mean cognitive performance. Conclusions Increases in measures of amyloid, soluble tau, and neurodegeneration are associated with increased IICV among cognitively impaired older adults. The findings underscore the potential of IICV as a sensitive outcome measure in the AD clinical disease phase. Future studies should replicate findings longitudinally and in more diverse samples.