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Alzheimer's Association International Conference 2026
July 12-15, 2026 | London, United Kingdom, and Online
7346
Stage-dependent Changes In Cognitive Intra-individual Variability: The Role Of Amyloid Deposition And Network Segregation
Poster Presenter
Authors
Yura Choi, Dahyun Yi, Woo-Jin Cha, Hyejin Ahn, Gijung Jung, Evgeny Jenya Chumin, Min Soo Byun, Andrew J. Saykin, Kwangsik Nho, Dony Young Lee
Affiliations
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea, Republic of, Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Korea, Republic of, Interdisciplinary program of cognitive science, Seoul National University College of Humanities, Seoul, Korea, Republic of, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA; Indiana Alzheimer’s Disease Research Center, Indiana, University School of Medicine, Indianapolis, IN, USA, Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea, Republic of; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea, Republic of,, Indiana Alzheimer’s Disease Research Center, Indiana, University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; Meidical Neuroscience Graduate Program, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medical and Molecular Genetics, Indiana University School of medicine, Indianapolis, IN, USA,, Indiana Alzheimer’s Disease Research Center, Indiana, University School of Medicine, Indianapolis, IN, USA; Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA; School of Informatics and Computing, Indiana University, Indianapolis, IN, USA, Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea, Republic of; Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, Korea, Republic of; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea, Republic of
Part of Topic
Stage-dependent Changes in Cognitive Intra-individual Variability: The Role of Amyloid Deposition and Network Segregation
Background
Cognitive intra-individual variability (IIV) reflects within-person variability in cognitive performance and is elevated in aging and Alzheimer's disease (AD). Increased cognitive IIV has been proposed as a sensitive marker of cognitive dysfunction beyond mean cognitive performance. However, stage-dependent changes in cognitive IIV and its relationship with AD pathology remain unclear. This study examined stage- and amyloid-related patterns of cognitive IIV and their associations with functional network segregation.
Methods
A total of 515 older adults (CN, MCI, AD dementia; age 55–90 years) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) were included. Participants underwent Korean CERAD assessment, resting-state fMRI, and [¹¹C]PiB-PET imaging. Cognitive IIV was defined as within-person dispersion across neuropsychological test performance independent of global cognition. Test scores were standardized using age-, sex-, and education-adjusted norms, residualized with respect to global cognition (CERAD TS z-score), and summarized as the within-individual standard deviation across cognitive domains. Amyloid positivity was defined as SUVR > 1.4 in any of four predefined cortical regions. Network segregation indices were derived from resting-state fMRI. General linear models were used to examine associations among cognitive IIV, cognitive stage, amyloid positivity, and network segregation.
Results
Cognitive IIV increased across cognitive stages from cognitively normal (CN) to mild cognitive impairment (MCI) and AD dementia. Higher cognitive IIV was associated with lower somatomotor network segregation. Overall, cognitive IIV was modestly higher in amyloid-negative than amyloid-positive individuals after adjusting for age and sex. However, amyloid positivity modified stage-dependent trajectories of cognitive IIV. Among amyloid-negative individuals, cognitive IIV increased from CN to MCI and then plateaued. Among amyloid-positive individuals, cognitive IIV increased progressively from CN to MCI to AD dementia.
Conclusion
Cognitive IIV increased across cognitive stages and was associated with reduced somatomotor network segregation, suggesting a link between cognitive variability and functional brain network organization. Amyloid pathology modified stage-dependent trajectories of cognitive IIV, with progressive increases primarily observed in amyloid-positive individuals. These findings suggest that cognitive IIV may reflect both AD-related pathology and functional brain network alterations.
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