The Contribution of Working Memory Load, Neural Noise, and Alzheimer’s Disease Biomarkers to Age-Related Neural Dedifferentiation

Previous research has found an important relationship between neural noise and age-related neural dedifferentiation (a decline in neural selectivity for unique stimuli or stimuli categories), a phenomenon that has been implicated in cognitive aging and with Alzheimer’s Disease biomarkers. Previous researchers (Koen et al., 2019; Pichot et al., in preparation; Srokova et al., 2020; Simmonite & Polk, 2022) have suggested a need to revise the computational model and resulting simulations of age-related neural dedifferentiation, specifically with regards to working memory load, neural noise, and Alzheimer’s Disease biomarkers across the adult lifespan. This dissertation addressed these gaps in the literature by investigating several crucial contributors to age-related neural dedifferentiation, specifically: (1) individual differences in age-related cognitive function in middle-aged and older adults with varying degrees of Alzheimer’s Disease biomarkers (specifically, APOE e4 genotype, tau burden, and Aß burden), (2) neural selectivity as an index of age-related neural dedifferentiation in EEG ERP studies, (3) the contribution of neural noise to neural dedifferentiation, (4) the contribution of working memory load to neural noise and neural dedifferentiation, and (5) the extent to which individual differences in Alzheimer’s Disease biomarkers relate to or contribute to neural dedifferentiation, as well as the relationship between neural noise and neural dedifferentiation. Using linear effects models, this dissertation examined how working memory load, neural noise, cognitive function, and Alzheimer’s Disease biomarkers relate to age-related neural dedifferentiation in a sample of 46 participants from the Science of Wellness project, a sub-sample from the longitudinal Notre Dame Study of Health & Well-being (NDHWB; Bergeman et al., 2021). Neural selectivity robustly indexed age-related neural dedifferentiation. Increased neural noise contributed to age-related neural dedifferentiation. Individual differences in AD biomarkers contributed to neural noise and age-related neural dedifferentiation. By linking neural noise, working memory load, AD biomarkers, and neural dedifferentiation, I present a promising direction for earlier AD detection and a possible intervention target worth further exploration.