Early functional neuroimaging alterations in pTau217 biomarker-positive older adults

Introduction Early identification of individuals with Alzheimer’s Disease (AD) is key to its successful management. In this regard, plasma biomarkers and functional magnetic resonance imaging alterations could represent useful triage tools for preclinical AD cases. Methods In this study, we analyzed the relationship between neuroimaging, biological and cognitive data from 88 elderly participants recruited from the University Hospital of Padua. Neuroimaging alterations were quantified based on a measure of dispersion within the connectivity gradient. LASSO and multiple linear regression models were used to specifically assess the interaction between gradients’ dispersion and plasma pTau217 levels in predicting cognitive performance, while controlling for cognitive reserve and renal dysfunction. Finally, exploratory ANCOVA models were used to test differences in dispersion between cognitively unimpaired individuals (UC), individuals with mild cognitive impairment (MCI) who were pTau217-negative, individuals with prodromal AD (PR), defined by MCI status and pTau217 positivity, and a group of patients with more advanced AD from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Results Our results show that functional dispersion positively impacts cognitive performance in healthy participants, but only in crossmodal integration hubs and in tasks requiring multimodal processing. In PR individuals, however, dispersion within a wider profile of regions appeared to favor memory performance. Finally, dispersion values within several cortical regions were observed to significantly differ between UC and MCI individuals compared to AD, but not between PR and AD participants. Conclusion Although preliminary, our data delineate patterns of functional alterations in individuals with prodromal AD.