Conference on Cognitive Computational Neuroscience

The neuronal sortilin-related receptor (SORL1) expression and function play essential roles in amyloid-beta (Aβ) peptide generation in Alzheimer’s disease (AD). SORL1 gene would also affect multiple Alzheimer’s phenotypes before the clinical onset of symptoms. Here, we analyzed to determine the effect of SORL1 rs2070045, an AD-related polymorphism in Chinese Han population, on cognitive aging, and grey matter atrophy patterns. In this study, 676 non-demented older adults from Beijing Aging Brain Rejuvenation Initiative (BABRI) completed a battery of neuropsychological scales for baseline and ≥ 1 time of follow-up. Structural MRI of 200 subjects were acquired at baseline. We adopted mixed effect model to determine the cognitive decline of rs2070045 polymorphism groups, and found T/T group had a significantly steeper slope of executive function decline, indicating a faster aging in this domain. Then we conducted the atlas-based segmentation strategy to identify the corresponding neurological mechanisms. We didn’t find any volume difference at baseline sMRI indices. We used a machine learning framework to predict executive function aging slope with structural features, and found rs2070045 groups had a specific predictive pattern. rs2070045 risk T/T group has a specific left medial frontal gyrus pattern, which relates to the accelerated executive function decline.