Helmet T. Karim ^1* Maria Ly ² Gary Yu ² Sang Joon Son ³ Tharick Pascoal ¹

• ¹ University of Pittsburgh, Pittsburgh, United States
• ² Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, United States
• ³ School of Medicine, Ajou University, Suweon, Gyeonggi, Republic of Korea

Introduction: Brain age is a machine learning-derived estimate that captures lower brain volume. Previous studies have found that brain age is significantly higher in mild cognitive impairment and Alzheimer's disease (AD) compared to healthy controls. Few studies have investigated changes in brain age longitudinally in MCI and AD. We hypothesized that individuals with MCI and AD would show heightened brain age over time and across the lifespan. We also hypothesized that both MCI and AD would show faster rates of brain aging (higher slopes) over time compared to healthy controls. Methods: We utilized data from an archival dataset, mainly Alzheimer's disease Neuroimaging Initiative (ADNI) 1 with 3Tesla (3T) data which totaled 677 scans from 183 participants. We predicted brain age using a pre-trained model and tested for accuracy. We conducted longitudinal modeling of age and brain age by group using time from baseline in one model and chronological age in another model.Results: We predicted brain age with a mean absolute error (MAE) < 5 years. Brain age was associated with age across the study and individuals with MCI and AD had greater brain age on average. We found that the MCI group had significantly higher rates of change in brain age over time compared to the HC group regardless of individual chronologic age, while the AD group did not differ in rate of brain age change.Discussion: We replicated past studies that showed that MCI and AD had greater brain age than HC. We additionally found that this was true over time, both groups showed higher brain age longitudinally. Contrary to our hypothesis, we found that the MCI, but not the AD group, showed faster rates of brain aging. We essentially found that while the MCI group was actively experiencing faster rates of brain aging, the AD group may have already experienced this acceleration (as they show higher brain age). Individuals with MCI may experience higher rates of brain aging than AD and controls. AD may represent a homeostatic endpoint after significant neurodegeneration.