Abstract
INTRODUCTION: The contribution of cerebrovascular hemodynamic disturbances to Alzheimer's disease (AD) remains unclear. Using time-shift analysis of blood-oxygenation-level-dependent (BOLD) signals, we explored associations between cerebral blood transit time, amyloid beta (Aβ) pathology, and cognition. METHODS: We included 131 non-demented individuals from the Alzheimer's Disease Neuroimaging Initiative. Three transit metrics - termed Lag(ICA-SSS), Lag(ICA-global), and Lag(global-SSS) - were derived from BOLD time lags between the internal carotid artery (ICA), superior sagittal sinus (SSS), and global signal. Associations between transit metrics, Aβ burden, and cognition were investigated through cross-sectional and longitudinal analyses. RESULTS: At baseline, prolonged Lag(ICA-global) and Lag(ICA-SSS) were associated with higher Aβ burden, while their adverse effect on cognition was largely mediated by Aβ pathology. In longitudinal analyses, prolonged Lag(global-SSS) and Lag(ICA-SSS) predicted faster Aβ accumulation. Synergistic interactions between Lag(ICA-global), Lag(global-SSS), and Aβ burden were linked to accelerated cognitive decline. DISCUSSION: Prolonged blood transit time can reflect early vascular impairment in AD. HIGHLIGHTS: Vascular risks are associated with prolonged arterial transit time (Lag(ICA-global)) and cerebral blood transit time (Lag(ICA-SSS)). Prolonged venous blood transit time (Lag(global-SSS)) and Lag(ICA-SSS) are linked to accelerated Aβ accumulation. Aβ burden mediates the association between prolonged Lag(ICA-global) and Lag(ICA-SSS) and cognitive impairment. Aβ Amyloid burden may interact synergistically with prolonged Lag(ICA-global) and Lag(global-SSS) to exacerbate cognitive decline.