Associations between cerebral blood transit time, amyloid‐β pathology and cognitive decline in non‐demented older adults

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.