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

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.

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.

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.

Prolonged blood transit time can reflect early vascular impairment in AD.

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.