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

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 LagICA-SSS, LagICA-global, and Lagglobal-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 LagICA-global and LagICA-SSS were associated with higher Aβ burden, while their adverse effect on cognition was largely mediated by Aβ pathology. In longitudinal analyses, prolonged Lagglobal-SSS and LagICA-SSS predicted faster Aβ accumulation. Synergistic interactions between LagICA-global, Lagglobal-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 (LagICA-global) and cerebral blood transit time (LagICA-SSS). Prolonged venous blood transit time (Lagglobal-SSS) and LagICA-SSS are linked to accelerated Aβ accumulation. Aβ burden mediates the association between prolonged LagICA-global and LagICA-SSS and cognitive impairment. Aβ Amyloid burden may interact synergistically with prolonged LagICA-global and Lagglobal-SSS to exacerbate cognitive decline.