Vascular alterations have recently gained some attention with their strong association with Alzheimer’s disease (AD). We conducted a label-free in vivo optical coherence tomography (OCT) longitudinal imaging using an AD mouse model. We achieved the tracking of the same individual vessels over time and conducted an in-depth analysis of temporal dynamics in vasculature and vasodynamics using OCT angiography and Doppler-OCT. The AD group showed an exponential decay in both vessel diameter and blood flow change with the critical timepoint before 20 weeks of age, which precedes cognitive decline observed at 40 weeks of age. Interestingly, for the AD group, the diameter change showed the dominance in arterioles over venules, but no such influence was found in blood flow change. Conversely, three mice groups with early vasodilatory intervention did not show any significant change in both vascular integrity and cognitive function compared to the wild-type group. We found early vascular alterations and confirmed their correlation with cognitive impairment in AD.