Table 1.

Cerebral blood flow deficits in the normal aging-to-mild cognitive impairment-to-Alzheimer’s disease spectrum studied with neuroimaging.

	Affected CNS regions	Disease Stages				Methods	References	CBF biomarker prior to			References
		NCI	MCI	Early AD	AD			Brain atrophy	Amyloid	Tau
CBF reductions
Middle cerebral artery territory				C		TCD	51	Yes	Yes	—	2,42,43,51,53,65,66
Precuneus, posterior cingulate, parietotemporal,    frontal and occipital cortices, parahippocampal    gyrus, hippocampus, caudate nucleus, thalamus			C	C		ASL-MRI	56
			C	C			55
			C				59
				C			57
			C	C			58
					C		52
Posterior DMN					C		62
Whole brain					C		61
			C				66
		→ → →					42
Parietotemporal cortices and basal ganglia			C			DSC-MRI	65
Internal carotids and vertebral arteries			C		C	PC-MRI	63
Whole brain			C		C		64
Orbitofrontal, middle and inferiorfrontal, middle    and superior temporal, inferior temporal, and    superior parietal cortices		→				[15O]–PET	67
Impaired cerebrovascular reactivity
Hippocampus		C				BOLD-fMRI (CO2- challenge)	71	—	—	—	2,43
Prefrontal, cingulate and insular cortices				C			69
Middle cerebral artery territory					C	TCD (CO2- challenge)	68
		C					72
Impaired neurovascular coupling
Hippocampal formation			C	C		task-based BOLD-fMRI	73	Yes	—	—	2,43
Visual cortex		C					75

Abbreviations: C, cross-sectional study; →, longitudinal study; —, not studied; CNS, central nervous system; NCI, no cognitive impairment; MCI, mild cognitive impairment; AD, Alzheimer’s disease; CBF, cerebral blood flow; ASL, arterial spin labelling; MRI, magnetic resonance imaging; fMRI, functional MRI; BOLD, blood-oxygenation-level-dependent; DSC, dynamic susceptibility-contrast; PC, phase-contrast; TCD, transcranial Doppler; SPECT, single-photon emission-computed tomography ; PET, positron emission tomography