Cerebral blood flow in mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis

Background: Reduced cerebral blood flow (CBF) contributes to the pathophysiology of Alzheimer's disease (AD). However, it is unclear whether there is a spatial-temporal-specific pattern of changed CBF in AD progression. Methods: We systematically screened literature databases for cross-sectional and longitudinal studies reporting resting CBF or CBF velocity (CBFv) among patients with AD, mild cognitive impairment (MCI), and healthy controls (HCs). Standardised mean differences (SMDs) for CBF and mean differences (MDs) for CBFv were calculated. Quality assessments, meta-analysis, subgroup analysis, and meta-regression were subsequently performed (PROSPERO: CRD42020207548). Results: Overall, 244 studies comprising 13,644 participants and 60 regions were included. Compared with HCs, AD subjects had decreased resting CBF throughout the brain (SMD range: -1.87 to -0.32), especially within the posterior cingulate and temporal-parietal regions. However, MCI subjects presented decreased CBF in ten regions with modest effects (SMD range: -0.86 to -0.25), especially in the precuneus. We identified the decreased CBF in the temporal, parietal, and hippocampal regions was associated with the lower AD Mini-Mental State Examination scores. Conclusions: Our findings suggest that the spatial-temporal pattern of CBF decreased from the precuneus, posterior cingulate and temporal-parietal regions to broader areas with progression from HC to MCI to AD, supporting the incorporation of CBF into the AD research framework.