Effect of Mild Cognitive Impairment and APOE Genotype on Resting Cerebral Blood Flow and its Association with Cognition

Using whole-brain pulsed arterial spin labeling magnetic resonance imaging, resting cerebral blood flow (CBF) was measured in 20 mild cognitive impairment (MCI; 11 ε3 and 9 ε4) and 40 demographically matched cognitively normal (CN; 27 ε3 and 13 ε4) participants. An interaction of apolipoprotein (APOE) genotype ( ε3 and ε4) and cognitive status (CN and MCI) on quantified gray-matter CBF corrected for partial volume effects was found in the left parahippocampal and fusiform gyri (PHG/FG), right middle frontal gyrus, and left medial frontal gyrus. In the PHG/FG, CBF was elevated for CN ε4 carriers but decreased for MCI ε4 carriers. The opposite pattern was seen in frontal regions: CBF was decreased for CN ε4 carriers but increased for MCI ε4 carriers. Cerebral blood flow in the PHG/FG was positively correlated with verbal memory for CN ε4 adults ( r=0.67, P=0.01). Cerebral blood flow in the left medial frontal gyrus was positively correlated with verbal memory for MCI ε4 adults ( r=0.70, P=0.05). Findings support dynamic pathophysiologic processes in the brain associated with Alzheimer's disease risk and indicate that cognitive status and APOE genotype have interactive effects on CBF. Correlations between CBF and verbal memory suggest a differential neurovascular compensatory response in posterior and anterior cortices with cognitive decline in ε4 adults.