Abstract
Age-related changes in cerebral blood flow (CBF), which carries necessary nutrients to the brain, are associated with increased risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Whether the association between CBF and cognition is moderated by apolipoprotein E (ApoE) ε4 genotype, a known risk factor for AD, remains understudied, with most research focusing on exploring brain regions in which there are diagnostic group differences in CBF (i.e., cognitively normal vs. MCI vs. AD). This study measured resting CBF via arterial spin labeling (ASL) magnetic resonance imaging (MRI) and verbal memory functions using a composite score in 59 older adults with normal cognition (38 ε3; 21 ε4). Linear mixed effect models were employed to investigate if the voxel-wise relationship between verbal memory performance and resting CBF was modified by ApoE genotype. Results indicated that carriers of the ApoE ε4 allele display negative associations between verbal memory functions and CBF in medial frontal cortex, medial and lateral temporal cortex, parietal regions, insula, and the basal ganglia. Contrarily, ε3 carriers exhibited positive associations between verbal memory functions and CBF in medial frontal cortex, thalamus, insula, and basal ganglia. Findings suggest that higher CBF was associated with worse verbal memory functions in cognitively normal ε4 carriers, perhaps reflecting dysregulation within the neurovascular unit, which is no longer supportive of cognition. Results are discussed within the context of the vascular theory of AD risk.
Highlights
Normal aging is associated with decrements in cognitive function and changes in markers of brain health, such as reductions in cerebral blood flow (CBF; Parkes et al, 2004; Lu et al, 2011)
Significant interactions between apolipoprotein E (ApoE) genotype and verbal memory composite scores on CBF were found in nine clusters within locations consistent with distributed verbal memory processing (Grasby et al, 1993): right anterior cingulate cortex (ACC), left thalamus, left hippocampus and parahippocampal gyrus (PHG), left insula and putamen, left middle temporal gyrus (MTG), right putamen and globus pallidus (GP; lenticular nucleus), right middle and superior temporal gyrus (STG), left supramarginal gyrus (SMG), and the left lingual gyrus (LG)
Within these nine clusters there was a trend for the ApoE+ genotype group to display overall lower CBF than the ApoE− group (Figure 1), with significant group differences in the left MTG (ApoE− mean CBF = 70.6, ApoE+ mean CBF = 58.2, p = 0.027) and the right middle and STG (APOE− mean CBF = 70.4, APOE+ mean CBF = 51.8, p = 0.011)
Summary
Normal aging is associated with decrements in cognitive function and changes in markers of brain health, such as reductions in cerebral blood flow (CBF; Parkes et al, 2004; Lu et al, 2011). CBF, the rate of delivery of arterial blood to the capillary bed of a tissue, is a measure of brain metabolism and neural function. Previous studies investigating the associations between cognition and global gray matter (GM) CBF in cognitively normal older adults report mixed results, with some showing positive associations using carotid and basilar arterial flow measurements (Rabbitt et al, 2006) and others finding negative correlations using continuous ASL MRI (Bertsch et al, 2009). These research findings are encouraging and warrant further investigation of the direct associations between cognition and CBF and their possible clinical implications for Alzheimer’s disease (AD) prevention
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