Hippocampal cerebral blood flow depends on systemic endothelial function in individuals with mild cognitive impairment : the Train the Brain-Mind the vessel study

Background: Dementia has been recently viewed as a predominantly vascular disorder. Indeed, reduced brain NO availability causes increased β-amyloid deposition by several mechanisms, including hypoperfusion. Purpose: To investigate whether a relationship exists between cerebral blood flow in the hippocampal and parahippocampal regions (crucial areas for memory and processing of non-verbal / spatial information) and systemic endothelial function in individuals with mild cognitive impairment (MCI), a subclinical condition predisposing to dementia. Methods: Cerebral blood flow in the hippocampus and parahippocampus (CBF-hipp and CBF-parahipp) were evaluated by magnetic resonance imaging (arterial spin labeling, GE HDxt 1.5 T Signa Neuro-optimized System). Systemic endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery. Results: Complete data about CBF and FMD at enrollment were available for 66 individuals with MCI and 32 without (non-MCI). The two groups were matched for age (75±5 vs 74±5 years respectively, p=0.22), sex (men 45,5% vs 50%, p=0.18) and mean BP (96±10 vs 97±9 mmHg, p=0.41). FMD was significantly lower in MCI than in non-MCI (2.93±2.18 vs 3.74±2.03%, p=0.02); CBF-hipp (64.3±9.43 vs 69.5±7.03 ml/100 gr/min), p=0.002) and CBF-parahipp (66.3±8.02 vs 70.0±8.12 ml/100 gr/min, p=0.002) were significantly lower in MCI as well. Among MCI, FMD was significantly correlated with CBF-parahipp (r=0.26, p=0.03) and CBF-hipp (r=0.32, p=0.009). In a multiple regression model, including age, sex, mean BP, BMI, brachial artery diameter as confounders, FMD remained an independent determinant of CBF-parahipp (beta=0.93, r2=0.063, p=0.04). A similar finding was obtained with CBF-hipp (beta=1.31, r2=0.089, p=0.01). Nor CBF-parahipp (r=-0.13, p=0.48) neither CBF-hipp (r=0.05, p=0.80) were correlated with FMD in non-MCI group. Conclusions: An independent association between hippocampal and parahippocampal CBF and systemic endothelial function is present in individuals with MCI. Acknowledgement/Funding: The study was funded by a grant from Fondazione Cassa di Risparmio di Pisa