The cerebral blood flow response to neuroactivation is reduced in cognitively normal men with β-amyloid accumulation

Background Accumulation of β-amyloid (Aβ) in the brain is a hallmark of Alzheimer’s Disease (AD). Cerebral deposition of Aβ initiates deteriorating pathways which eventually can lead to AD. However, the exact mechanisms are not known. A possible pathway could be that Aβ affects the cerebral vessels, causing inadequate cerebrovascular function. In the present study, we examined if Aβ accumulation is associated with a reduced cerebral blood flow response (CBF) to neuronal activation by visual stimulation (DCBF _Vis.Act ) in cognitively normal subjects from the Metropolit Danish Male Birth Cohort. Methods 64 subjects participated in the present study. DCBF _Vis.Act was measured using arterial spin labelling (ASL) combined with blood-oxygen-level-dependent (BOLD) MRI. Neuronal activation was obtained by visual stimulation by a flickering checkerboard presented on a screen in the MRI-scanner. Brain Aβ accumulation and cerebral glucose metabolism were assessed by PET imaging using the radiotracers [ ¹¹ C]Pittsburgh Compound-B (PiB) and [ ¹⁸ F]Fluorodeoxyglucose (FDG), respectively. Cortical thickness was measured from structural MRI. Results DCBF _Vis.Act correlated negatively (\(\beta\) = -32.1 [95% confidence interval (CI): -60.2 ; -4.1], r = -0.30, p = 0.025) with PiB standardized uptake value ratio (SUVr) in the brain regions activated by visual stimulation. DCBF _Vis.Act did not correlate with FDG SUVr (\(\beta\) = 1.9 [CI: -23.8 ; 27.6], r = 0.02, p = 0.88) or cortical thickness (\(\beta\) = 10.3 [CI: -8.4 ; 29.0], r = 0.15, p = 0.27) in the activated brain regions. Resting CBF did not correlate with PiB SUVr neither in the regions activated by visual stimulation (\(\beta\) = -17.8 [CI:-71.9 ; 36.2], r = 0.09, p = 0.51) nor in the remaining cortex (\(\beta\) = 5.2 [CI:-3.9 ; 14.2], r = 0.15, p = 0.26). Conclusion We found a correlation between high PiB SUVr and reduced CBF response to neuronal activation, indicating a link between Aβ accumulation and impaired cerebrovascular function. The impairment was not associated with cortical thinning or hypometabolism, suggesting that Aβ accumulation affecting brain vessel function could be a very early pathology leading to neurodegenerative disease.