Increased cerebral blood flow is associated with higher baseline amyloid burden in a cognitively unimpaired population

Abstract Background As cerebrovascular and Alzheimer’s proteinopathy have previously shown to affect cerebral blood flow (CBF) as well as cognition, CBF could be a potential early hemodynamic biomarker of cognitive decline. Here, we investigated to what extent cardiovascular risk factors and amyloid burden affect CBF in an elderly cognitively unimpaired (CU) population. Method We included 153 CU participants (minimal MMSE = 28) from the EMIF‐AD PreclinAD Twin60++ cohort ( Table 1) , who underwent [18F]flutemetamol PET and arterial spin labeling (ASL) MRI. Amyloid‐PET scans were visually assessed as negative or positive, upon which participants were grouped based on their longitudinal changes in amyloid positivity (visual read groups). Cortical amyloid burden was quantified with the Centiloid method globally and for 4 early amyloid accumulation regions of interest (ROIs). ASL scans were processed and quantified with ExploreASL for total gray matter (GM), and for vascular territories overlapping with the amyloid ROIs (Figure 1). Longitudinal analysis including baseline Centiloid values and yearly CBF change rates (Delta CBF) was performed for 98 participants with longitudinal imaging data available (4.23 years ± 0.43 follow‐up time). Associations between CBF and amyloid — with and without the interaction of vascular risk factors (i.e., Framingham score) — were assessed using generalized estimating equations (GEEs), both for baseline and rates of change measurements. Models were adjusted for age, sex, and twin dependency. Result While no association between amyloid burden and CBF was observed across the cohort, in participants with a high Framingham vascular risk score, higher amyloid was associated with increased CBF, for most ROIs ( Table 2 , Figure 2 ). Additionally, precuneus amyloid burden was predictive of CBF change in the corresponding vascular territory ( Figure 3 ). Visual reading shows that subjects with high amyloid burden at baseline had a higher increase of CBF at follow‐up (Stable AB+, Figure 4 ). Conclusion We found that the combination of cardiovascular risk and amyloid burden in AD signature regions was associated with increased CBF in CU individuals, which may reflect a vascular or inflammatory compensatory response to early Alzheimer pathology. Future studies may help understanding how these mechanisms affect cognition.