Cerebral blood flow, amyloid burden, and cognition in cognitively normal individuals

Purpose: The role of cerebral blood flow (CBF) in the early stages of Alzheimer’s disease is complex and largely unknown. We investigated cross-sectional and longitudinal associations between CBF, amyloid burden, and cognition, in cognitively normal individuals with subjective cognitive decline (SCD). Methods: We included 187 cognitively normal individuals with SCD from the SCIENCe project (65 ± 8 years, 39% F, MMSE 29 ± 1). Each underwent a dynamic (0–70 min) [¹⁸F]florbetapir PET and T1-weighted MRI scan, enabling calculation of mean binding potential (BP_ND; specific amyloid binding) and R₁ (measure of relative (r)CBF). Eighty-three individuals underwent a second [¹⁸F]florbetapir PET (2.6 ± 0.7 years). Participants annually underwent neuropsychological assessment (follow-up time 3.8 ± 3.1 years; number of observations n = 774). Results: A low baseline R₁ was associated with steeper decline on tests addressing memory, attention, and global cognition (range betas 0.01 to 0.27, p < 0.05). High BP_ND was associated with steeper decline on tests covering all domains (range betas − 0.004 to − 0.70, p < 0.05). When both predictors were simultaneously added to the model, associations remained essentially unchanged. Additionally, we found longitudinal associations between R₁ and BP_ND. High baseline BP_ND predicted decline over time in R₁ (all regions, range betas_BP×time − 0.09 to − 0.14, p < 0.05). Vice versa, low baseline R₁ predicted increase in BP_ND in frontal, temporal, and composite ROIs over time (range betas_R1×time − 0.03 to − 0.08, p < 0.05). Conclusion: Our results suggest that amyloid accumulation and decrease in rCBF are two parallel disease processes without a fixed order, both providing unique predictive information for cognitive decline and each process enhancing the other longitudinally.