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

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).

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).

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).

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.