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) [${}^{18}$F]florbetapir PET and T1-weighted MRI scan, enabling calculation of mean binding potential (BP${}_{ND}$; specific amyloid binding) and R${}_1$ (measure of relative (r)CBF). Eighty-three individuals underwent a second [${}^{18}$F]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 R${}_1$ 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 R${}_1$ and BP${}_{ND}$. High baseline BP${}_{ND}$ predicted decline over time in R${}_1$ (all regions, range betas${}_{BP\times time}$ - 0.09 to - 0.14, p < 0.05). Vice versa, low baseline R${}_1$ predicted increase in BP${}_{ND}$ in frontal, temporal, and composite ROIs over time (range betas${}_{R1\times time}$ - 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.