Association of CSF Aβ, amyloid PET, and cognition in cognitively unimpaired elderly adults

Objective To compare CSF beta-amyloid (A beta) and florbetapir PET measurements in cognitively unimpaired (CU) elderly adults in order to detect the earliest abnormalities and compare their predictive effect for cognitive decline. Methods A total of 259 CU individuals were categorized as abnormal (+) or normal (-) on CSF A beta(1-42)/A beta(1-40) analyzed with mass spectrometry and A beta PET measured with 18F-florbetapir. Simultaneous longitudinal measurements of CSF and PET were compared for 39 individuals who were unambiguously A beta-negative at baseline (CSF-/PET-). We also examined the relationship between baseline CSF/PET group membership and longitudinal changes in CSF A beta, A beta PET, and cognition. Results The proportions of individuals in each discordant group were similar (8.1% CSF+/PET-and 7.7% CSF-/PET+). Among baseline A beta-negative (CSF-/PET-) individuals with longitudinal CSF and PET measurements, a larger proportion subsequently worsened on CSF A beta (odds ratio 4 [95% confidence interval (CI) 1.1, 22.1], p = 0.035) than A beta PET over 3.5 +/- 1.0 years. Compared to CSF-/PET-individuals, CSF+/PET-individuals had faster (estimate 0.009 [95% CI 0.005, 0.013], p < 0.001) rates of A beta PET accumulation over 4.4 +/- 1.7 years, while CSF-/PET+ individuals had faster (estimate-0.492 [95% CI-0.861,-0.123], p = 0.01) rates of cognitive decline over 4.5 +/- 1.9 years. Conclusions The proportions of discordant PET and CSF A beta-positive individuals were similar crosssectionally. However, unambiguously A beta-negative (CSF-/PET-) individuals are more likely to show subsequent worsening on CSF than PET, supporting the idea that CSF detects the earliest A beta changes. In discordant cases, only PET abnormality predicted cognitive decline, suggesting that abnormal A beta PET changes are a later phenomenon in cognitively normal individuals.