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

To compare CSF β-amyloid (Aβ) 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.

A total of 259 CU individuals were categorized as abnormal (+) or normal (-) on CSF Aβ_1-42/Aβ_1-40 analyzed with mass spectrometry and Aβ PET measured with ¹⁸F-florbetapir. Simultaneous longitudinal measurements of CSF and PET were compared for 39 individuals who were unambiguously Aβ-negative at baseline (CSF-/PET-). We also examined the relationship between baseline CSF/PET group membership and longitudinal changes in CSF Aβ, Aβ PET, and cognition.

The proportions of individuals in each discordant group were similar (8.1% CSF+/PET- and 7.7% CSF-/PET+). Among baseline Aβ-negative (CSF-/PET-) individuals with longitudinal CSF and PET measurements, a larger proportion subsequently worsened on CSF Aβ (odds ratio 4 [95% confidence interval (CI) 1.1, 22.1], p = 0.035) than Aβ 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 Aβ 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.

The proportions of discordant PET and CSF Aβ-positive individuals were similar cross-sectionally. However, unambiguously Aβ-negative (CSF-/PET-) individuals are more likely to show subsequent worsening on CSF than PET, supporting the idea that CSF detects the earliest Aβ changes. In discordant cases, only PET abnormality predicted cognitive decline, suggesting that abnormal Aβ PET changes are a later phenomenon in cognitively normal individuals.