Amyloid deposition, hypometabolism, and longitudinal cognitive decline.

TLDR: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, cross‐sectional relationships between amyloid deposition, hypometabolism, and cognition are examined.

Abstract: The emergence of positron emission tomography (PET) for imaging fibrillar β-amyloid (Aβ) in vivo is a critical development in the study of Alzheimer disease (AD). Recent amyloid PET studies have raised important questions about how amyloid deposition influences cognitive trajectories, particularly early in the course of disease. Determining the consequences of Aβ at different phases of disease and the relationship between Aβ and other well-known biomarkers of AD such as 18F-fluorodeoxyglucose (FDG) remain important questions that will contribute to our understanding of the clinical relevance of amyloid PET imaging and the development of effective therapies for AD. Hypometabolism, measured with FDG-PET, is associated with cognitive decline1 and conversion from mild cognitive impairment (MCI) to AD.2,3 Recent work has demonstrated that the presence of amyloid is also associated with decline4,5 and conversion.6,7 Integrating data from a variety of sources, researchers have proposed that the time course of Aβ deposition and hypometabolism depends on disease stage,8–10 such that amyloid deposition precedes synaptic and neuronal dysfunction, which is in turn followed by cognitive decline. This model has been supported by several studies comparing the 2 PET measurements with respect to longitudinal decline,11,12 but this work has been limited by small sample sizes and access to patients at different phases of disease. In this study, FDG-PET and amyloid PET data acquired through the Alzheimer’s Disease Neuroimaging Initiative (ADNI) made it possible to compare these measurements in a large sample at different levels of disease severity. [18F]Florbetapir is a PET ligand that has been recently added to the ADNI imaging protocol, and has been validated in a study demonstrating close correspondence between cortical amyloid deposition measured with florbetapir in end-of-life patients and immunohistochemistry measurements of fibrillar Aβ at autopsy.13 We examined cross-sectional relationships between Aβ (measured with florbetapir), hypometabolism (measured with FDG-PET), and cognitive performance (measured with the cognitive subscale of the Alzheimer’s Disease Assessment Scale [ADAS-cog]) in the ADNI population. A subset of the normal and MCI participants had retrospective longitudinal cognitive performance data available. Examining PET measurements (florbetapir, FDG) and cognitive change over time in these 2 diagnostic groups (normal, MCI) allowed us to test the hypothesis that amyloid deposition precedes hypometabolism and both are linked to longitudinal decline.