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Published on: June 26, 2013
Differential FDDNP PET patterns in nondemented middle-aged and older adults
Linda M Ercoli1, Prabha Siddarth, Vladimir Kepe
1Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095-9668, USA. lercoli@mednet.ucla.edu
Objective:
The authors explored whether positron emission tomography (PET) with 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl) amino]-2-naphthyl} ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, might identify homogeneous subgroups of persons in middle-aged and older persons with mild cognitive impairment (MCI) or normal cognition.
Participants:
Fifty-six subjects (MCI, N = 29; normal cognition, N = 27).
Measurements:
FDDNP-PET scans were performed. Logan parametric images were produced using cerebellum as a reference region, and relative distribution volumes were obtained for regions of interest (ROIs) known to accumulate plaques and tangles in Alzheimer disease (AD). Cluster analysis was used to identify subgroups of subjects according to FDDNP signal distribution. Once the FDDNP clusters were identified, the authors then characterized the clusters also with respect to diagnosis and cognitive test performances and conducted analyses on cluster differences in these variables.
Results:
The authors identified three FDDNP clusters: high signal in lateral temporal and posterior cingulate ROIs (high temporal-posterior cingulate HT/PC); low signal in all ROIs (low global [LG] cluster); high frontal and parietal signal with intermediate temporal and posterior cingulate signal (HF/PA). Most MCI subjects belonged to the HT/PC and HF/PA clusters, whereas most cognitively normal subjects were in the LG cluster. On cognitive tests, the HT/PC and the HF/PA clusters performed significantly worse than LG but did not significantly differ from each other.
Conclusions:
This approach may be useful in identifying potential high-risk imaging cluster patterns. Longitudinal follow-up would be performed to determine the association of these subgroups with diagnostic and functional outcome.
Insights
Positron emission tomography (PET) with FDDNP may identify distinct subgroups in individuals with mild cognitive impairment (MCI) or normal cognition. These imaging patterns correlate with cognitive performance and could indicate individuals at higher risk.
Area of Science:
- Neuroimaging
- Nuclear Medicine
- Cognitive Neurology
Background:
- Mild cognitive impairment (MCI) and normal cognition represent distinct stages in cognitive aging.
- Identifying homogeneous subgroups within these populations is crucial for understanding disease progression and developing targeted interventions.
- Positron emission tomography (PET) tracers that bind to Alzheimer's disease (AD) pathologies, such as amyloid plaques and tau tangles, offer potential for in vivo stratification.
Purpose of the Study:
- To investigate the utility of FDDNP-PET imaging in identifying distinct subgroups within middle-aged and older adults with MCI or normal cognition.
- To determine if these FDDNP-defined subgroups correlate with diagnosis and cognitive test performance.
Main Methods:
- Fifty-six participants (29 MCI, 27 normal cognition) underwent FDDNP-PET scans.
- Logan parametric analysis was used to generate relative distribution volumes in regions of interest (ROIs) associated with AD pathology.
- Cluster analysis was applied to FDDNP signal distribution to identify subject subgroups, which were then characterized by diagnosis and cognitive function.
Main Results:
- Three distinct FDDNP-PET clusters were identified: high temporal-posterior cingulate (HT/PC), low global (LG), and high frontal-parietal (HF/PA).
- The majority of MCI subjects fell into the HT/PC and HF/PA clusters, while most cognitively normal subjects were in the LG cluster.
- Subjects in the HT/PC and HF/PA clusters demonstrated significantly poorer cognitive performance compared to the LG cluster.
Conclusions:
- FDDNP-PET imaging can differentiate subgroups within populations with MCI and normal cognition based on tracer uptake patterns.
- These imaging-defined subgroups show distinct cognitive profiles, suggesting potential as biomarkers for risk stratification.
- Further longitudinal studies are warranted to validate the association of these FDDNP-PET clusters with diagnostic and functional outcomes.
