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Hybrid PET/MRI Imaging of Alzheimer's Disease Based on 18F-AV-1451
Published on: April 18, 2025
Amyloid negativity in patients with clinically diagnosed Alzheimer disease and MCI
Susan M Landau1, Andy Horng2, Allison Fero2
1From Helen Wills Neuroscience Institute (S.M.L., A.H., W.J.J.), University of California, Berkeley; and Life Sciences Division (S.M.L., A.F., W.J.J.), Lawrence Berkeley National Laboratory, CA. slandau@berkeley.edu.
Objective:
To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a prospective cohort study.
Methods:
We first investigated the reliability of florbetapir- PET in patients with AD and patients with MCI using CSF-Aβ1-42 as a comparison amyloid measurement. We then compared florbetapir- vs florbetapir+ patients with respect to several AD-specific biomarkers, baseline and longitudinal cognitive measurements, and demographic and clinician report data.
Results:
Florbetapir and CSF-Aβ1-42 +/- status agreed for 98% of ADs (89% of MCIs), indicating that most florbetapir- scans were a reliable representation of amyloid status. Florbetapir- AD (n = 27/177; 15%) and MCI (n = 74/217, 34%) were more likely to be APOE4-negative (MCI 83%, AD 96%) than their florbetapir+ counterparts (MCI 30%, AD 24%). Florbetapir- patients also had less AD-specific hypometabolism, lower CSF p-tau and t-tau, and better longitudinal cognitive performance, and were more likely to be taking medication for depression. In MCI only, florbetapir- participants had less hippocampal atrophy and hypometabolism and lower functional activity questionnaire scores compared to florbetapir+ participants.
Conclusions:
Overall, image analysis problems do not appear to be a primary explanation of amyloid negativity. Florbetapir- ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts, suggesting that one or more non-AD etiologies (which may include vascular disease and depression) account for their AD-like phenotype.
Insights
Amyloid-negative Alzheimer disease (AD) and mild cognitive impairment (MCI) patients show distinct clinical and biomarker profiles. These findings suggest non-AD causes for their AD-like symptoms.
Area of Science:
- Neurology
- Neuroimaging
- Biomarkers
Background:
- Alzheimer disease (AD) diagnosis relies on amyloid (Aβ) detection.
- Amyloid-negative cases present a diagnostic challenge.
- Understanding these cases is crucial for accurate diagnosis and treatment.
Purpose of the Study:
- To characterize amyloid-negative AD and mild cognitive impairment (MCI) patients.
- To compare clinical and biomarker data between amyloid-negative and amyloid-positive individuals.
- To investigate the reliability of florbetapir-PET for amyloid assessment.
Main Methods:
- Utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
- Assessed florbetapir-PET and cerebrospinal fluid (CSF) Aβ1-42 for amyloid status.
- Compared biomarkers, cognitive performance, and demographics between florbetapir-PET negative and positive groups.
Main Results:
- Florbetapir-PET and CSF Aβ1-42 showed high agreement for amyloid status.
- Amyloid-negative AD/MCI patients were more likely APOE4-negative.
- Florbetapir-negative individuals exhibited less AD-specific hypometabolism, lower tau levels, and better cognitive trajectories.
Conclusions:
- Image analysis issues are unlikely to explain amyloid negativity.
- Amyloid-negative ADNI patients possess unique clinical and biomarker features.
- Non-AD etiologies, such as vascular disease or depression, may underlie AD-like phenotypes in these patients.
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