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Challenges in Alzheimer's Disease Diagnostic Work-Up: Amyloid Biomarker Incongruences
Challenges in Alzheimer's Disease Diagnostic Work-Up: Amyloid Biomarker Incongruences
- Source :
- Journal of Alzheimer's disease : JAD. 77(1)
- Publication Year :
- 2020
-
Abstract
- Background: Discordance among amyloid biomarkers is a challenge to overcome in order to increase diagnostic accuracy in dementia. Objectives: 1) To verify that cerebrospinal fluid (CSF) Aβ42/Aβ40 ratio (AβR) better agrees with Amyloid PET (Amy-PET) results compared to CSF Aβ42; 2) to detect differences among concordant positive, concordant negative, and discordant cases, basing the concordance definition on the agreement between CSF AβR and Amy-PET results; 3) to define the suspected underlying pathology of discordant cases using in vivo biomarkers. Method: We retrospectively enrolled 39 cognitively impaired participants in which neuropsychological tests, apolipoprotein E genotype determination, TC/MRI, FDG-PET, Amy-PET, and CSF analysis had been performed. In all cases, CSF analysis was repeated using the automated Lumipulse method. In discordant cases, FDG-PET scans were evaluated visually and using automated classifiers. Results: CSF AβR better agreed with Amy-PET compared to CSF Aβ42 (Cohen’s K 0.431 versus 0.05). Comparisons among groups did not show any difference in clinical characteristics except for age at symptoms onset that was higher in the 6 discordant cases with abnormal CSF AβR values and negative Amy-PET (CSF AβR+/AmyPET–). FDG-PET and all CSF markers (Aβ42, AβR, p-Tau, t-Tau) were suggestive of Alzheimer’s disease (AD) in 5 of these 6 cases. Conclusion: 1) CSF AβR is the CSF amyloid marker that shows the better level of agreement with Amy-PET results; 2) The use of FDG-PET and CSF-Tau markers in CSFAβR+/Amy-PET–discordant cases can support AD diagnosis; 3) Disagreement between positive CSF AβR and negative Amy-PET in symptomatic aged AD patients could be due to the variability in plaques conformation and a negative Amy-PET scan cannot be always sufficient to rule out AD.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Amyloid
Concordance
Pilot Projects
tau Proteins
Disease
Neuropsychological Tests
Gastroenterology
03 medical and health sciences
0302 clinical medicine
Cerebrospinal fluid
Alzheimer Disease
Internal medicine
Medicine
Dementia
Humans
Aged
Retrospective Studies
Amyloid beta-Peptides
business.industry
General Neuroscience
Neuropsychology
General Medicine
Middle Aged
medicine.disease
Work-up
Peptide Fragments
Psychiatry and Mental health
Clinical Psychology
030104 developmental biology
Cross-Sectional Studies
Positron-Emission Tomography
Biomarker (medicine)
Female
Geriatrics and Gerontology
business
030217 neurology & neurosurgery
Biomarkers
Subjects
Details
- ISSN :
- 18758908
- Volume :
- 77
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's disease : JAD
- Accession number :
- edsair.doi.dedup.....fa8e5f80b803a74ec08eb71b54ec8c39