Discordance and Concordance Between Cerebrospinal and [18F]FDG-PET Biomarkers in Assessing Atypical and Early-Onset AD Dementia Cases
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Abstract
Background and Objectives To assess the concordance and discordance between the core Alzheimer disease (AD) CSF biomarkers and [18F]fluorodeoxyglucose (FDG)-PET patterns evaluated clinically in memory clinic patients who meet appropriate use criteria for AD biomarker investigations.
Methods We retrospectively assessed participants with atypical and/or early-onset dementia evaluated at a tertiary care memory clinic. All individuals underwent CSF evaluations for Aβ42, phosphorylated tau (P-tau181) and total tau, and brain [18F]FDG-PET. [18F]FDG-PET data were visually interpreted by 2 nuclear medicine experts as being consistent with AD or non-AD. CSF biomarker results were similarly grouped into AD biomarker positive/negative. Contingency tables and Kappa coefficients were used to establish the level of agreement and disagreement between CSF and [18F]FDG-PET results in all individuals.
Results One hundred thirty-six individuals had both [18F]FDG-PET and lumbar puncture performed as part of the early-onset and/or atypical dementia assessments. [18F]FDG-PET showed a pattern suggestive of AD in 43% of patients, while CSF biomarkers showed results consistent with AD in 57% of participants. In patients who met criteria for AD biomarker investigations, we found that [18F]FDG-PET was discordant with CSF AD biomarkers in nearly 20% of cases; 12% of individuals with [18F]FDG-PET scans consistent with AD had AD-negative CSF results; and 7% of individuals with [18F]FDG-PET scans not consistent with AD had AD-positive CSF results, potentially suggesting atypical AD variants or less advanced neurodegeneration. [18F]FDG-PET discriminated patients with an AD-positive CSF profile from patients with an AD-negative profile with a sensitivity and specificity higher than 80% (sensitivity: 81%, 95% CI = 71–88%, SP: 81%, 95% CI = 68–89%). Furthermore, [18F]FDG-PET had a positive predictive value of 87% (95% CI = 78–93%) and a negative predictive value of 72% (95% CI = 60–82%).
Discussion CSF and [18F]FDG-PET disagreed in nearly 20% of the cases studied in this clinical series. While CSF Aβ42 and P-tau181 biomarkers are specific for AD, the topographical information from [18F]FDG-PET may provide complementary information.
Glossary
- Aβ=
- amyloid-β;
- AD=
- Alzheimer disease;
- ATI=
- Aβ42 to T-tau index;
- FDG=
- Fluorodeoxyglucose;
- FTLD=
- frontal temporal lobar degeneration;
- IQR=
- interquartile range;
- MCI=
- mild cognitive impairment;
- MCSA=
- McGill University Research Center for Studies in Aging;
- MMSE=
- Mini Mental State Examination;
- MoCA=
- Montreal Cognitive Assessment;
- P-tau181=
- phosphorylated tau;
- T-tau=
- total tau
Footnotes
↵* These authors contributed equally as first authors.
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Submitted and externally peer reviewed. The handling editor was Rawan Tarawneh, MD.
Editorial, page 973
- Received October 14, 2021.
- Accepted in final form July 19, 2022.
- © 2022 American Academy of Neurology
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