Discordance and Concordance Between Cerebrospinal and [18F]FDG-PET Biomarkers in Assessing Atypical and Early-Onset AD Dementia Cases.

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 Aß42, 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 Aß42 and P-tau181 biomarkers are specific for AD, the topographical information from [18F]FDG-PET may provide complementary information.