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

Objective: To assess the concordance and discordance between the core Alzheimer’s disease (AD) CSF biomarkers and [¹⁸F]FDG-PET patterns evaluated clinically in memory clinic patients who meet appropriate use criteria for AD biomarker investigations.

Methods: We retrospectively assessed subjects with atypical and/or early-onset dementia evaluated at a tertiary care memory clinic. All individuals underwent CSF evaluations for Aβ42, P-tau181 and T-tau, and brain [¹⁸F]FDG-PET. [¹⁸F]FDG-PET data was visually interpreted by two 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: 136 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 subjects. 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% (SN: 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.