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CONCORDANCE BETWEEN CEREBROSPINAL FLUID AMYLOID-β AND [18F]FLORBETABEN PET IN AN UNSELECTED COHORT OF MEMORY CLINIC PATIENTS

      Background

      A decreased amyloid-ß 1-42 (Aß42) in cerebrospinal fluid (CSF) and increased Aß tracer uptake in the brain, as measured using positron emission tomography (PET), could support a clinical diagnosis of Alzheimer’s disease (AD). The purpose of this study was to investigate the concordance between CSF biomarkers and [18F]Florbetaben (FBB) PET in an unselected sample of memory clinic patients.

      Methods

      From March 2015 to November 2016, [18F]FBB PET was offered to all patients visiting our memory clinic. A total of 104 AD patients, 43 non-AD patients, 61 patients with mild cognitive impairment (MCI) and 99 normal controls (NC) with available CSF and [18F]FBB PET were included. CSF biomarkers were considered abnormal when either Aß42 was <640 nl/L or the ration of Aß42 and tau (tau/Aß42 CSF ratio) was > 0.52. [18F]FBB scans were visually rated as normal or abnormal. Concordance between CSF Aß42 and [18F]FBB PET was determined across diagnostic groups. For concordant and discordant cases with abnormal [18F]FBB PET, total tau and ptau were compared within diagnostic groups.

      Results

      Overall concordance between CSF Aß42 and [18F]FBB PET was 81%, and between CSF ratio and [18F]FBB PET it was 88%. When discordant, PET was abnormal in 86% of the cases. Within groups, concordance of CSF Aß42 and [18F]FBB PET was highest for NC (86%), followed by AD (81%), non-AD (81%) and MCI (72%). Concordance between CSF ratio and [18F]FBB PET was higher (AD:91%, MCI:90%, NC:90%, non-AD:81%). There was no difference in CSF total tau and ptau levels between concordant and discordant MCI and AD patients with abnormal [18F]FBB PET (Table 1).

      Conclusions

      In this unselected cohort of memory clinic patients we found a high concordance between CSF Aß42 and [18F]FBB PET. The combination of CSF Aß42 and total tau provided better concordance than Aß42 alone. Discordant MCI and AD patients, based on [18F]FBB PET positivity alone, showed increased CSF total tau and ptau values and Aß42 values near the cut-off, suggesting that borderline CSF Aß42 can already be indicative of underlying AD pathology. Future research should focus on discordant cases to clarify the underlying possibly neuropathological causality.
      Table 1Comparison of concordant and discordant cases within diagnostic groups with abnormal [18F]FBB
      NCNCMCIMCIADAD
      concordantdiscordantconcordantdiscordantconcordantdiscordant
      n91213166418
      Age (±SD)65 ± 664 ± 762 ± 768 ± 665 ± 763 ± 7
      Gender (% male)4 (44%)7 (58%)8 (62%)8 (50%)33 (51%)7 (39%)
      MMSE (±SD)29 ± 427 ± 427 ± 227 ± 222 ± 422 ± 3
      APOE, E4 carrier (%)5 (56%)5 (42%)11 (85%)11 (69%)64 (70%)11 (61%)
      CSF* Aß42 (IQR)594 (73)733 (460)488 (177)732 (197)537 (124)722 (95)
      CSF* total tau (IQR)630 (764)394 (477)619 (217)640 (492)642 (486)680 (546)
      CSF* ptau (IQR)85 (62)60 (57)73 (27)85 (44)81 (41)82 (56)
      NC, normal controls; MCI, mild cognitive impairment; AD, Alzheimer's disease; SD, standard deviation; IQR, interquartile range.
      * median.