Incremental value of amyloid-PET versus CSF in the diagnosis of Alzheimer’s disease

Purpose: To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. Methods: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. Results: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. Conclusions: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. Trial registration: EudraCT no.: 2014-005389-31.