Dual time-point [¹⁸F]florbetaben PET delivers dual biomarker information in mild cognitive impairment and Alzheimer’s dementia

Objectives: In 2011, new diagnostic criteria for Alzheimer’s dementia (AD, McKhann et al.) and mild cognitive impairment due to AD (MCI, Albert et al.) were published which were recently supplemented by research criteria for preclinical Alzheimer’s disease (Dubois et al. 2016). All these criteria share the implementation of biomarkers. Recently, we demonstrated that dual time-point [¹⁸F]florbetaben (FBB) PET is able to deliver both blood flow and amyloid load surrogates. The aim of this present study was to investigate whether these surrogates can be utilized as AD biomarkers.

Methods: 112 subjects (age 72±10yrs, ♀:53), n=41 with the clinical diagnosis of MCI, n=50 with probable/possible AD and n=21 with other dementia, underwent dual time-point (0-10min and 90-110min p.i.) FBB PET (hybrid mMR PET/MRI). The PET data were each visually analyzed by 3 experts and semi-quantitatively using Herholz scores for the early and composite SUVRs for the late PET images.

Results: The visual analysis revealed AD-typical patterns in the early images in 35% of all subjects and Aβ-positivity in the late images in 37% of all subjects. For the probable/possible AD cases, the MCI, and the other dementia cases these were 42%/42%, 27%/29%, and 33%/ 38%, respectively. 17% of the MCI subjects were categorized as “MCI due to AD-high likelihood”. Furthermore, 44% of the probable AD subjects were evaluated as “probable AD with high evidence of AD pathophysiological process” and 28% of the patients with possible AD as “possible AD with evidence of AD pathophysiological process”. 27% of all patients showed a positive diagnostic as well as a positive progression biomarker according to the IWG 2 criteria (Dubois et al. 2016). The Herholz scores were significantly lower (0.85±0.05 vs. 0.88±0.04, p=0.015) for the probable/possible AD cases vs. the MCI subjects. Furthermore, the composite SUVRs were significantly higher (1.65±0.23 vs. 1.15±0.17, p<0.005) in the patients visually assessed as Aβ-positive vs. Aβ-negative. A positive linear correlation was found between the Herholz scores and the MMSE scores (R=0.304 p=0.006), but not between the composite SUVRs and the MMSE scores.

Conclusion: The biomarker information provided by dual time-point FBB PET enables to categorize MCI subjects and AD patients according to the recommended diagnostic criteria of the NIA-AA and IWG-2 workgroups. Thus, dual time-point FBB PET has a great potential to supplement diagnostic dementia workups. Research Support: Piramal Imaging, German Research Council