Investigating the associations between regional tau burden measured using [F18]‐MK6240 positron emission tomography, clinical and cognitive outcomes

Abstract Background The recent development of positron emission tomography (PET) radiotracers for tau aggregates allows visualizing tau pathology in vivo . The aim of this study was to investigate the associations between regional tau‐PET binding, measured using [18F]‐MK6240, a promising second‐generation tau‐PET tracer, and clinical and cognitive outcomes. Method 125 participants were recruited between June 2019 and April 2022 at the Memory Clinic of Saint‐Luc University Hospital. Each participant underwent [ F18]‐MK6240 tau‐PET, MRI, cognitive assessment, and either lumbar punction or [F18]‐Flutemetamol amyloid‐PET. A visual read of tau‐PET images was performed according to the Braak stage classification. Tau‐PET imaging data were also quantitatively processed using PMOD‐Neuro tools and Freesurfer. Cognition was assessed using four composite scores evaluating memory, language, executive and visuospatial functions. Result Braak 0 visual reads included 12 cognitively unimpaired, 7 SCI, 5 MCI due to AD (MCI AD), and 7 non‐AD patients (Fig.1). The number of MCI AD cases ranged from Braak 0 to Braak 5 categories, while the number of patients with AD dementia ranged from Braak 4 to Braak 6. Only 3 non‐AD cases had positive scans (1 APP Aβ‐, 1 FTLD, 1 PART). On average, in Braak 0‐2 cases, all cognitive composite scores were in the normal range (Fig.2). In Braak 3‐4 cases, only episodic memory was impaired, while in Braak 5‐6 cases all cognitive domains were impaired. Conclusion Visual Braak staging of [ F18]‐MK6240 PET images matches clinical diagnosis of MCI, AD dementia and non‐AD dementia. Moreover, cases with neocortical temporal uptake (Braak 3‐4) accordingly presented isolated episodic memory, while cases with extensive neocortical uptake (Braak 5‐6) were impaired in almost all cognitive domains. Correlational analyses are currently ongoing to test whether the associations between regional tau burden and cognitive scores map onto established brain‐behavior relationships.