Synaptic density, tau and multiparametric PET-MR for quantitative functional assessment and prognosis in mild cognitive and behavioural impairment

With annually 9.9 million new cases worldwide and as one of the

costliest diseases, the impact of dementia cannot be underestimated.

Although research in this domain has made significant progress,

major challenges still lie ahead. There is a growing need of

biomarkers with the capacity to diagnose Alzheimer’s disease (AD) in

an early stage, predict prognosis for prodromal patients and monitor

treatment. To date, there are no such biomarkers available. PET-MR

imaging of tau protein and synaptic density (SD), which only recently

became possible through the development of radiotracers 18F-MK-

6240 and 11C-UCB-J, could provide an answer to this need. The

deposition of Tau and the loss of SD are two related pathological

hallmarks of AD that change early in the disease course. We

hypothesize that in patients with mild cognitive or behavioral

impairment, prodromal presentations of AD, the uptake of 18F-MK-

6240 is increased in the medial temporal cortex, related to cognitive

or behavioral changes. Accompanying this, we expect a decrease in

SD, measured by 11C-UCB-J, diminished network connectivity and

decrease in white matter organization. These changes will deteriorate

over the course of 2 years in patients that evolve to AD. The objective

of this project is to determine the added value and potential clinical

implementation of Tau and SD simultaneous PET-MR imaging in

prodromal AD, which will be accomplished in a longitudinal design

from early symptom onset to 2 years of follow up