Tandem 10: Imaging Brain Beta-Amyloid in Patients with Mild Cognitive Impairment (MCI) and Beginning Alzheimer’s Disease (AD)

Short Summary:

We investigate the change of brain beta-amyloid over time and its impact on cognitive performance in patients with mild cognitive impairment and beginning Alzheimer’s disease. Furthermore, we determine whether brain beta-amyloidosis is associated with MRI signs of brain atrophy and FDG PET signs of altered brain function.

Scope:

This project is designed to explore the value of “PiB” PET-imaging of brain beta-amyloid in the early detection of cognitive impairment and dementia. Groundbreaking work of investigators at the University of Pittsburgh lead to the development of a Thioflavin-T derivative that penetrates the blood brain barrier very well and binds to brain amyloid with high affinity (Klunk et al., 2004); the compound Nmethyl [11C]2-(4’-methylaminophenyl)-6-hydroxybenzothiazole, was nicknamed “PiB” for Pittsburgh Compound B. PiB binds specifically to extracellular and intravascular fibrillar beta-amyloid deposits in post mortem AD brains. At PET tracer concentrations, PiB shows a high sensitivity in identifying AD, diagnostic specificity, however, is not yet fully determined due to the fact that a relevant portion of cognitively normal elderly subjects display brain beta-amyloid deposition (for review see: (Rabinovici and Jagust, 2009)). It has been consistently shown that elevated PiB-binding in subjects with MCI increases the risk of converting to full blown AD within a few years (Forsberg et al., 2008). Here we plan to use PiB to assess brain beta-amyloid load in patients with (MCI) as defined according to (Winblad et al., 2004) and beginning AD (according to (McKhann et al., 2011)). Towards this aim 100 subjects with MCI and 100 subjects with beginning dementia syndromes will be included and submitted to annual cognitive testing and MR imaging, along with biannual PiB PET scanning. The present study will reveal the potential of PiB imaging in early detection of Alzheimer’s disease and establish its role as a clinical tool for early diagnosis and therapeutic monitoring.

Specific Aims:

1) To explore the impact of brain beta-amyloid on cognitive performance and change over time in mild cognitive impairment (MCI) and beginning Alzheimer’s disease (AD). 2) To determine whether brain beta-amyloidosis is associated with MRI signs of brain atrophy and FDG PET signs of altered brain function.

Molecular imaging techniques used:

N-methyl [11C]2-(4’methylaminophenyl)-6-hydroxybenzothiazole, “PiB” for Pittsburgh Compound B (PiB) (Klunk et al., 2004); FDG-PET.

Zoom (JPG, 112 KB)
Overlays of amyloid-scan (11C-PiB) and MR in Patients with mild cognitive impairment. White matter signal of corpus callosum was set as lower threshold. Red and yellow colors indicate high specific binding of 11-C-PiB to fibrillar Aβ-deposits, which indicate a higher risk of progression to Alzheimer’s disease. Subject on the right also displays significant hippocampal atrophy another important biomarker of prodromal Alzheimer’s disease.

Added value of KFSP for this specific tandem project:

Translational research project; this study will establish PiB imaging as the prime clinical tool to identify subjects at risk for dementia or beginning disease allowing for clinical testing of preventive strategies and early therapeutic intervention.

References