[(18)F]FDG, [(11)C]PiB, and [(18)F]AV-1451 PET Imaging of Neurodegeneration in Two Subjects With a History of Repetitive Trauma and Cognitive Decline

Background: Trauma-related neurodegeneration can be difficult to differentiate from multifactorial neurodegenerative syndromes, both clinically and radiographically. We have initiated a protocol for in vivo imaging of patients with suspected TBI-related neurodegeneration utilizing volumetric MRI and PET studies, including [(18)F]FDG indexing cerebral glucose metabolism, [(11)C]PiB for Aβ deposition, and [(18)F]AV-1451 for tau deposition. Objective: To present results from a neuroimaging protocol for in vivo evaluation of TBI-related neurodegeneration in patients with early-onset cognitive decline and a history of TBI. Methods: Patients were enrolled in parallel TBI studies and underwent a comprehensive neuropsychological test battery as well as an imaging protocol of volumetric MRI and PET studies. Findings from two patients were compared with two age-matched control subjects without a history of TBI. Results: Both chronic TBI patients demonstrated cognitive deficits consistent with early-onset dementia on neuropsychological testing, and one patient self-reported a diagnosis of probable early-onset AD. Imaging studies demonstrated significant [(18)F]AV-1451 uptake in the bilateral occipital lobes, substantial [(11)C]PiB uptake throughout the cortex in both TBI patients, and abnormally decreased [(18)F]FDG uptake in the posterior temporoparietal areas of the brain. One TBI patient also had subcortical volume loss. Control subjects demonstrated no appreciable [(18)F]AV-1451 or [(11)C]PiB uptake, had normal cortical volumes, and had normal cognition profiles on neuropsychological testing. Conclusions: In the two patients presented, the [(11)C]PiB and [(18)F]FDG PET scans demonstrate uptake patterns characteristic of AD. [(11)C]PiB PET scans showed widespread neocortical uptake with less abnormal uptake in the occipital lobes, whereas there was significant [(18)F]AV-1451 uptake in both occipital lobes.