[¹⁸F]THK5351 PET imaging in patients with mild cognitive impairment

Background and Purpose Mild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [¹⁸F]THK5351 in MCI subgroups. Methods This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [¹⁸F]THK5351 PET, and detailed neuropsychological tests. [¹⁸F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [¹⁸F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [¹⁸F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. Results [¹⁸F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [¹⁸F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [¹⁸F]THK5351 retention. Conclusions [¹⁸F]THK5351 PET might be useful for identifying distinct topographic patterns of [¹⁸F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer’s dementia.