18FTHK5351 PET Imaging in Patients with Mild Cognitive Impairment

Background@#and PurposeMild 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.

¹⁸F-THK5351 PET Imaging in Nonfluent-Agrammatic Variant Primary Progressive Aphasia

BACKGROUND AND PURPOSE: To analyze 18F-THK5351 positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). METHODS: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, 18F-THK5351 PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of 18F-THK5351 in navPPA patients. RESULTS: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. CONCLUSIONS: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.

Effect of Goreisan on Diarrhea Model Mouse Induced by Saline Purgative / 日本東洋医学雑誌

Goreisan, a well-known hydrostatic modulating formulation, is used clinically in the treatment of edematous disorders. In this study, in order to clarify hydrostatic modulation in the intestine, we analyzed the effect of Goreisan in an experimental diarrhea model created with the single oral pretreatment of magnesium sulfate in mice. Ninjinto (166mg/kg, p.o.) did not lead to improvements in this model, whereas Goreisan (133mg/kg, p.o.) significantly abated the diarrhea.The warm Goreisan extraction (at 37°C, for 0.5hr) showed anti-diarrheal activity that was significantly stronger than the decoction. On investigating the anti-diarrheal activity of Goreisan by comparing the difference in crude drugs made from Atractylodis Rhizoma (Byakujutsu) and Atractylodis Lanceae Rhizoma (Sojutsu), no distinction between Byakujutsu-Goreisan and Sojutsu-Goreisan was recognized. Atractylodis Rhizoma, Polyporus, Poria, and Cinnamomi Cortex, which were administered singly, showed anti-diarrheal activities, but these were weak in comparison with Goreisan. Concoctions in which either Atractylodis Rhizoma, Polyporus, Poria, Alismatis Rhizoma, or Cinnamomi Cortex were omitted from Goreisan showed decreased anti-diarrheal activity as compared with Goreisan. The anti-diarrheal activity was clearly lower in the concoctions of warm extractions whereby the five kinds of crude drugs were extracted separately, compared with the warm extraction of Goreisan in which all crude drugs were extracted simultaneously.These findings suggest that the anti-diarrheal activity of Goreisan in this model was not dependent on a specific crude drug, it being optimal to extract the five kinds of crude drug simultaneously.