MATERIALS AND METHODS: 18F-FDG PET/CT images of 14 healthy control (HC) subjects (MoCA score > 26 (mean+SD~ 26.93+0.92) with no clinical evidence of cognitive deficits or neurological disease) and 16 AD patients (MoCA ≤22 (mean+SD~18.6+9.28)) were pre-processed in SPM12 while using our developed Malaysian healthy control brain template. The AD patients were assessed for disease severity using ADAS-Cog neuropsychological test. KNE96 template was used for registration-induced deformation in comparison with the ICBM templates. All deformation fields were corrected using the Malaysian healthy control template. The images were then nonlinearly modified by DARTEL to segment grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) to produce group-specific templates. Age, intracranial volume, MoCA score, and ADASCog score were used as variables in two sample t test between groups. The inference of our brain analysis was based on a corrected threshold of p<0.001 using Z-score threshold of 2.0, with a positive value above it as hypometabolic. The relationship between regional atrophy in GM and WM atrophy were analysed by comparing the means of cortical thinning between normal control and three AD stages in 15 clusters of ROI based on Z-score less than 2.0 as atrophied.

RESULTS: One-way ANOVA indicated that the means were equal for TIV, F(2,11) = 1.310, p=0.309, GMV, F(2,11) = 0.923, p=0.426, WMV, F(2,11) = 0.158, p=0.856 and CSF, F(2,11) = 1.495 p=0.266. Pearson correlations of GM, WM and CSF volume between HC and AD groups indicated the presence of brain atrophy in GM (p=-0.610, p<0.0001), WM (p=-0.178, p=0.034) and TIV (p=-0.374, p=0.042) but showed increased CSF volume (p=0.602, p<0.0001). Voxels analysis of the 18FFDG PET template revealed that GM atrophy differs significantly between healthy control and AD (p<0.0001). Zscore comparisons in the region of GM & WM were shown to distinguish AD patients from healthy controls at the prefrontal cortex and parahippocampal gyrus. The atrophy rate within each ROI is significantly different between groups (c2=35.9021, df=3, p<0.0001), Wilcoxon method test showed statistically significant differences were observed between Moderate vs. Mild AD (p<0.0001), Moderate AD vs. healthy control (p=0.0005), Mild AD vs. HC (p=0.0372) and Severe AD vs. Moderate AD (p<0.0001). The highest atrophy rate within each ROI between the median values ranked as follows severe AD vs. HC (p<0.0001) > mild AD vs. HC (p=0.0091) > severe AD vs. moderate AD (p=0.0143).

MATERIALS AND METHODS: This study was conducted at Department of Anatomy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada starting on July 20th, 2020. A total of 24 male Wistar rats were randomly divided into six groups (four rats per group), i.e., control, DM 1.5 months (DM1.5), and DM 2 months (DM2); and DM groups treated with CGA in three different doses, namely CGA1 (12.5 mg/kg BW), CGA2 (25 mg/kg BW), and CGA3 (50 mg/kg BW). Control group was only injected with normal saline, while diabetic model was induced by intraperitoneal injection of streptozotocin. Blood glucose levels were measured twice (one week after diabetic induction and before termination). The soleus muscle tissue was harvested to analyse the mRNA expressions of SOD-1, SOD- 2, CN and PGC-1α using RT-PCR. In addition, the tissue samples were stained with immunohistochemistry for CN and haematoxylin-eosin (HE) for morphologic analysis under light microscopy.

RESULTS: The mRNA expressions of SOD-1 and SOD-2 in the CGA1 group were relatively higher compared to the DM2 groups. The mRNA expression of CN in the CGA1 group was significantly higher compared to the DM2 group (p = 0.008). The mRNA expression of PGC-1α in the CGA1 group was significantly higher compared to the DM2 group (p = 0.025). Immunohistochemical staining showed that CNimmunopositive expression in the CGA1 group was more evident compared to the other groups. Haematoxylin-eosin staining showed that muscle tissue morphology in the CGA1 group was similar to that in the control group.