METHODS: Using indirect calorimetry, REE was measured at acute (≤5 days; n = 294) and late (≥6 days; n = 180) phases of intensive care unit admission. PEs were developed by multiple linear regression. A multi-fold cross-validation approach was used to validate the PEs. The best PEs were selected based on the highest coefficient of determination (R2), the lowest root mean square error (RMSE) and the lowest standard error of estimate (SEE). Two PEs developed from paired 168-patient data were compared with measured REE using mean absolute percentage difference.
RESULTS: Mean absolute percentage difference between predicted and measured REE was <20%, which is not clinically significant. Thus, a single PE was developed and validated from data of the larger sample size measured in the acute phase. The best PE for REE (kcal/day) was 891.6(Height) + 9.0(Weight) + 39.7(Minute Ventilation)-5.6(Age) - 354, with R2 = 0.442, RMSE = 348.3, SEE = 325.6 and mean absolute percentage difference with measured REE was: 15.1 ± 14.2% [acute], 15.0 ± 13.1% [late].
CONCLUSIONS: Separate PEs for acute and late phases may not be necessary. Thus, we have developed and validated a PE from acute phase data and demonstrated that it can provide optimal estimates of REE for patients in both acute and late phases.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03319329.
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).
CONCLUSION: We recommend a reliable method in measuring the brain atrophy and locating the patterns of hypometabolism using a group-specific template registered to a quantitatively validated KNE96 group-specific template. The studied regions together with neuropsychological test approach is an effective method for the determination of AD severity in a Malaysian population.