4 DATA ANALYSES
Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) calculates the Z score that is a value indicating the atrophic degree of the medial temporal lobe. The Z scores at the time of the intervention with the chronobiological therapy were 1.48 to 5.7 and the average was 3.085. The Z scores after the intervention were 0.93 to 5.58 and the average was 2.727 (Figure 1). The atrophic degrees of the medial temporal lobe were improved. The MMSE scores at the time of the intervention with the chronobiological therapy were 11 to 25 and the average was 16.2. The MMSE scores after the intervention were 10 to 29 and the average was 18.5 (Figure 2). Regarding Case 4 and 5, the severities of Neuropsychiatric Inventory-Questionnaire (NPI-Q) at the time of the intervention with the chronobiological therapy were 20 and 21, and the average was 20.5. The severities of NPI-Q after the intervention were 9 and 2, the average was 5.5 (Figure 3). These cases’ BPSD (Behavioral and Psychological Symptoms of Dementia) was improved.
The VSRAD Z-scores at the time of the intervention with the chronobiological therapy were from 1.48 to 5.7, and the MMSE scores were from 11 to 25 points. This Pearson correlation coefficient was -0.353, and they showed weak negative correlation (Figure 4). The Z-scores after the intervention were from 0.93 to 5.58, and the MMSE scores were from 10 to 29 points. This Pearson correlation coefficient was -0.549, and they showed negative correlation (Figure 5).
The Z scores at the time of the intervention with chronobiological therapy were 1.48 to 5.7, and the Z scores after the intervention were 0.93 to 5.58. As for the Z-scores at the time of and after the intervention, the Pearson correlation coefficient was 0.965, they showed strong positive correlation, and the irrelevant value was not seen (Figure 6). The MMSE scores at the time of the intervention with chronobiological therapy were 11 to 25, and the MMSE score after the intervention were 10 to 29. As for MMSE scores at the time of and after the intervention, the Pearson correlation coefficient of was 0.843, they showed strong positive correlation, and the irrelevant value was not seen. (Figure 7)
We achieved the recovered 0.03 to 1.28 points of VSRAD Z-score. The Pearson correlation coefficient between these recovered points and the MMSE scores at the time of the intervention was 0.872, and they demonstrated strong positive correlation (Figure 8). The Pearson correlation coefficient between these recovered points and the MMSE scores after the intervention was 0.740, and they demonstrated strong positive correlation (Figure 9).
In the chronobiological therapy, 15mg of lansoprazole and diuretics was chosen as the drug to promote awakening and activity in the morning. 20mg of furosemide or 25 mg of spironolactone was prescribed for urination in the morning in Case 4. 4.5mg of rivastigmine was prescribed to make an awakening and activity in Case 6. 80mg of valsartan, which was one of angiotensin II receptor blockers (ARBs), was mainly used for adjustment of the blood pressure. 0.125 to 0.5 mg of Clonazepam and 2.5mg of nitrazepam were selected to close an awakening and activity and stabilize sleep without REM (rapid eye movement sleep) behavior disorder (Table 1).
Japanese Kampo medicines (JKMs) were prescribed for start and closure of activities, and reconstructed awakening-sleep rhythm. 6g of Ninjin-Yoei-To, 1.25g of Toki-Syakuyaku-San, 2.5g of Hochu-Ekki-To, 7.5g of Bohu-Tsusho-San, 5 to 7.5g of Yokkan-San, 2.5 to 7.5g of Yokkan-San-Ka-Chinpi-Hange, 5g of Keishi-Ka-Shakuyaku-To, 5 to 7.5g of Oren-Gedoku-To, and 5 to 7,5g of Choto-San were used.In all cases, we used Japanese Kampo medicines including Toki, Japanese Angelica Root, and Chotoko, Uncaria Hook. 1 to 4g of Japanese Angelica Root was used, and 1 to 3g of Uncaria Hook was used (Table 2 and 3).