The Effect of Choline Acetyltransferase Genotype on Donepezil Treatment Response in Patients with Alzheimer's Disease

OBJECTIVE: We examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans. METHODS: Patients who met the criteria for probable Alzheimer's disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student's t-test. RESULTS: At 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively). CONCLUSION: Our findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans.

Effects of administration of IH901, a ginsenoside intestinal metabolite, on muscular and pulmonary antioxidant functions after eccentric exercise

This study was conducted to investigate whether administration of IH901, a ginseng intestinal metabolite, ameliorates exercise-induced oxidative stress while preserving antioxidant defense capability in rat skeletal muscles and lung. Eight adult male Sprague-Dawley rats per group were randomly assigned to the resting control, exercise control, resting with IH901 (25, 50, and 100 mg/kg) consumption (R/IH901), or exercise with IH901 (25, 50, and 100 mg/kg) consumption (E/IH901) group. The trained groups ran 35 min 2 days/week for 8 weeks. To analyze the IH901-training interaction, serum biochemical analysis, lipid peroxidation, citrate synthase, protein oxidation, antioxidant and superoxide dismutase in skeletal muscles and lung tissue were measured. Compared to the exercise control group, animals that consumed IH901 had significantly increased exercise endurance times (p < 0.05) and decreased plasma creatine kinase and lactate dehydrogenase levels (p < 0.05), while those in the E/IH901 groups had increased citrate synthase and anti-oxidant enzymes and decreased lipid peroxidation and protein oxidation (p < 0.05). In conclusion, IH901 consumption in aging rats after eccentric exercise has beneficial effects on anti-inflammatory and anti-oxidant activities through down-regulation of pro-inflammatory mediators, lipid peroxidation, and protein oxidation and up-regulation of anti-oxidant enzymes.

In vitro antioxidant properties of a ginseng intestinal metabolite IH-901 / 한국실험동물학회지

IH-901 (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol or compound K) is a final intestinal bacterial metabolite of ginseng in humans. It has various pharmacologic effects such as antiaging, immunopotentiation, antistress, and antimetastatic activities. We analyzed the antioxidant activities of IH-901 using several assays including: total antioxidant activity, reductive potential, 1,1-diphenyl-2-picryl-hydrazyl, hydroxyl, superoxide and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, a nitric oxide scavenging assay and a lipid peroxidation assay. At concentrations of 25 and 100 microg/mL, IH-901 inhibited lipid peroxidation of a linoleic acid emulsion with a potency comparable to ascorbic acid and butylated hydroxyanisole. The reductive potential of IH-901 increased in a concentration-dependent manner. IH-901 exhibited strong DPPH, hydroxyl, superoxide and ABTS radical scavenging activities. IH-901 was also an effective inhibitor of lipid peroxidation, although IH-901 had only a mild scavenging activity against nitric oxide. These results suggest that IH-901 may be a useful antioxidant agent against reactive oxygen species.

Effect of Galantamine on Caregiver Time and Activities of Daily Living in Mild to Moderate Alzheimer's Disease: A 1-Year Prospective Study

OBJECTIVE: This study aims to investigate the effect of galantamine on caregiver time and activities of daily living(ADLs) in patients with mild to moderate Alzheimer's disease(AD) in a Korean population. DESIGN: Quasi-experimental study: A rndomized, double-blind, parallel-group clinical trial and a naturalistic longitudinal community study METHOD: For this 1-year prospective study, 138 patients residing in the community were recruited(baseline MMSE score of. 10-22). The two groups were composed of 72 patients treated with galantamine and 66 patients selected as the control group from an untreated community cohort of AD patients. The primary efficacy outcome was the caregiver time and the secondary efficacy measure was the Korean version of the Disability Assessment for Dementia(DAD-K) scale. RESULTS: The results of a mixed model analyses demonstrated reduced caregiver time and improved ADLs in galantamine group relative to baseline and compared with the community control group in this 1-year prospective study. Significant improvement in galantamine group observed in the DAD scores demonstrated beneficial effects of galantamine on delaying functional deterioration in patients with mild to moderate AD. Difference in caregiver time between two groups was equivalent to additional 9.5 working days per month or 113 working days per year. CONCLUSION: Treatment with Galantamine is associated with a significantly slower decline in basic and instrumental ADLs in patients with mild to moderated AD. These benefits on functional capacity in patients with AD treated with galantamine were associated with less caregiver time, lower caregiver burden and higher economic benefits.