ABSTRACT
There was no long-term clinical study on galantamine in Alzheimer's disease (AD) in the Asian population. The objectives of this study were to evaluate the efficacy of galantamine on cognitive function, daily functioning, behavioural symptoms and its safety in Chinese AD patients. This was a 2-year open-label clinical trial. The inclusion criteria were patients with probable AD by the NINCDS-ADRDA criteria. A historical control group (n = 19) of AD patients with no galantamine or other cholinesterase inhibitor therapy was employed. In the galantamine group, 33 and 32 subjects had completed a 1-year and 2-year follow up, respectively. Within the galantamine group and at a 6-month follow up, the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog score) showed an improvement of 2.9 +/- 1.18 (p = 0.019, paired t-test) but remained the same at 1 and 2 years. The Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) deteriorated by 4.31 +/- 2.06 (p = 0.044, paired t-test) at 6 months but showed no significant decline at 1 and 2 years vs. baseline. The Neuropsychiatric Inventory (NPI) score also showed a significant deterioration of 5 +/- 1.99 (p = 0.017, paired t-test) at 6 months, 8.06 +/- 1.97 (p < 0.001, paired t-test) at 1 year and 7.31 +/- 1.76 at 2 years. Comparison between the two groups showed a statistically significant improvement in the 1-year ADAS-cog score but decline in the NPI score in the galantamine vs. control groups. Adverse effects were commonly mild. In Chinese mild-moderate AD patients, galantamine showed beneficial effects mainly on the cognitive function.
Subject(s)
Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/therapeutic use , Galantamine/therapeutic use , Nootropic Agents/therapeutic use , Activities of Daily Living , Aged , Alzheimer Disease/ethnology , China/ethnology , Cholinesterase Inhibitors/adverse effects , Cognition/drug effects , Female , Follow-Up Studies , Galantamine/adverse effects , Hong Kong/epidemiology , Humans , Male , Neuropsychological Tests , Nootropic Agents/adverse effects , Severity of Illness Index , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Cholesterol metabolism has been implicated in the pathophysiology of Alzheimer's disease (AD), and cholesterol-related genes are plausible candidate genes for AD. Genetic association of CYP46A1 polymorphisms with AD had been under extensive investigations; however, observations on intron 2 T-->C (rs754203) generated inconclusive results. OBJECTIVE: To analyse an independent data set in a Chinese population to see whether the polymorphic site rs754203 of the CYP46A1 gene is associated with AD. METHODS: We analysed 130 sporadic AD patients and 110 healthy controls of the Southern Chinese origin. RESULTS: An association between the genotype frequency and AD was suggested in the general population (p = 0.047, odds ratio, OR = 1. 61, 95% confidence interval, CI = 0.96-2.70), while the association was most significant in the apolipoprotein E (ApoE) epsilon4-negative group (p = 0.004, OR = 2.54, 95% CI =1.31-4.95). Linkage disequilibrium block prediction results also favoured this association. Consistent with previous reports, intron 3 C-->T (rs4900442) polymorphism did not show any evidence of association; in our data set ApoEepsilon4 was confirmed to be a genetic risk factor for AD (p = 0.0016, OR = 2.76, 95% CI = 1.50-5.11).
