ABSTRACT
Alzheimer's disease (AD) is the most prevalent form of dementia, and age is strongly associated with the incidence of AD. This study aimed to investigate the association between the genotypes of CYP2D6, CYP3A4, and CYP2C9 genes to the clinical efficacy and tolerability of cholinesterase inhibitors (ChEIs) in Chinese patients with AD. One hundred seventy-nine patients with AD with newly prescribed with ChEIs were recruited. The clinical response and tolerability were evaluated at baseline, 3rd-, 6th-, and 12th-month follow-ups and were compared according to their genotypes of CYP2D6, CYP3A4, and CYP2C9. Among patients prescribed with donepezil/galantamine, CYP2D6*10 carriers showed significantly less side effects (P = .009). CYP2D6*10 carriers responded better to ChEIs and resulted in better improvement in Alzheimer's Disease Assessment Scale-Cognitive subscale (P = .027) and Mini-Mental State Examination (P = .012). Further study is required to replicate the finding, and it might be useful for clinicians to decide the medication based on the patients' CYP genotypes.
Subject(s)
Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/pharmacology , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP3A/genetics , Donepezil/pharmacology , Pharmacogenetics , Aged , Aged, 80 and over , Cholinesterase Inhibitors/adverse effects , Cytochrome P-450 CYP2C9/genetics , Donepezil/adverse effects , Female , Follow-Up Studies , Galantamine/pharmacology , Genotype , Hong Kong , Humans , Male , Pharmacogenomic Testing , Rivastigmine/pharmacologyABSTRACT
OBJECTIVE: To investigate the beneficial effect of constraint-induced movement therapy in improving the function of hemiplegic upper extremity in the early subacute stroke patients. DESIGN: A prospective, single-blinded, randomized controlled study comparing the effectiveness of constraint-induced movement therapy or control treatment at post intervention and 12 weeks follow-up. SUBJECTS: The inclusion criteria were 2-16 weeks after stroke, hemiparesis of the affected limb, minimal function of > or =20 degrees wrist extension and > or =10 degrees extension of all digits and Mini-Mental State Examination score > or =17. INTERVENTIONS: The intervention group underwent a programme of 10 days upper extremity training (4 hours per day) with the unaffected limb being restrained ina shoulder sling and the control group received an equivalent duration of conventional rehabilitation therapy. MAIN MEASURES: Functional level for hemiparetic upper extremity, Motor Activity Log, Action Research Arm Test and modified Barthel Index. RESULTS: There were 23 and 20 subjects respectively in the constraint-induced movement therapy and control groups. Significant improvements were seen at post intervention and 12 weeks after constraint-induced movement therapy in functional level for hemiparetic upper extremity (P= 0.001), and in the ;amount of use' (P= 0.001) and ;how well' (P= 0.021) subscales of the Motor Activity Log. The total Action Research Arm Test score, grasp (P= 0.004), grip (P= 0.004), pinch (P= 0.032) and gross (P= 0.006) components showed significant improvement over the control group at post intervention. The grip component (P=0.019) and the total Action Research Arm Test score (P= 0.009) were superior to the control group at 12 weeks. CONCLUSION: Significant improvement in hand function could be achieved with constraint-induced movement therapy in subacute stroke patients, which was maintained up to 12 week follow-up.
