Effect of CYP2D6 and CYP3A4 Genotypes on the Efficacy of Cholinesterase Inhibitors in Southern Chinese Patients With Alzheimer's Disease.

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.

Continuous use of antipsychotics and its association with mortality and hospitalization in institutionalized Chinese older adults: an 18-month prospective cohort study.

BACKGROUND: Previous meta-analyses have suggested that antipsychotics are associated with increased mortality in dementia patients with behavioral and psychological symptoms (BPSD). Subsequent observational studies, however, have produced conflicting results. In view of this controversy and the lack of any suitable pharmacological alternative for BPSD, this study aimed to investigate the relationship between continuous use of antipsychotics and mortality as well as hospitalizations in Chinese older adults with BPSD residing in nursing homes. METHODS: This was a prospective cohort study conducted in nursing homes in the Central & Western and Southern Districts of Hong Kong from July 2009 to December 2010. Older adults were stratified into the exposed group (current users of antipsychotics) and control group (non-users). Demographics, comorbidity according to the Charlson Comorbidity Index (CCI), Barthel Index (BI(20)), Abbreviated Mental Test (AMT), and vaccination status for pandemic Influenza A (H1N1) 2009, seasonal influenza and pneumococcus were collected at baseline. Subjects were followed up at 18 months. All-cause mortality and all-cause hospitalizations were recorded. RESULTS: 599 older adults with dementia from nine nursing homes were recruited. The 18-month mortality rate for the exposed group was 24.1% while that for control group was 27.5% (P = 0.38). The exposed group also had a lower median rate of hospitalizations (56 (0-111) per 1000 person-months vs 111 (0-222) per 1000 person-months, median (interquartile range), p<0.001). CONCLUSIONS: The continuous use of antipsychotics for BPSD does not increase mortality among Chinese older adults with dementia living in nursing homes. Furthermore, our results show that the use of antipsychotics can lead to decreased hospitalizations.

The geriatric depression scale as a screening tool for depression and suicide ideation: a replication and extention.

OBJECTIVES: To examine a) whether the Geriatric Depression Scale (GDS) can predict clinician-rated suicide ideation and depression, using the 15-, 5-, and 4-item versions, b) whether an additional suicide-ideation item would improve the performance, and c) whether the results vary by age groups. METHODS: First-time psychiatric outpatients responded to the GDS. They were subsequently assessed by psychiatrists blind to the GDS, who also indicated whether suicide ideation was present. The performance of the GDS scales was evaluated using receiver operating characteristic curves. Analyses were conducted separately for young-old (aged 60-74 years) and old-old (aged 75 years or older) adults. RESULTS: Areas under the curves showed that the different GDS versions were comparable in detecting depression and suicide ideation. For identifying depression, thresholds of 7, 2, and 2 for the 15-, 5-, and 4-item versions were optimal, respectively. In terms of detecting suicide ideation, all measures performed better in old-old than in young-old adults. A single, self-report suicide-ideation item performed better than all multiitem GDS measures. CONCLUSIONS: Both the 4- and the 5-item versions are excellent alternatives to the 15-item version, and all are reasonable tools for detecting the presence of suicide ideation also. However, to improve the effectiveness of screening, brief measures of suicide risk should also be included. Even a 1-item measure of suicide ideation can improve clinical decisions tremendously.