Development, Validation and Field Evaluation of the Singapore Longitudinal Ageing Study (SLAS) Risk Index for Prediction of Mild Cognitive Impairment and Dementia.

BACKGROUND: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. OBJECTIVE: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. DESIGN: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. SETTING: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. MEASUREMENTS: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. RESULTS: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). CONCLUSIONS: The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.

The effect of APOE genotype on brain levels of oxysterols in young and old human APOE epsilon2, epsilon3 and epsilon4 knock-in mice.

Despite apolipoprotein E's important role in cholesterol transport and metabolism in the brain as well as its influence on Alzheimer's disease, the impact of the human APOE genotype on cholesterol metabolism in brain has not been fully examined. This study was carried out to investigate APOE genotype effects on oxysterols measured. In this study the measurement of cholesterol and several oxysterols in the brains of human APOE epsilon2, epsilon3 and epsilon4 knock-in mice at 8 weeks and 1 year of age using gas chromatography mass spectrometry (GC-MS) demonstrated no APOE genotype or age effect on total brain cholesterol and the oxysterol 24-hydroxycholesterol. The level of 27-hydroxycholesterol was elevated in 1 year old animals for all APOE genotypes. Interestingly, lathosterol an indicator of cholesterol synthesis was significantly reduced in the 1 year old animals for all APOE genotypes. APOE epsilon4 expressing mice exhibited statistically lower levels of lathosterol compared to APOE epsilon2 in both the young and old mice. Oxidized cholesterol metabolites were significantly lower in APOE epsilon2 mice compared to other genotypes at 8 weeks old. Although minimal differences were observed between APOE E3 and E4 knock-in (KI) mice, these findings indicate that there are some clear APOE genotype specific effects on brain cholesterol synthesis and associated metabolic pathways, particularly in APOE epsilon2 KI mice.

The 'Rastelli' operation--results at the Singapore General Hospital.

Reconstruction of the right ventricular outflow tract in patients with right ventricle-pulmonary artery discontinuity with a valved conduit is well established. The aim of this study was to review our results at the Singapore General Hospital. Between October 1989 and May 1993, 13 patients underwent the 'Rastelli' operation. The mean age at definitive repair was 68 months. Ten patients had pulmonary atresia with ventricular septal defect, two patients truncus arteriosus (one patient each with type 3 and type 2) and one patient had tetralogy of Fallot with absent pulmonary valve syndrome. In 12 patients cryo-preserved pulmonary artery homografts with a mean diameter of 21mm (19-23mm) were used, and a 11mm composite Hancock dacron valved conduit in one patient. There were no operative deaths. The mean duration of follow-up is 37 months (23-48 months). All patients were well and in NYHA class I on recent follow-up. On echocardiographic assessment 12 patients had trivial or no gradient across the right ventricular outflow tract, while one patient had a gradient of 25mmHg. The "Rastelli" operation can be undertaken with low mortality and morbidity and early results are encouraging.

Non-surgical closure of patent ductus arteriosus with the Rashkind PDA occluder system.

Transcatheter closure of Patent Ductus Arteriosus (PDA) was done in 18 children using the USCI Rashkind PDA occluder system. Patient age ranged from 1.2 to 14 years and their weights ranged from 8 to 36 kg. Isolated restrictive PDA was present in 15 patients; 3 had additional cardiac defects. The diameter of the PDA ranged from 2 to 6 mm as determined by lateral aortogram. PDA occlusion was successfully done in all 18 children. Ten 12 mm and eight 17 mm occluders were implanted with no complications. Post-implant aortogram showed complete ductal closure in 6 and trivial or small residual ductal flow in 12 cases. Doppler color flow mapping done within 3 days of the procedure showed complete ductal closure in 9, 8 had trivial ductal flow and 1 had small ductal flow. Transcatheter technique using a Rashkind PDA occluder system is a safe and effective method of non-surgical PDA occlusion.

Balloon atrial septostomy under two dimensional echocardiographic visualisation.

From May 1988 to January 1989, we performed balloon atrial septostomy under Two Dimensional Echocardiographic visualisation on 8 patients at the bedside in the intensive care unit, in the Singapore General Hospital. Their ages ranged from 3 to 45 days (median = 7 days). Their weights ranged from 1.6 to 4.0 kg (mean +/- 2sd = 3.2 + 1.6). Five patients had transposition of the great arteries, 1 had tricuspid atresia and 2 with pulmonary atresia/stenosis. There were no complications related to the procedure. The advantage of Two Dimensional Echocardiographic imaging compared to fluoroscopy are 1) excellent visualisation of cardiac structures, 2) it can be performed safely at the bedside without transporting patient to the cardiac catheter laboratory, 3) Immediate detection of cardiac complications and 4) no radiation exposure. Balloon atrial septostomy done using Two Dimensional Echocardiographic visualisation is acceptable and safe. It is the method of choice in our department.

Percutaneous balloon pulmonary valvuloplasty--the Singapore General Hospital experience.

Percutaneous balloon pulmonary valvuloplasty was performed in ten children aged 4 months to 9 years (mean age = 3.9 years). Their weights ranged from 5.6 to 38 kg (mean = 16.1 kg). Seven had typical pulmonary valve stenosis, two had pulmonary atresia and previous surgical valvotomy and one had dysplastic pulmonary valve. In patients with typical pulmonary valve stenosis, significant reductions in the right ventricular systolic pressure and pulmonary systolic pressure gradients were observed immediately after balloon dilatation. Follow-up evaluation by Doppler echocardiography at six months to two years showed further reduction in pulmonary gradients in five, and in the other two, the gradients remained low. Reduction in right ventricular pressure was less in patients with pulmonary atresia and previous surgical valvotomy and patients with dysplastic pulmonary valve. Balloon pulmonary valvuloplasty is a safe and effective procedure for the relief of typical pulmonary valve stenosis. In patients with pulmonary atresia and previous surgical valvotomy, balloon valvuloplasty can be an effective palliation for decompressing the right ventricle and improving pulmonary blood flow.

Kawasaki disease--the Singapore experience.

50 children with Kawasaki disease were seen between September 1983 to March 1988. Their ages ranged from 3 months to 10 years with a mean age of 25 months. Male to Female ratio was 2.3 to 1. The diagnosis of Kawasaki disease was made between the fourth to fifteenth day of illness. Marked thrombocytosis, raised erythrocyte sedimentation rate, leucocytosis, mild anemia and sterile pyuria were common features. All patients had a normal ECG and chest X-ray. 2D echocardiogram was done in the sub-acute phase of the illness in every patient. Sixteen patients (32%) had coronary artery dilatation. Thirteen of these had serial 2D echocardiograms done over a period of more than one year. Twelve had echocardiographic resolution of the coronary lesion within 18 months of follow up. Patients with coronary artery dilatation were significantly younger. All had full clinical recovery with aspirin therapy. Kawasaki disease afflicts mostly young children and can present as a diagnostic problem. Coronary artery involvement is common, and except for age, it is not predictable by any clinical or laboratory parameter. Serial echocardiographic examinations are necessary in the management of these patients.

Efficacy of verapamil in the conversion of supraventricular tachycardia in Singapore children.

The efficacy of verapamil in the conversion of 47 episodes of supraventricular tachycardia in 22 children was evaluated. The age of the patients ranged from 15 days to 10 years. Tachycardia was the main mode of presentation. Ten out of 22 children had viral infections. Two patients developed mild cardiac failure. Six patients had underlying cardiac abnormalities. Forty-four out of 47 episodes of supraventricular tachycardia were converted to sinus rhythm by a single dose of verapamil (0.11 +/- 0.08 mg/kg). No significant side-effects were observed. Intravenous verapamil is an effective and safe drug for the conversion of supraventricular tachycardia in children.