Apolipoprotein E Gene Revisited: Contribution of Rare Variants to Alzheimer's Disease Susceptibility in Southern Chinese.

BACKGROUND: APOE ε4 is the best-known risk factor for late-onset alzheimer's disease (AD). Population studies have demonstrated a relatively low prevalence of APOE ε4 among Chinese population, implying additional risk factors that are Chinese-specific may exist. Apart from - alleles, genetic variation profile along the full-length APOE has rarely been investigated. OBJECTIVE: In this study, we filled this gap by comprehensively determining all genetic variations in APOE and investigated their potential associations with late-onset AD and mild cognitive impairment (MCI) in southern Chinese. METHODS: Two hundred and fifty-seven southern Chinese participants were recruited, of whom 69 were AD patients, 83 had MCI, and 105 were normal controls. Full-length APOE from promoter to 3'UTR regions were sequenced. Genetic variants were identified and compared among the three groups. RESULTS: While APOE ε4 was more significantly found in AD patients, the prevalence of APOE ε4 in southern Chinese AD patients was the lowest when compared to other areas of China and nearby regions, as well as other countries worldwide. We further identified 13 rare non-singleton variants in APOE. Significantly more AD patients carried any of the rare non-singleton variants than MCI and normal subjects. Such difference was observed in the non-carriers of ε4-allele only. Among the identified rare variants, the potential functional impact was predicted for rs532314089, rs553874843, rs533904656 and rs370594287. CONCLUSION: Our study suggests an ethnic difference in genetic risk composition of AD in southern Chinese. Rare variants on APOE are a potential candidate for AD risk stratification biomarker in addition to APOE-ε4.

Neuropsychological Profile and Dementia Symptom Recognition in Help-Seekers in a Community Early-Detection Program in Hong Kong.

OBJECTIVES: To examine the neuropsychological and clinical profile of help-seekers in an early-detection community dementia program and to explore any relationship between profiles and time to seek help. DESIGN: Cross-sectional. SETTING: Early-detection community dementia program. PARTICIPANTS: Help-seekers (N = 1,005) with subjective cognitive complaints or complaints from an informant. MEASUREMENTS: Neurocognitive testing, including the Cantonese Mini-Mental State Examination (MMSE), Clock Drawing Test, Digit Span, and Fuld Object Memory Evaluation and other clinical and functioning assessments, including the Clinical Dementia Rating (CDR), activities of daily living (ADLs), instrumental ADLs (IADLs), and depressive symptoms. Time since the person or an informant reported that they first noticed symptoms. RESULTS: Eighty-six percent of help-seekers had at least very mild dementia (CDR score ≥0.5). Cognitive performance was moderately impaired (mean MMSE score 18.4 ± 6.1). They required some assistance with IADLs, had very mild ADL impairments, and had few depressive symptoms. Median time to seek assessment was 12 months (interquartile range 7-30 months) according to the person or the informant (an adult child in 75% of the sample). Using the median-split method, time to seek assessment was classified as early (0-12 months) and late (>12 months). Worse cognitive and IADL performance but not ADL performance or depressive symptoms were observed in late than in early help-seekers. Longer time intervals between symptom recognition and early assessment showed a trend of further impairments on all measures except ADLs. CONCLUSION: A time interval of more than 12 months between symptom recognition and early assessment appears to be associated with worse cognitive function upon presentation.

Development of Six Arts, a Culturally Appropriate Multimodal Nonpharmacological Intervention in Dementia.

PURPOSE: There is accumulating evidence for the efficacy of nonpharmacological multimodal stimulation interventions in maintaining cognition and improving quality of life in people with mild-to-moderate dementia. However, the complex nature of these interventions limits their application in practice and research. We report here the design and development of a culturally appropriate framework, the Six Arts, to guide delivery of multimodal interventions in a Chinese community. DESIGN AND DEVELOPMENT: The Six Arts are a core set of Confucian philosophy comprising 6 disciplines of rites, music, archery, charioteering, literacy, and numeracy. They correspond to major mind-body functional domains of social functioning; music and rhythm; visuospatial and fine motor skills; kinesthetic and gross motor skills; language and verbal skills; and executive function. Using Six Arts as a framework, we mapped theoretical principles and evidence-based nonpharmacological interventions of cognitive stimulation, physical exercise, and social activities against the 6 functional domains. From 2011, we field-tested the use of Six Arts in structuring intervention programs in 263 people in a dementia day center in Hong Kong. RESULTS: The Six Arts was operationalized through the development of an intervention activity database, a scoring system for intensity level, and a service delivery model for application in dementia day centers. IMPLICATIONS: Six Arts can be used as framework for structuring nonpharmacological group intervention programs in dementia day center in a metropolitan Chinese city. Its cultural appropriateness may facilitate communication and shared decision making with families with dementia in communities influenced by Confucian philosophy.

A case of young-onset dementia.

Dementia is a major worldwide public health concern in view of the global ageing phenomenon. Dementia usually occurs in old age. However, if the symptoms occur in young patients, the diagnosis can be challenging. Posterior cortical atrophy is a variant of the Alzheimer's disease, which is described as a presenile disease affecting relatively late-middle-aged patients. A combination of clinical, neuropsychological, and neuroimaging techniques may facilitate making a diagnosis of this particular patient group, as demonstrated in this report. Although there is no effective disease-modifying agent for treating these patients to date, there may be considerable pressure to arrive at a quick and accurate diagnosis from the perspective of employment and insurance.

Effect of early pulmonary rehabilitation on health care utilization and health status in patients hospitalized with acute exacerbations of COPD.

BACKGROUND AND OBJECTIVE: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) incur heavy utilization of health-care resources for patients who require hospitalization. We evaluated whether an early outpatient pulmonary rehabilitation programme (PRP) after hospitalization for AECOPD could reduce acute health-care utilization over the succeeding year. METHODS: Sixty patients admitted with AECOPD were randomized to either PRP or usual care (UC). The PRP group received 8weeks of outpatient rehabilitation programme 2-3weeks after discharge from hospital. Lung function, 6min walk test and dyspnoea score were assessed at baseline, 3, 6, 9 and 12months, while St George's respiratory questionnaire and cardiopulmonary exercise test were assessed at baseline, 3, 6 and 12months. RESULTS: The PRP and UC groups demonstrated a 53.3% and 43.3% risk of readmissions at 12months (incident risk ratio 0.97 (95% CI: 0.57-1.60), P=0.90). The mean readmission rates were 1.00±1.20 and 1.03±1.87 (P=0.47) for the PRP versus UC groups respectively. The rates of AECOPD and emergency department visits were similar between the two groups. The St George's respiratory questionnaire total score was lower in the PRP group (40.15±19.10 vs 46.91±18.21, P=0.01 and 42.3±20.06 vs 51.44±18.98 P=0.01 at 3 and 6months respectively). There were no statistically significant differences in the FEV(1) % predicted, dyspnoea score, 6min walk test and maximal oxygen consumption during exercise test between PRP and UC at different time points. CONCLUSIONS: An early rehabilitation programme following AECOPD led to improvement in quality of life up to 6months, but did not reduce health-care utilization at 1year.

Tuberculin skin test reaction and body mass index in old age home residents in Hong Kong.

OBJECTIVES: To study the relationship between body mass index (BMI) and tuberculin skin test (TST) reaction in predicting the development of active tuberculosis (TB). DESIGN: A follow-up study. SETTING: Old age homes. PARTICIPANTS: Three thousand six hundred five residents who took part in a screening program for TB and had two-step TST using two units of the tuberculin PPD-RT23. MEASUREMENTS: Rate of development of active TB in these residents over an average follow-up period of 2.5+/-1.25 years. RESULTS: After one-step and two-step testing, 46.3% and 69.6% of residents, respectively, had positive TST reactions (> or =10 mm). Thirty-four residents developed active TB (323 per 100,000 person-years) during follow-up. The only significant risk factors associated with development of active TB were positive TST according to one-step testing (adjusted odds ratio (OR)=2.91, 95% confidence interval (CI)=1.26-6.74) and a BMI less than 18.5 (adjusted OR=3.15, 95% CI=1.45-6.86). Residents with a BMI less than 18.5 and a negative TST also had greater risk of active TB than residents with a BMI greater than 18.5 and negative TST (adjusted OR=4.36, 95% CI=1.04-18.3), whereas those with a positive TST had the highest risk (adjusted OR=10.2, 95% CI=2.63-39.4). Two-step testing increased the sensitivity but reduced the specificity of TST in identifying active TB on follow-up. CONCLUSION: In the elderly population, interpretation of TST should take into consideration the BMI of the individual. A positive TST according to one-step but not two-step testing was useful in predicting the development of active TB on follow-up.

Prevalence of tuberculous infection and active tuberculosis in old age homes in Hong Kong.

OBJECTIVES: To assess the prevalence of tuberculous infection and active tuberculosis (TB) in old age homes in Hong Kong and to determine whether there is institutional transmission in these homes. DESIGN: Cross-sectional. SETTING: Old age homes. PARTICIPANTS: Total of 2,243 residents, representing 84.6% of all residents in 15 old age homes; 1,698 were women, and 545 were men, with an average age of 82. MEASUREMENTS: All residents had a questionnaire-based interview, medical record review, two-stage tuberculin testing using two units purified protein derivative-RT23, and a chest x-ray. Those with radiological abnormalities had sputum examined for acid-fast bacilli. RESULTS: The estimated prevalence rate of active TB in this population was 669 per 100,000, significantly higher in men than in women (1,101 per 100,000 vs 530 per 100,000). The proportion with positive tuberculin reactivity (> or =10 mm induration) after two-stage testing was 68.6%, significantly higher in men than in women. There was no evidence of active transmission of disease in these old age homes, with restriction fragment length polymorphism (RFLP) analysis performed on five cases of active pulmonary TB in the home with the highest rate of TB showing unique RFLP patterns. CONCLUSION: The rate of active TB and TB infection in old age homes in Hong Kong is still high. Because treatment for latent TB carries a high risk for liver dysfunction in this population, clinicians and other healthcare workers need a high index of suspicion and to diagnose and treat this disease as early as possible to prevent transmission.