Yih Yuen

Case-control study of diffusion tensor imaging in Parkinson’s disease

Background: Preliminary work has shown that diffusion tensor MRI (DTI) may contribute to the diagnosis of Parkinson’s disease (PD). Objectives: We conducted a large, prospective, case control study to determine: (1) if fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in the basal ganglia and substantia nigra are different between patients with PD and healthy controls; and (2) the predictive value of these parameters and their clinical utility. Methods: DTI imaging was carried out in patients with PD and controls. FA and ADC values were obtained from various brain structures on the DTI scan using the diffusion tensor taskcard. The structures studied were: caudate, putamen, globus pallidus, thalamus and substantia nigra. Results: 151 subjects (73 PD patients, 41 men, 32 women; mean age 63.6 years) and 78 age and sex matched control subjects were studied. The FA value of the substantia nigra in patients with PD was lower compared with controls (0.403 vs 0.415; p = 0.001). However, no significant differences were demonstrated for FA or ADC values of other structures. Multiple regression analysis revealed that the clinical severity of PD correlated inversely with the FA value in the substantia nigra in patients with PD (regression coefficient −0.019). No single FA value had both a high positive and negative predictive power for PD. Conclusions: We demonstrated in a large, prospective, case control study that the FA value in the substantia nigra on DTI was lower in PD compared with healthy controls, and correlated inversely with the clinical severity of PD. Further longitudinal studies would be helpful to assess the clinical utility of serial FA measurements of the substantia nigra in objective quantification of disease progression and monitoring of the therapeutic response.

PINK1 mutations in sporadic early‐onset Parkinson's disease

Pathogenic PINK1 mutations have been described in PARK6‐linked Parkinsons disease (PD) patients of Asian origin. However, data on the frequency of PINK1 mutations in sporadic early‐onset Parkinsons disease (EOPD) Asian patients are lacking. The objectives of this study were to report the frequency of PINK1 mutations of sporadic EOPD in an Asian cohort comprising of ethnic Chinese, Malays, and Indians, and to highlight a PINK1‐positive patient who presented with restless legs symptoms. Eighty consecutive sporadic EOPD patients from the movement disorder clinics of two major tertiary institutions in the country were included. We performed sequence analysis of all the coding and exon–intron junctions of the PINK1 using specific primer sets. In addition, we genotyped polymorphisms detected from the analysis in a group of sporadic PD patients and controls. Three different mutations (two homozygous nonsense and one heterozygous missense) in the putative kinase domain were found in three patients, giving a 3.7% frequency of PINK1 mutations in our EOPD cohort. All the mutations were absent in 200 healthy controls. One patient with a novel homozygous nonsense PINK1 mutation presented unusually with restless legs symptoms. Separately, analysis of the frequency of four PINK1 polymorphisms in a group of sporadic PD and controls did not reveal any significant differences. We highlight a 3.7% frequency of PINK1 mutations in an Asian cohort (ethnic Chinese, Malay, and Indian) of EOPD. The phenotypic spectrum associated with PINK1‐positive patients may be wider than previously reported. Polymorphisms of PINK1 do not appear to modulate risk of PD in our population.

Age-Associated Gait Changes in the Elderly: Pathological or Physiological?

AIM To examine the role of disease-related factors and age-related physiological changes in affecting gait speed and stride length in the elderly. SUBJECTS 925 men and 890 women aged 70 years and above who were ambulant, recruited by random sampling stratified according to age and sex, from all recipients of Old Age and Disability Allowance in Hong Kong. DESIGN Gait was assessed by measuring the time taken and the number of steps required to complete a 16-foot walk. Information on health and functional status, cognitive function, and depressive symptoms was collected, and anthropometric indices obtained. Factors affecting walking speed and stride were examined in the overall population and also after excluding those with physical disability or diseases. RESULTS Results were analyzed separately for men and women since mean walking speed was slower in women, who also took a larger number of steps. Age, coexisting disease, leg or back pain, poor vision, low level of physical activity, functional and cognitive impairment, high depressive symptom score, and anthropometric indices were all negatively associated with walking speed. Fallers also had slower speed. After excluding those with diseases or physical impairment, multivariate analysis showed that the only factors affecting speed were age in men, and age, height, and level of physical activity in women. Age and height were factors associated with stride length in men, and height only for women. CONCLUSION Both disease-related factors as well as age-related physiological changes contribute to the decline in walking speed and stride length.

Analysis of LRRK2 functional domains in nondominant Parkinson disease.

A comprehensive sequence analysis of 29 exons that code for the functional domains of LRRK2 in 160 nondominant Parkinson disease (PD) patients was performed. Novel variant screening in a further 470 sporadic PD patients and 630 controls revealed two novel variants (R1067Q and IVS33 + 6 T>A), which are likely to be pathogenic in five patients. One patient presented initially with a typical essential tremor phenotype, expanding the phenotypic spectrum of LRRK2 mutations.

Prevalence of Cognitive Impairment and Associated Factors among Elderly Hong Kong Chinese Aged 70 Years and Over

The prevalence of cognitive impairment was determined in a random age- and sex-stratified sample of 2,011 elderly Hong Kong Chinese, aged 70 years and over, consisting of subjects living in the community and in institutions. The Information/Orientation Section of the Clifton Assessment Procedure was used as the screening instrument using a cutoff point of 7. The overall age-adjusted prevalence was 5% for men and 22% for women, and 15% for both sexes combined. Univariate analysis identified the following associated factors in order of magnitude of the odds ratio: age; history of Parkinsons disease; functional disability; female sex; low educational level; low social class; history of stroke, and low monthly income. Other diseases, such as heart disease, hypertension, chronic lung diseases or diabetes, were not associated factors. In multivariate analysis, all the above factors remained significant with the exception of a history of stroke. The prevalence figures are comparable to other Caucasian and Chinese studies, and the associated factors identified suggest that there may be room for prevention.

Cardiovascular Risk Factors and 18-Month Mortality and Morbidity in an Elderly Chinese Population Aged 70 Years and Over

Objective: To determine the influence of some cardiovascular risk factors (hypertension, diabetes mellitus, smoking habit, physical activity, obesity, adverse lipid profile) in elderly Chinese aged 70 years and over, on overall mortality and morbidity from stroke and ischaemic heart disease. Design: Longitudinal study relating 18-month outcome to baseline values. Subjects: 2,032 subjects (999 men, 1,033 women), mean age 80 years, recruited by random sampling of the Old Age and Disability Allowance Schemes, which covers 90% of the Hong Kong elderly subjects, stratified by sex and 5-year age groups from 70 years onwards. Methods: At baseline, subjects were visited by interviewers to collect information regarding medical conditions, smoking habit, physical activity, and to measure their height, weight, skinfold thickness, and waist/hip ratio. A follow-up survey was carried out 18 months later to establish the development of any new stroke or ischaemic heart disease, and to note any deaths and the cause of such deaths from death certification. Results: In multivariate analysis overall mortality was negatively associated with body mass index and participation in physical activity, after adjusting for age and sex. Death from stroke was associated with a higher systolic blood pressure at baseline. Among survivors, the only significant associations observed were a negative association between body mass index and the development of heart disease, and a positive association between systolic blood pressure and development of stroke. Conclusions: Few associations between cardiovascular risk factors and morbidity and mortality were demonstrated in elderly Chinese with a mean age of 80 years. The only modifiable risk factor appears to be systolic blood pressure.

Age and marital status are major factors associated with institutionalisation in elderly Hong Kong Chinese.

STUDY OBJECTIVE--To determine the need for long term institutional care for elderly Chinese living in Hong Kong and factors associated with institutional living. DESIGN--Survey by interviewer administered questionnaire of a stratified random sample of all recipients of old age or disability allowance covering 90% of the population. SETTING--Survey performed in Hong Kong, a city on the south coast of China with an area of 1070 km2 and approximately six million people. PARTICIPANTS--A total of 2032 subjects aged 70 years and over (999 men, 1033 women) participated. MAIN RESULTS--Overall, 16% of the elderly live in institutions. The percentage is higher in women and in the older age group (81% for those aged 80 years and over). After adjusting for age and sex, the following factors were positively associated with institutionalisation: poor cognitive function, measures of functional disability, poor vision, Parkinsons disease, stroke, and past fractures. Multivariate analysis identified age and marital status as associated factors with the highest odds ratio (13.6 and 7.1 respectively), followed by various disability indicators. CONCLUSION--The survey shows that requirements for long term care places are unlikely to be much affected by preventive measures, and would need to increase by about 30% by 2000 to cope with the projected increase in the number of elderly aged 70 years and over. Measures to provide sufficient trained personnel and policy for regulation of standards should be made.

Respiratory symptoms in elderly Chinese living in Hong Kong

Respiratory diseases can cause considerable disability in the elderly because of their limited respiratory reserve as a result of ageing. We have investigated the prevalence of respiratory symptoms and diseases in elderly Chinese in Hong Kong and compared these data with those in elderly Caucasian populations. Two thousand and thirty two (999 male and 1,033 female) subjects, selected by age-stratified random sampling from a register of Hong Kong residents aged 70 yrs and over were interviewed to complete a respiratory questionnaire. Total serum immunoglobulin E (IgE) was measured in 195 subjects. At least one respiratory symptom was reported by 56% of subjects. The most frequently reported symptoms were morning phlegm (26%), chronic cough with phlegm (10%) and wheeze in the past 12 months (8%). Of the self-reported diseases, the commonest was chronic bronchitis (7%), followed by asthma (5%), pulmonary tuberculosis (3%) and emphysema (2%). Of the 218 subjects with obstructive airway diseases, 128 (59%) had sought medical advice in the past 12 months. The most important determinants for respiratory symptoms and diseases were smoking and social class. Total serum IgE was significantly higher in current smokers than nonsmokers and also in those with chronic cough and phlegm than those without these complaints. Our study shows that respiratory ailments in Hong Kong elderly are as common as those reported in Sweden and the USA but less than those in England.

An estimate of chronic disease burden and some economic consequences among the elderly Hong Kong population.

OBJECTIVES: To estimate the burden of chronic disease for an elderly Chinese population aged 70 years and over, and to illustrate the use of this information in estimating the economic consequences of disease burden using stroke as an example. PARTICIPANTS: A total of 1902 subjects recruited by random sampling of the old age and disability allowance schemes, which cover over 90% of the Hong Kong elderly population, stratified by sex and five year age groups from age 70 years onwards. METHOD: Information was collected on 10 medical conditions at baseline: arthritis, hypertension, cardiac disease, stroke, chronic obstructive airways disease, peptic ulcer, diabetes mellitus, osteoporotic fracture, malignancy, and dementia. A follow up survey was carried out after 18 months to determine the occurrence of new disease and the number with disease who had died. Disease burden is calculated as the number with disease at baseline plus the number developing new disease minus the number who had died. RESULTS: Disease burden figures were highest for arthritis, hypertension, cardiac disease, and peptic ulcer, and were higher in the 70-79 age group than the 80+ age group for some diseases. For stroke, the economic cost based on a population projection for 2001 was estimated to be around HK

Association between caffeine intake and risk of Parkinson's disease among fast and slow metabolizers

1,900,000,000, or US