Timothy Kwok

Six-month randomized, placebo-controlled, double-blind, pilot clinical trial of curcumin in patients with Alzheimer disease.

To the Editors:Curcumin is a polyphenolic molecule that comprises approximately 5% of turmeric, giving the spice its color but not flavor. It is used in processed foods as a yellow coloring. 1 Because of its anti-inflammatory and antioxidant properties, curcumin has been tested in animal models of A

Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial.

BACKGROUND Whether Helicobacter pylori increases the risk of ulcers in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) is controversial. We hypothesised that eradication of H pylori infection would reduce the risk of ulcers for patients starting long-term NSAID treatment. METHODS Patients were enrolled if they were NSAID naïve, had a positive urea breath test, had dyspepsia or an ulcer history, and required long-term NSAID treatment. They were randomly assigned omeprazole triple therapy (eradication group) or omeprazole with placebo antibiotics (placebo group) for 1 week. All patients were given diclofenac slow release 100 mg daily for 6 months from randomisation. Endoscopy was done at 6 months or if severe dyspepsia or gastrointestinal bleeding occurred. The primary endpoint was the probability of ulcers within 6 months. Analyses were by intention to treat. FINDINGS Of 210 arthritis patients screened, 128 (61%) were positive for H pylori. 102 patients were enrolled, and 100 were included in the intention-to-treat analysis. H pylori was eradicated in 90% of the eradication group and 6% of the placebo group. Five of 51 eradication-group patients and 15 of 49 placebo-group patients had ulcers. The 6-month probability of ulcers was 12.1% (95% CI 3.1-21.1) in the eradication group and 34.4% (21.1-47.7) in the placebo group (p=0.0085). The corresponding 6-month probabilities of complicated ulcers were 4.2% (1.3-9.7) and 27.1% (14.7-39.5; p=0.0026). INTERPRETATION Screening and treatment for H pylori infection significantly reduces the risk of ulcers for patients starting long-term NSAID treatment.

Cognitive impairment and functional outcome after stroke associated with small vessel disease

Objectives: Although stroke associated with small vessel disease (SSVD) can induce both motor and cognitive impairment, the latter has received less attention. We aimed to evaluate the frequency of the varying severity levels of cognitive impairment, the determinants of severe cognitive impairment, and the association of cognitive impairment with functional outcome after SSVD. Methods: Consecutive patients admitted to hospital because of SSVD were assessed at 3 months after stroke. We performed a semi-structured clinical interview to screen for cognitive symptoms. Severity of cognitive symptoms was graded according to the Clinical Dementia Rating Scale (CDR). Performance on psychometric tests (Mini-Mental State Examination, Alzheimer’s Disease Assessment Scale (cognition subscale), Mattis Dementia Rating Scale (initiation/perseverence subscale; MDRS I/P)) of patients of different CDR gradings was compared with that of 42 healthy controls. Basic demographic data, vascular risk factors, stroke severity (National Institute of Health Stroke Scale; NIHSS), pre-stroke cognitive decline (Informant Questionnaire on Cognitive Decline in the Elderly; IQCODE), functional outcome (Barthel index; BI), Instrumental Activities Of Daily Living; IADL), and neuroimaging features (site of recent small infarcts, number of silent small infarcts, white matter changes) were also compared among the groups. Regression analyses were performed to find predictors of severe cognitive impairment and poor functional outcome. Results: Among the 75 included patients, 39 (52%) complained of cognitive symptoms. The number of patients in each CDR grading was as follows: 39 (52%) had a CDR of 0, 26 (34.7%) had a CDR of 0.5, 10 (13.3%) had a CDR of ⩾1. Pre-stroke IQCODE and previous stroke predicted CDR⩾1. The NIHSS was associated with more impaired BI. The NIHSS and MDRS I/P contributed most to impaired IADL. Conclusions: Half of the patients with SSVD complained of varying severity of cognitive problems 3 months after stroke. Pre-stroke cognitive decline and previous stroke predict severe cognitive impairment post stroke. Stroke severity and executive dysfunction contribute most to a poor functional outcome.

Associated factors and health impact of sarcopenia in older chinese men and women: a cross-sectional study.

Background: Sarcopenia is increasingly being recognized as a feature of frailty in old age and is associated with unfavorable health outcomes in Western populations. Little is known about sarcopenia among Asian elderly populations. Objectives: The study was undertaken to study the association between sarcopenia and common chronic illnesses, lifestyle factors, psychosocial well-being and physical performance. Methods: 4,000 community-dwelling Chinese elderly ≧65 years were recruited. Medical illnesses, cigarette smoking, alcohol consumption, physical activity level and psychosocial well-being scores were recorded. Physical performance measured included grip strength, timed chair-stands, stride length and a timed 6-meter walk. Muscle mass was measured using dual-energy X-ray absorptiometry. Relationships between appendicular skeletal muscle mass (ASM/ht2) and multiple variables were analyzed using uni- and multivariate analyses. Results: Mean ASM/ht2 was 7.19 and 6.05 kg/m2 in men and women respectively. Older age, cigarette smoking, chronic lung disease, atherosclerosis, underweight, and physical inactivity were associated with low adjusted ASM, which was in turn associated with poorer physical well-being in men. After adjustment to age, lower appendicular muscle mass was associated with weaker grip strength in both sexes. In men, lower limb tests (chair-stands, walking speed and step length) were not related to ASM, while in women, lower muscle mass was not associated with poorer lower limb muscle performance. Conclusions: Sarcopenia in community-dwelling older Chinese men and women was associated with cigarette smoking, chronic illnesses, underweight, physical inactivity, poorer well-being and upper limb physical performance.

A Meta‐Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX

Trabecular bone score (TBS) is a gray‐level textural index of bone microarchitecture derived from lumbar spine dual‐energy X‐ray absorptiometry (DXA) images. TBS is a bone mineral density (BMD)‐independent predictor of fracture risk. The objective of this meta‐analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual‐level data from 17,809 men and women in 14 prospective population‐based cohorts. Baseline evaluation included TBS and the FRAX risk variables, and outcomes during follow‐up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities, and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1 SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% confidence interval [CI] 1.35–1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10‐year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR = 1.32, 95% CI 1.24–1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95% CI 1.65–1.87 versus 1.70, 95% CI 1.60–1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

Compromised Bone Marrow Perfusion in Osteoporosis

A link between bone blood flow and osteoporosis may exist. Outside of the spine, the proximal femur is the most common site of osteoporotic fracture and is also an area prone to avascular necrosis and fracture nonunion. This study of the proximal femur investigates the relationship between BMD, bone marrow fat content, bone perfusion, and muscle perfusion. One hundred twenty healthy female subjects (mean age, 74 yr; age range, 67–89 yr) underwent DXA examination of the hip, proton MR spectroscopy, and dynamic contrast‐enhanced MR imaging of the right proximal femur, acetabulum, and adductor thigh muscle. In all bone areas examined (femoral head, femoral neck, femoral shaft, acetabulum), perfusion indices (maximum enhancement, enhancement slope) were significantly reduced in subjects with osteoporosis compared with subjects with osteopenia or normal BMD. Adductor muscle perfusion was not affected by change in BMD. As marrow perfusion decreased in the proximal femur, marrow fat increased (r = 0.827). This increase in fat content seemed to account for the decrease in marrow perfusion more than a reduction in BMD. For normal BMD subjects, perfusion parameters in the femoral head were one third of those in the femoral neck or shaft and one fifth of those in the acetabulum. Perfusion throughout the proximal femur is reduced in osteoporotic subjects compared with osteopenic and normal subjects. This reduction in perfusion only affects bone and not those tissues outside of bone with the same blood supply. As bone perfusion decreased, there was a corresponding increase in marrow fat.

Functional Decline in Cognitive Impairment - The Relationship between Physical and Cognitive Function

Background: Physical function decline is associated with dementia, which might either be mediated by the coexisting sarcopenia or directly related to the impaired cognition. Our objectives are to examine the relationship between cognitive function and performance-based physical function and to test the hypothesis that cognitive function is related to poor physical function independent of muscle mass. Methods: We measured muscle strength, performance-based physical function and muscle mass using dual-energy X-ray absorptiometry and cognitive function using the cognitive part of the Community Screening Instrument of Dementia (CSI-D) in 4,000 community-dwelling Chinese elderly aged >65 years. A CSI-D cognitive score of >28.40 was considered as cognitively impaired. The effect of cognitive impairment on muscle strength and physical function was analyzed by multivariate analysis with adjustment for age, appendicular skeletal mass (ASM), the Physical Activity Scale for the Elderly (PASE) and other comorbidities. Results: In both genders, the cognitively impaired (CSI-D cognitive score >28.40) group had a weaker grip strength (–5.10 kg, p < 0.001 in men; –1.08 kg in women, p < 0.001) and performed worse in the two physical function tests (in men, 6-meter walk speed, –0.13 m/s, p < 0.001, chair stand test, 1.42 s, p < 0.001; in women, 6-meter walk speed, –0.08 m/s, p < 0.001, chair stand test, 1.48 s, p < 0.001). After adjustment for age, ASM, PASE and other comorbidities, significant differences in grip strength (–2.60 kg, p < 0.001 in men; –0.49 kg, p = 0.011 in women) and the two physical function tests persisted between the cognitively impaired and nonimpaired group (in men, 6-meter walk speed, –0.072 m/s, p < 0.001, chair stand test, 0.80 s, p = 0.045; in women, 6-meter walk speed, –0.049 m/s, p < 0.001, chair stand test, 0.98 s, p < 0.001). Conclusions: Poor physical function and muscle strength coexisted with cognitive impairment. This relationship was independent of muscle mass. It is likely therefore that the functional decline in dementia might be related directly to factors resulting in cognitive impairment independently of the coexisting sarcopenia.

The Use of Armspan in Nutritional Assessment of the Elderly

The use of body mass index (BMI) in the elderly is limited by the measurement of height which is often unreliable. Armspan approximates to height at maturity. It may, therefore, be an alternative to height in calculating BMI. We studied the relationship between height and armspan in 101 elderly men and women. A comparison of BMI by height and armspan was made. The correlation between height and armspan was 0.93. Armspan could be estimated by doubling halfspan (recumbent). The mean difference between BMI by height and armspan was 1.79 (SD 1.11) kg/M2. We concluded that armspan is a reliable and practical estimate of height in the non‐ambulant elderly. There is a case for the use of armspan instead of height in the determination of BMI in the elderly.

Cognitive Tests to Detect Dementia A Systematic Review and Meta-analysis

IMPORTANCE Dementia is a global public health problem. The Mini-Mental State Examination (MMSE) is a proprietary instrument for detecting dementia, but many other tests are also available. OBJECTIVE To evaluate the diagnostic performance of all cognitive tests for the detection of dementia. DATA SOURCES Literature searches were performed on the list of dementia screening tests in MEDLINE, EMBASE, and PsychoINFO from the earliest available dates stated in the individual databases until September 1, 2014. Because Google Scholar searches literature with a combined ranking algorithm on citation counts and keywords in each article, our literature search was extended to Google Scholar with individual test names and dementia screening as a supplementary search. STUDY SELECTION Studies were eligible if participants were interviewed face to face with respective screening tests, and findings were compared with criterion standard diagnostic criteria for dementia. Bivariate random-effects models were used, and the area under the summary receiver-operating characteristic curve was used to present the overall performance. MAIN OUTCOMES AND MEASURES Sensitivity, specificity, and positive and negative likelihood ratios were the main outcomes. RESULTS Eleven screening tests were identified among 149 studies with more than 49,000 participants. Most studies used the MMSE (n = 102) and included 10,263 patients with dementia. The combined sensitivity and specificity for detection of dementia were 0.81 (95% CI, 0.78-0.84) and 0.89 (95% CI, 0.87-0.91), respectively. Among the other 10 tests, the Mini-Cog test and Addenbrookes Cognitive Examination-Revised (ACE-R) had the best diagnostic performances, which were comparable to that of the MMSE (Mini-Cog, 0.91 sensitivity and 0.86 specificity; ACE-R, 0.92 sensitivity and 0.89 specificity). Subgroup analysis revealed that only the Montreal Cognitive Assessment had comparable performance to the MMSE on detection of mild cognitive impairment with 0.89 sensitivity and 0.75 specificity. CONCLUSIONS AND RELEVANCE Besides the MMSE, there are many other tests with comparable diagnostic performance for detecting dementia. The Mini-Cog test and the ACE-R are the best alternative screening tests for dementia, and the Montreal Cognitive Assessment is the best alternative for mild cognitive impairment.

BMI, Body Composition, and Physical Functioning in Older Adults

Objective: Recent studies have emphasized the importance of muscle and fat mass in relation to age‐related decline in physical function. Our objective was to determine whether BMI, as a surrogate measurement of fat mass, may be used as a measure of risk factor for physical functioning in older adults and whether body composition measurements confer any advantage over BMI.