Wee Shiong Lim

Tan Tock Seng Hospital, Tumasik, Singapore

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Publications (56)249.37 Total impact

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    ABSTRACT: Objectives: To examine the relationships between tea consumption habits and incident neurocognitive disorders (NCD) and explore potential effect modification by gender and the apolipoprotein E (APOE) genotype. Design: Population-based longitudinal study. Setting: The Singapore Longitudinal Aging Study (SLAS). Participants: 957 community-living Chinese elderly who were cognitively intact at baseline. Measurements: We collected tea consumption information at baseline from 2003 to 2005 and ascertained incident cases of neurocognitive disorders (NCD) from 2006 to 2010. Odds ratio (OR) of association were calculated in logistic regression models that adjusted for potential confounders. Results: A total of 72 incident NCD cases were identified from the cohort. Tea intake was associated with lower risk of incident NCD, independent of other risk factors. Reduced NCD risk was observed for both green tea (OR=0.43) and black/oolong tea (OR=0.53) and appeared to be influenced by the changing of tea consumption habit at follow-up. Using consistent non-tea consumers as the reference, only consistent tea consumers had reduced risk of NCD (OR=0.39). Stratified analyses indicated that tea consumption was associated with reduced risk of NCD among females (OR=0.32) and APOE ε4 carriers (OR=0.14) but not males and non APOE ε4 carriers. Conclusion: Regular tea consumption was associated with lower risk of neurocognitive disorders among Chinese elderly. Gender and genetic factors could possibly modulate this association.
    No preview · Article · Jan 2016 · The Journal of Nutrition Health and Aging
  • Lim Jun Pei · Iris Li Tianzhi · Wee Shiong Lim

    No preview · Article · Dec 2015 · Journal of the American Geriatrics Society
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    ABSTRACT: Background: Frailty and cognitive impairment are seemingly distinct syndromes, but have a shared vulnerability to stress in older adults, resulting in poorer outcomes. Although there has been recent interest in cognitive frailty, frailty transitions in relation to cognitive deterioration in older adults with cognitive impairment have not yet been well studied. We thus aim to study frailty transitions and change in cognitive status over 1-year follow-up among subjects with cognitive impairment attending a tertiary Memory Clinic. Methods: This is a prospective cohort study of mild cognitive impairment (MCI) and mild-moderate Alzheimer's disease (AD) community-dwelling subjects. We obtained data on clinical measures, muscle mass and physical performance measures. Cognitive status was measured using Chinese Mini-Mental State Examination (CMMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores. We measured gait speed, hand grip strength, exhaustion and weight loss at baseline, 6 and 12 months to classify subjects according to the modified Fried criteria (involving strength, gait speed, body composition and fatigue) into non-frail (<2 frail categories) and frail categories (≥2 frail categories). Frailty transitions between baseline and 12-months were assessed. We performed random effects statistical modelling to ascertain baseline predictors of longitudinal frailty scores for all subjects and within MCI subgroup. Results: Among 122 subjects comprising 41 MCI, 67 mild and 14 moderate AD, 43.9, 35.8 and 57.1 % were frail at baseline respectively. Frailty status regressed in 32.0 %, remained unchanged in 36.0 %, and progressed in 32.0 % at 12 months. Random effects modelling on whole group showed longitudinal CDR-SB scores (coeff 0.09, 95 % confidence interval (CI) 0.03-0.15) and age (coeff 0.04, 95 % CI 0.02-0.07) to be significantly associated with longitudinal frailty score. Among MCI subjects, only female gender (coeff 1.28, 95 % CI 0.21-2.36) was associated with longitudinal frailty score, while mild-moderate AD subjects showed similar results as those of the whole group. Conclusions: This is the first study to show longitudinal frailty state transitions in cognitively-impaired older adults. Frailty transitions appear to be independent of progression in cognitive status in earliest stages of cognitive impairment, while mild-moderate AD subjects showed associations with age and cognitive deterioration. The potential for cognitive frailty as a separate therapeutic entity for future physical frailty prevention requires further research with a suitably powered study over a longer follow-up period.
    Preview · Article · Dec 2015 · BMC Geriatrics
  • L. Tay · W.S. Lim · M. Chan · R.J. Ye · M.S. Chong
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    ABSTRACT: Objectives: To examine the independent and combined effects of inflammation and endocrine dysregulation on (i) baseline frailty status and (ii) frailty progression at one year, among cognitively impaired community dwelling older adults. Design: Prospective cohort study. Setting: Tertiary Memory Clinic. Methods: We recruited patients with mild cognitive impairment and mild-moderate Alzheimer’s disease. Physical frailty status was assessed at baseline and 1-year. Blood biomarkers of systemic inflammation [interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α)] and anabolic hormones [insulin-like growth factor-1 (IGF-1), dehydroepiandrosterone sulphate (DHEAS)] were measured at baseline and examined in relation to physical frailty status at baseline and progression at 1-year. Each subject was categorized as (i) neither pro-inflammatory nor endocrine deficient, (ii) pro-inflammatory (IL-6 or TNF-α, or both, being in highest quartile) but not endocrine deficient, (iii) endocrine deficient (IGF-1 or DHEAS, or both, being in lowest quartile) but not pro-inflammatory and (iv) both pro-inflammatory and endocrine deficient. Results: Twenty (20.2%) of 99 subjects were physically frail at baseline. There was no association between severity of cognitive impairment and baseline frailty status, but the frail group had significantly greater hippocampal atrophy (median MTA: 2 (2-3) vs 1 (1-2), p=0.010). TNF-α was significantly higher in subjects who were physically frail at baseline (median TNF-α: 1.30 (0.60-1.40) vs 0.60 (0.50-1.30) pg/mL, p=0.035). In multiple logistic regression adjusted for age and gender, a pro-inflammatory state in the absence of concomitant endocrine deficiency was significantly associated with physical frailty at baseline (OR=4.99, 95% C.I 1.25-19.88, p=0.023); this was no longer significant when MTA score was included in the model. Isolated pro-inflammatory state (without endocrine deficiency) significantly increased the odds of frailty progression (OR=4.06, 95% CI 1.09-15.10, p=0.037) at 1-year. The combination pro-inflammatory and endocrine deficient state was not significantly associated with either baseline or progressive physical frailty. Conclusion: A pro-inflammatory state exerts differential effects on physical frailty, contributing to the increased risk of baseline and progressive frailty only in the absence of a concomitant endocrine deficient state, with potential mediation via neurodegeneration.
    No preview · Article · Nov 2015 · The Journal of Nutrition Health and Aging
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    ABSTRACT: Introduction: Novel oral anticoagulants (NOACs) expanded the options for stroke prevention in atrial fibrillation (AF). Earlier studies comparing their relative effectiveness and safety typically do not incorporate age-related differences or postmarketing studies. This study aimed to summarize and compare clinical and safety outcomes of oral antithrombotics for stroke prevention in AF in younger (65-74 years) and older (≥75 years) elderly. Methods: We searched PubMed, Embase, and The Cochrane Library from inception through May 1, 2015, for randomized and nonrandomized studies comparing NOACs, warfarin, and aspirin in elderly with AF. Stroke and systemic embolism (SSE) and major bleeding (MB) are the main outcomes. We also studied secondary outcomes of ischemic stroke, all-cause mortality, intracranial bleeding, and gastrointestinal bleeding. Results: Of 5255 publications identified, 25 randomized controlled trials and 24 nonrandomized studies of 897,748 patients were included. NOACs reduced the risk of SSE compared with warfarin (rate ratios [RRs] range from 0.78-0.82). Relative to SSE, NOACs demonstrated a smaller benefit for ischemic stroke (dabigatran 110 mg, RR 1.08; edoxaban, 1.00; apixaban, 0.99). On the contrary, aspirin was associated with a significantly higher risk of SSE, ischemic stroke, and mortality than warfarin or NOACs (RR > 1), particularly in older elderly. Regarding safety, medium-dose aspirin (100-300 mg daily) and aspirin/clopidogrel combination showed an increased risk of MB compared with warfarin (RR 1.17 and 1.15, respectively), as per dabigatran 150 mg and rivaroxaban in older elderly (RR 1.17 and 1.12, respectively). Among the NOACs, dabigatran 150 mg conferred greater gastrointestinal bleeding risk compared with warfarin (RR 1.51), whereas rivaroxaban (RR 0.73) demonstrated less benefit of reduced intracranial bleeding than other NOACs (RRs range 0.39-0.46). Conclusions: Lower rates of SSE and intracranial bleeding were observed with the NOACs compared with warfarin. Dabigatran 150 mg and rivaroxaban were associated with higher rates of MB in older elderly.
    No preview · Article · Nov 2015 · Journal of the American Medical Directors Association
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    ABSTRACT: Objective: This study examines the International Classification of Functioning, Disability, and Health model (ICF) using a data set of 2,563 community-dwelling elderly with disease-independent measures of mobility, physical activity, and social networking, to represent ICF constructs. Method: The relationship between chronic disease and disability (independent and dependent variables) was examined using logistic regression. To demonstrate variability in activity performance with functional impairment, graphing was used. The relationship between functional impairment, activity performance, and social participation was examined graphically and using ANOVA. The impact of cognitive deficits was quantified through stratifying by dementia. Results: Disability is strongly related to chronic disease (Wald 25.5, p < .001), functional impairment with activity performance (F = 34.2, p < .001), and social participation (F= 43.6, p < .001). With good function, there is considerable variability in activity performance (inter-quartile range [IQR] = 2.00), but diminishes with high impairment (IQR = 0.00) especially with cognitive deficits. Discussion: Environment modification benefits those with moderate functional impairment, but not with higher grades of functional loss.
    Preview · Article · Oct 2015 · Journal of Aging and Health

  • No preview · Article · Jul 2015
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    L Feng · M.-S Chong · W.-S Lim · T.-S Lee · E.-H Kua · T.-P Ng · Lei Feng
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    ABSTRACT: The availability of empirical data from human studies in recent years have lend credence to the old axiomatic wisdom that health benefits of tea drinking extend to the area of cognition. Specifically, there is increasing interest as to whether tea drinking can delay or even prevent the onset of Alzheimer's disease (AD). Data from several cross-sectional studies have consistently shown that tea drinking is associated with better performance on cognitive tests. This association is supported by longitudinal data from the Singapore Longitudinal Aging Study, the Chinese Longitudinal Healthy Longevity Survey and the Cardiovascular Health Study. The only two published longitudinal analyses on clinical outcome reported conflicting results: one study reported that mid-life tea drinking was not associated with risk reduction of Alzheimer's disease in late life while the other one found that green tea consumption reduced the incidence of dementia or mild cognitive impairment. Two small trials from Korea and Japan reported encouraging but preliminary results. While the existing evidence precludes a definite conclusion as to whether tea drinking can be an effective and simple lifestyle preventive measure for AD, further research involving longer-term longitudinal studies and randomized controlled trials is clearly warranted to shed light on this topic of immense public health interest. Biological markers of tea consumption and Alzheimer diseases should be employed in future research to better delineate the underlying mechanisms of tea drinking's protective effect on cognition.
    Full-text · Article · Jun 2015
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    ABSTRACT: To investigate the utility of the Severe Impairment Rating Scale (SIRS) as a cognitive assessment tool among nursing home residents with advanced dementia, we conducted a cross-sectional study of 96 residents in 3 nursing homes with Functional Assessment Staging Test (FAST) stage 6a and above. We compared the discriminatory ability of SIRS with the Chinese version of Mini-Mental State Examination, Abbreviated Mental Test, and Clock Drawing Test. Among the cognitive tests, SIRS showed the least "floor" effect and had the best capacity to distinguish very severe (FAST stages 7d-f) dementia (area under the curve 0.80 vs 0.46-0.76 for the other tools). The SIRS had the best correlation with FAST staging (r = -.59, P < .01) and, unlike the other 3 tools, exhibited only minimal change in correlation when adjusted for education and ethnicity. Our results support the utility of SIRS as a brief cognitive assessment tool for advanced dementia in the nursing home setting. © The Author(s) 2015.
    No preview · Article · May 2015 · American Journal of Alzheimer s Disease and Other Dementias
  • W. Lim · M. Chong · L. Tay · N. Ali · A. Yeo · M. Chan

    No preview · Conference Paper · Apr 2015
  • Wee Shiong Lim · Y Y Ding

    No preview · Article · Feb 2015 · Annals of the Academy of Medicine, Singapore
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    ABSTRACT: The Zarit Burden Interview allows caregiver burden to be interpreted from a total score. However, recent studies propose a multidimensional Zarit Burden Interview model. This study aims to determine the agreement between unidimensional (UD) and multidimensional (MD) classification of burden, and differences in predictors among identified groups. We studied 165 dyads of dementia patients and primary caregivers. Caregivers were dichotomized into low-burden and high-burden groups based upon: (1) UD score using quartile cutoffs; and (2) MD model via exploratory cluster analysis. We compared UD versus MD 2×2 classification of burden using κ statistics. Caregivers not showing agreement by either definition were classified as "intermediate" burden. We performed binary logistic regression to ascertain differences in predictive factors. The 2 models showed moderate agreement (κ=0.72, P<0.01), yielding 104 low, 20 intermediate (UD "low burden"/MD "high burden"), and 41 high-burden caregivers. Neuropsychiatric symptoms [odds ratio (OR)=1.27, P=0.003], coresidence (OR=6.32, P=0.040), and decreased caregiving hours (OR=0.99, P=0.018) were associated with intermediate burden, whereas neuropsychiatric symptoms (OR=1.21, P=0.001) and adult children caregivers (OR=2.80, P=0.055) were associated with high burden. Our results highlight the differences between UD and MD classification of caregiver burden. Future studies should explore the significance of the noncongruent intermediate group and its predictors.
    No preview · Article · Feb 2015 · Alzheimer Disease and Associated Disorders
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    ABSTRACT: A new interprofessional geriatric medicine curriculum was recently introduced at a large undergraduate Asian medical school. A longitudinal controlled interventional cohort study was conducted to evaluate the effect of the new curriculum on the knowledge and attitudes of medical students. The medical students under the new curriculum formed the intervention cohort, and those under the former curriculum formed the control cohort. To test knowledge, the University of California at Los Angeles (UCLA) geriatrics knowledge test (GKT) was used in Year 2 and the University of Michigan GKT in Year 5. Geriatrics attitudes were evaluated using the UCLA geriatrics attitudes test in Years 2 and 5. Not surprisingly, geriatrics knowledge at the end of Year 5 of medical school was enhanced to a greater degree in the intervention cohort than the control cohort, although improvements in geriatrics attitudes in each cohort were of similar magnitude by the end of Year 5, suggesting that factors other than a formal geriatrics curriculum influenced the improvements in geriatrics attitudes. This article is one of few published on the effectiveness of geriatrics curricular innovations using validated knowledge and attitude outcomes in a longitudinal controlled study design and will be useful to other medical institutions seeking to improve the geriatrics knowledge and attitudes of their students. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
    Full-text · Article · Feb 2015 · Journal of the American Geriatrics Society
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    ABSTRACT: To examine diagnostic agreement between Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) Neurocognitive Disorders (NCDs) criteria and DSM, Fourth Edition (DSM-IV) criteria for dementia and International Working Group (IWG) criteria for mild cognitive impairment (MCI) and DSM-V's impact on diagnostic classifications of NCDs. The authors further examined clinical factors for discrepancy in diagnostic classifications between the different operational definitions. Using a cross-sectional study in tertiary memory clinic, the authors studied consecutive new patients aged 55 years or older who presented with cognitive symptoms. Dementia severity was scored based on the Clinical Dementia Rating scale (CDR). All patients completed neuropsychological evaluation. Agreement in diagnostic classifications between DSM-IV/IWG and DSM-V was examined using the kappa test and AC1 statistic, with multinomial logistic regression for factors contributing to MCI reclassification as major NCDs as opposed to diagnostically concordant MCI and dementia groups. Of 234 patients studied, 166 patients achieved concordant diagnostic classifications, with overall kappa of 0.41. Eighty-six patients (36.7%) were diagnosed with MCI and 131 (56.0%) with DSM-IV-defined dementia. With DSM-V, 40 patients (17.1%) were classified as mild NCDs and 183 (78.2%) as major NCDs, representing a 39.7% increase in frequency of dementia diagnoses. CDR sum-of-boxes score contributed independently to differentiation of MCI patients reclassified as mild versus major NCDs (OR: 0.01; 95% CI: 0-0.09). CDR sum-of-boxes score (OR: 5.18; 95% CI: 2.04-13.15), performance in amnestic (OR: 0.14; 95% CI: 0.06-0.34) and language (Boston naming: OR: 0.52; 95% CI: 0.29-0.94) tests, were independent determinants of diagnostically concordant dementia diagnosis. The authors observed moderate agreement between the different operational definitions and a 40% increase in dementia diagnoses with operationalization of the DSM-V criteria. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jan 2015 · The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry
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    ABSTRACT: Background: The Montreal Cognitive Assessment (MoCA) was developed as a screening instrument for mild cognitive impairment (MCI). We evaluated the MoCA's test performance by educational groups among older Singaporean Chinese adults. Method: The MoCA and Mini-Mental State Examination (MMSE) were evaluated in two independent studies (clinic-based sample and community-based sample) of MCI and normal cognition (NC) controls, using receiver operating characteristic curve analyses: area under the curve (AUC), sensitivity (Sn), and specificity (Sp). Results: The MoCA modestly discriminated MCI from NC in both study samples (AUC = 0.63 and 0.65): Sn = 0.64 and Sp = 0.36 at a cut-off of 28/29 in the clinic-based sample, and Sn = 0.65 and Sp = 0.55 at a cut-off of 22/23 in the community-based sample. The MoCA's test performance was least satisfactory in the highest (>6 years) education group: AUC = 0.50 (p = 0.98), Sn = 0.54, and Sp = 0.51 at a cut-off of 27/28. Overall, the MoCA's test performance was not better than that of the MMSE. In multivariate analyses controlling for age and gender, MCI diagnosis was associated with a <1-point decrement in MoCA score (η(2) = 0.010), but lower (1-6 years) and no education was associated with a 3- to 5-point decrement (η(2) = 0.115 and η(2) = 0.162, respectively). Conclusion: The MoCA's ability to discriminate MCI from NC was modest in this Chinese population, because it was far more sensitive to the effect of education than MCI diagnosis.
    Full-text · Article · Jan 2015 · Dementia and Geriatric Cognitive Disorders
  • Aik Phon Chew · Wee Shiong Lim · Keng Teng Tan

    No preview · Article · Oct 2014 · Journal of the American Geriatrics Society
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    ABSTRACT: We previously reported TOMM40 to be significantly down-regulated in whole blood of Alzheimer's disease (AD) subjects at baseline and after one-year. In this longitudinal follow-up study of TOMM40 expression up to 2 years, we performed 6-monthly assessments for the first year and 2nd year blood sampling on 27 probable AD subjects compared with age- and gender-matched controls. TOMM40 gene expression remained significantly lower in AD patients at all time-points compared to controls, supported by confirmatory RT-PCR results. Our findings of consistently lower TOMM40 expression on longitudinal 2-year sampling support its potential role as a diagnostic blood AD biomarker.
    No preview · Article · Sep 2014 · Journal of Alzheimer's disease: JAD
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    ABSTRACT: Objective: The conventional practice of assessing cognitive status and monitoring change over time in older adults using normative values of the Mini-Mental State Exam (MMSE) based on age bands is imprecise. Moreover, population-based normative data on changes in MMSE score over time are scarce and crude because they do not include age- and education-specific norms. This study aims to develop unconditional standards for assessing current cognitive status and conditional standards that take prior MMSE score into account for assessing longitudinal change, with percentile curves as smooth functions of age. Methods: Cross-sectional and longitudinal data of a modified version of the MMSE for 2,026 older Chinese adults from the Singapore Longitudinal Aging Study, aged 55-84, in Singapore were used to estimate quantile regression coefficients and create unconditional standards and conditional standards. Results: We presented MMSE percentile curves as a smooth function of age in education strata, for unconditional and conditional standards, based on quantile regression coefficient estimates. We found the 5th and 10th percentiles were more strongly associated with age and education than were higher percentiles. Model diagnostics demonstrated the accuracy of the standards. Conclusion: The development and use of unconditional and conditional standards should facilitate cognitive assessment in clinical practice and deserve further studies.
    No preview · Article · Aug 2014 · American Journal of Geriatric Psychiatry
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    ABSTRACT: Background: Discordance between patient- and caregiver-reported quality of life (QoL) is well recognized. This study sought to (i) identify predictors of discrepancy between patient- and caregiver-rated QoL amongst community-dwelling persons with mild-to-moderate dementia, and (ii) differentiate between patients who systematically rate their QoL lower versus those who rate their QoL higher relative to their caregiver ratings. Methods: We recruited 165 patient-caregiver dyads with mild-to-moderate dementia. Quality of life in Alzheimer's disease (QoL-AD) scale was administered separately to patients and caregivers. Data on socio-demographics, interpersonal relationship, and disease-related characteristics (cognitive performance, mood, neuropsychiatric symptoms, functional ability, and caregiver burden) were collected. Patient-caregiver dyads were categorized based on whether patient-rated QoL was lower or higher than their respective caregiver ratings. Univariate analyses and multiple regression models were performed to identify predictors of dyadic rating discrepancy. Results: Mean patient-rated QoL was significantly higher than caregiver rating (mean difference: 3.8 ± 7.1, p < 0.001). Majority (111 (67.2%)) of patients had more positive self-perceived QoL (QoL-ADp (QoL-AD self rated by the patient) > QoL-ADc (QoL-AD proxy-rated by a caregiver)), compared with those (44 (26.7%)) with poorer self-perceived QoL (QoL-ADp < QoL-ADc). Patient's education level, depressive symptoms, and severity of neuropsychiatric symptoms predicted magnitude of discrepancy. Depression (OR = 1.17, 95% CI = 1.02-1.35) and being cared for by other relative (non-spouse/adult child; OR = 7.54, 95% CI = 1.07-53.03) predicted poorer self-perceived QoL. Conclusions: Dyadic rating discrepancy in QoL should draw the clinician's attention to patient depression and neuropsychiatric symptoms. Consideration should also be given to nature of patient-caregiver relationship when discordance between patient and caregiver assessments of QoL is observed.
    No preview · Article · Aug 2014 · International Psychogeriatrics
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    Laura Tay · Wee Shiong Lim · Peng Chew Mark Chan · Mei Sian Chong

    Preview · Article · Jul 2014