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.

Nutritional Status and Risks of Cognitive Decline and Incident Neurocognitive Disorders: Singapore Longitudinal Ageing Studies.

BACKGROUND: Studies suggest that nutritional interventions using the whole diet approach such as the Mediterranean diet may delay cognitive decline and dementia onset. However, substantial numbers of older adults are non-adherent to any ideally healthy dietary pattern and are at risk of malnutrition. OBJECTIVE: The present study investigated the relationship between global malnutrition risk and onsets of cognitive decline and neurocognitive disorders (NCD), including mild cognitive impairment (MCI) or dementia in community-dwelling older adults. METHODS: Participants aged ≥ 55 years in the Singapore Longitudinal Ageing Studies (SLAS) were assessed at baseline using the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA) and followed up 3-5 years subsequently on cognitive decline (MMSE drop ≥ 2) among 3128 dementia-free individuals, and incident neurocognitive disorders (NCD) among 2640 cognitive normal individuals. RESULTS: Individuals at high nutritional risk score (≥ 3) were more likely to develop cognitive decline (OR=1.42, 95%CI=1.01-1.99) and incident MCI-or-dementia (OR=1.64, 95%CI=1.03-2.59), controlling for age, sex, ethnicity, low education, APOE-e4, hearing loss, physical, social, and mental activities, depressive symptoms, smoking, alcohol, central obesity, hypertension, diabetes, low HDL, high triglyceride, cardiac disease, and stroke. Among ENIGMA component indicators, low albumin at baseline was associated with cognitive decline and incident NCD, and 5 or more drugs used, few fruits/vegetables/milk products daily, and low total cholesterol were associated with incident NCD. CONCLUSION: The ENIGMA measure of global malnutrition risk predicts cognitive decline and incident neurocognitive disorders, suggesting the feasibility of identifying vulnerable subpopulations of older adults for correction of malnutrition risk to prevent neurocognitive disorders.

A systematic review of rescue analgesic strategies in acute exacerbations of primary trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) can have a significant impact on wellbeing and quality of life. Limited data exist for treatments that improve TN pain acutely, within 24 h of administration. This systematic review aims to identify effective treatments that acutely relieve TN exacerbations. METHODS: We searched Medline and Cochrane Central Register of Controlled Trials (CENTRAL) for relevant English language publications. The reference list for all articles was searched for other relevant publications. All studies that satisfied the following PICO criteria were included: (i) Population-adults with acute exacerbation of primary TN symptoms; (ii) Intervention-any medication or intervention with the primary goal of pain relief within 24 h; (iii) Comparator-usual medical care, placebo, sham or active treatment; (iv) Outcome-more than 50% reduction in pain intensity within 24 h of administration. RESULTS: Of 431 studies, 17 studies were identified that reported immediate results of acute treatment in TN. The evidence suggests that the following interventions may be beneficial: local anaesthetic, mainly lidocaine (ophthalmic, nasal or oral mucosa, trigger point injection, i.v. infusion, nerve block); anticonvulsant, phenytoin or fosphenytoin (i.v. infusion); serotonin agonist, sumatriptan (s.c. injection, nasal). Other referenced interventions with very limited evidence include N-methyl-d-aspartate receptor antagonist (magnesium sulphate infusion) and botulinum toxin (trigger point injection). CONCLUSIONS: Several treatment options exist that may provide fast and safe relief of TN. Future studies should report on outcomes within 24 h to improve knowledge of the acute analgesic TN treatments.

Thrombolysis for submassive pulmonary embolism with left ventricular outflow tract obstruction.

The decision to administer thrombolysis in submassive pulmonary embolism is undertaken based on risk stratification to prevent further cardiorespiratory deterioration. Although right ventricular dysfunction has been used to risk stratify haemodynamically stable patients with acute pulmonary embolism, there is still much controversy in the use of thrombolysis for its treatment. The European Society of Cardiology guidelines suggest thrombolysis should be reserved for rescue reperfusion. However, we present a unique case of submassive pulmonary embolism in which transthoracic echocardiography visualised dynamic left ventricular outflow tract obstruction secondary to right ventricular dilatation, which led to the decision to instigate thrombolysis therapy. A 68-year-old man presented with submassive pulmonary embolism with evidence of right ventricular dysfunction but was haemodynamically stable. He was initially commenced on anticoagulation but echocardiography revealed significant right ventricular dilatation and left ventricular outflow tract obstruction, signifying a high risk of impending cardiac arrest. After deliberation, full-dose thrombolysis was administered. Subsequently the patient's symptoms and haemodynamics improved significantly and repeat echocardiography demonstrated that the right ventricular and left ventricular size and function had returned to normal. We suggest echocardiography is used to assess right heart, left heart and outflow dynamics to individualise thrombolysis therapy in patients with submassive pulmonary embolism.

Validity of estimating muscle and fat volume from a single MRI section in older adults with sarcopenia and sarcopenic obesity.

AIM: To determine if there is a correlation between the cross-sectional areas (CSAs) in a single section and the volumes of muscles and fat in the thigh of sarcopenic and sarcopenic obesity (SO) populations using magnetic resonance imaging (MRI), and to assess the correlation between thigh MRI data and patient health status, i.e., normal, obese, sarcopenia, and SO. MATERIALS AND METHODS: One hundred and ninety community-dwelling older adults were recruited and categorised into four subgroups based on Asian established criteria: normal, obese, sarcopenia, and SO. MRI images were acquired and muscles, subcutaneous fat (SF), and intermuscular fat (IMF) were automatically segmented in the thighs. Volumes of muscles and fat were calculated for the middle third of the thigh, while CSAs were assessed using a single section at 50% femur length. RESULTS: Correlation between CSA and volume were significantly high (p<0.001) for all components of muscle (0.907), SF (0.963), and IMF (0.939). Thigh CSA and volume both correlated significantly with a clinical diagnosis of normal, obesity, sarcopenia, and SO (p<0.03). CONCLUSIONS: A single CSA at 50% of femur length yields good estimation of muscle and fat volume in the thighs of older adults and correlates closely with the clinical criteria for sarcopenia and SO. This has the potential to greatly reduce costs, scan time, and post-processing time in clinical practice for the prediction of these conditions.

Depressive Symptoms Increase the Risk of Mild Neurocognitive Disorders among Elderly Chinese.

BACKGROUND: Depression is prevalent among patients with late life neurocognitive disorders but its role as an independent risk factor is not established. We aimed to examine the longitudinal relationship between depression and the incidence of mild neurocognitive disorders (NCD) in a Chinese population. METHODS: We analyzed data from 889 community-living Chinese elderly in the Singapore Longitudinal Aging Study (SLAS) cohort. All subjects were cognitively normal at baseline based on their performance on the Mini-Mental State Examination (MMSE). Depression was defined as total score of 5 or more on the 15-item Geriatric Depression Scale. Incident cases of mild NCD were ascertained at follow up after an average of 45 moths (range: 10-62). Odds ratios (OR) of associations were calculated in logistic regression models that adjusted for potential confounders. RESULTS: A total of 59 mild NCD cases were identified. Increased risk of mild NCD was observed for subjects who had depressive symptom at baseline (OR=2.56, 95%CI 1.17-5.60) after controlling for age, gender, education, hypertension, diabetes mellitus, heart disease, APOE genotype and length of follow-up. The interaction between depression and APOE genotype was not statistically significant. CONCLUSION: Depressive symptom was independently associated with increased risk of mild NCD among Chinese elderly. Effective management of late life depression may potentially reduce incident cases of NCD in the population.

Tea Consumption Reduces the Incidence of Neurocognitive Disorders: Findings from the Singapore Longitudinal Aging Study.

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.

Pain. Part 10: Headaches.

This last in a series of 10 papers aims to provide the dental and medical teams with an update in headache conditions relevant to dentistry and medicine. Headache is the most common presenting symptom for patients presenting to A&E departments. CPD/Clinical Relevance: Most of the dental team take for granted their knowledge and ability to manage acute dental pain. However, the education and preparation in managing patients with headache conditions remains poor. Dentists are in a privileged position to be able to advise their patients about common conditions including headaches.

The Independent Role of Inflammation in Physical Frailty among Older Adults with Mild Cognitive Impairment and Mild-to-Moderate Alzheimer's Disease.

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.

Sex-specific differences in risk factors for sarcopenia amongst community-dwelling older adults.

With considerable variation including potential sex-specific differential rate of skeletal muscle loss, identifying modifiable factors for sarcopenia will be pivotal to guide targeted interventions. This study seeks to identify clinical and biological correlates of sarcopenia in community-dwelling older adults, with emphasis on the role of anabolic and catabolic stimuli, and special reference to gender specificity. In this cross-sectional study involving 200 community-dwelling and functionally independent older adults aged ≥50 years, sarcopenia was defined using the Asian Working Group for Sarcopenia criteria. Comorbidities, cognitive and functional performance, physical activity and nutritional status were routinely assessed. Biochemical parameters included haematological indices, lipid panel, vitamin D level, anabolic hormones [insulin-like growth factor-1 (IGF-1), free testosterone (males only)] and catabolic markers [inflammatory markers (interleukin-6, C-reactive protein) and myostatin]. Multiple logistic regression was performed to identify independent predictors for sarcopenia. Age was associated with sarcopenia in both genders. Malnutrition conferred significantly higher odds for sarcopenia in women (OR = 5.71, 95% CI 1.13-28.84.44, p = 0.035) while higher but acceptable range serum triglyceride was protective in men (OR = 0.05, 95% CI 0.00-0.52, p = 0.012). Higher serum myostatin independently associated with higher odds for sarcopenia in men (OR = 1.11, 95% CI 1.00-1.24, p = 0.041). Serum IGF-1 was significantly lower amongst female sarcopenic subjects, with demonstrable trend for protective effect against sarcopenia in multiple regression models, such that each 1 ng/ml increase in IGF-1 was associated with 1% decline in odds of sarcopenia in women (p = 0.095). Our findings support differential pathophysiological mechanisms for sarcopenia that, if corroborated, may have clinical utility in guiding sex-specific targeted interventions for community-dwelling older adults.

Tea for Alzheimer Prevention.

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.

Stage-Specific Relationship between Frailty and Cognitive Impairment in a Specialist Memory Clinic Setting.

BACKGROUND: It is unclear if the complex relationship between physical frailty and cognition varies across the severity of cognitive impairment. OBJECTIVES: We therefore aimed to explore if there are stage-specific differences in the relationship between frailty and cognitive impairment. DESIGN: Cross-sectional study. SETTING: A specialist Memory Clinic setting. PARTICIPANTS: Mild cognitive impairment (MCI) and mild-moderate Alzheimer's disease (AD) community-dwelling subjects. MEASUREMENTS: We obtained data on demographics, multimorbidity, cognition-related measures, nutrition, neuroimaging measures, muscle mass, Vitamin D level, apolipoprotein - e (APOE) status and physical performance measures. Frailty measures of gait speed, hand grip strength, question on exhausation and weight loss, classified subjects according to the Buchmann criteria into non-frail and frail categories. RESULTS: Forty-five MCI, 64 mild AD and 13 moderate AD subjects (total n=122) were studied. The prevalence of frailty for MCI, mild AD and moderate AD was 35.6%, 21.9% and 46.2% respectively, indicating a u-shaped trend. Significant differences were noted in fatigue, grip strength and gait speed frailty sub-items. Significant correlation of frailty with cognition were noted in mild-moderate AD (Spearman's coefficient 0.26, p<0.05) but not in MCI (0.01, p=0.6). No other differences in multimorbidity, Vitamin D, APOE, nutritional measures, white matter lesions were observed. Sarcopenia interestingly had an inverse stage-specific relationship unlike frailty. CONCLUSIONS: Our results suggest a U-shaped relationship between frailty and cognition, characterized by initial dissociation with cognitive impairment and subsequent convergence at later stages. Future studies incorporating immune markers and endocrine pathways with longitudinal follow-up could potentially elucidate intermediary mechanisms in the frailty cascade.

Ministry of health clinical practice guidelines: dementia.

The Ministry of Health (MOH) has updated the clinical practice guidelines on Dementia to provide doctors and patients in Singapore with evidence-based treatment for dementia. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on Dementia, for the information of readers of the Singapore Medical Journal. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical/2013/cpgmed_dementia_revised.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Diabetic retinopathy in native and non-native Sarawakians--findings from the Diabetic Eye Registry.

This study aims to determine the risk factors associated with diabetic retinopathy (DR) among natives and non-natives Sarawakians who were seen at 3 public hospitals and one health clinic in Sarawak. It is a cross sectional study where data on patients with DM were collected by staff at these healthcare facilities and entered into the web-based Diabetic Eye Registry. Univariate and multivariate analysis was used to determine the association factors for DR. DR was significantly less associated with natives (24.4%) compared to non-native Sarawakians (34.1%) (p < 0.001). The odds of getting DR was higher in patients whose duration of DM was more than 20 years (OR = 2.6), who have renal impairment (OR = 1.7) and non-natives (OR = 1.4).

Severe diabetic papillopathy mimicking non-arteritic anterior ischemic optic neuropathy (NAION) in a young patient.

With the pathophysiology not clearly understood and fewer than 130 cases having been reported in the literature, diabetic papillopathy presents a special challenge to the ophthalmologist. We report a case of a young patient with more than 12 years of type 1 diabetes mellitus (T1DM) on insulin with poor compliance to treatment who presented with sudden bilateral loss of vision. Ocular examination, fluorescence angiography (FA) and systemic signs were conclusive of diabetic papillopathy. His fasting blood sugar level was high and serum glycosylated haemoglobin (HbA1c) indicated a long term fluctuating blood glucose control. His vision initially improved with treatment, but later deteriorated with tight glycemic control.

Amnestic mild cognitive impairment and early Alzheimer's disease in an asian memory clinic - evidence for a clinical spectrum.

OBJECTIVES: To determine if mild cognitive impairment (MCI) represents a continuum of cognitive and functional deficits. METHODS: Clinical data of 164 subjects with no dementia (ND, n = 52), uncertain dementia (n = 69), and mild probable Alzheimer's disease (AD, n = 43) were reviewed. Uncertain dementia patients were classified as pre-MCI (n = 11), early amnestic MCI (e-aMCI, n = 15) and late amnestic MCI (l-aMCI, n = 15). Cognitive assessments [Chinese Mini-Mental State Examination (CMMSE) and a validated neuropsychological battery], functional assessments (Lawton's scale for instrumental activities of daily living) and neuroimaging (ischemic lesions and medial temporal lobe atrophy) were reviewed. RESULTS: ND, aMCI and mild AD subjects demonstrated a significant trend for worsening performance for all cognitive and functional measures (ANOVA, p < 0.05). Pre-MCI subjects performed significantly better than aMCI subjects in all verbal memory domains (p < 0.001), while l-aMCI had worse functional performance (p = 0.007), a trend towards greater depressive symptoms (p = 0.05) and higher medial temporal lobe atrophy scores (p = 0.06). l-aMCI subjects were more likely than either pre-MCI or e-aMCI to progress to dementia over a mean follow-up period of 2.5 years (46.7 vs. 9.1 and 20.0%, respectively). CONCLUSIONS: Clinical delineation of aMCI allows the differentiation of those likely to progress for better correlation to biomarker development.

Diagnostic performance of the Chinese Frontal Assessment Battery in early cognitive impairment in an Asian population.

BACKGROUND: The Frontal Assessment Battery (FAB) has been shown to be useful in evaluating frontal dysfunction. There is a paucity of studies validating cutoffs in the early cognitive impairment. We aim to validate the Chinese FAB in Asian subjects with mild cognitive impairment (MCI) and early dementia. METHODS: Eighty subjects with MCI and mild dementia and 100 cognitively healthy community subjects were studied. ROC analysis was done to determine the Chinese FAB's optimal cutoff scores for age- and education-adjusted subgroups. RESULTS: Chinese FAB scores were significantly lower in early cognitive impairment compared with cognitively normal controls. The optimal cutoff score was 12/13 (sensitivity 92%, specificity 78.7%). A similar cutoff score was obtained following age-adjustment and for subjects with <6 years' education. Of note, the optimal cutoff for subjects with ≥6 years' education was 13/14 (sensitivity 91.8%, specificity 70.3%), an improved diagnostic performance compared to the earlier reported 11/12 cutoff. In comparison, the Mini-Mental Status Examination (MMSE) had lower rule-out accuracy (77% sensitivity, 91.2% specificity). The combination of the Chinese FAB and MMSE was superior to either test in isolation. CONCLUSION: The education-adjusted Chinese FAB has good diagnostic performance, which can supplement the MMSE in early cognitive impairment evaluation with construct differences observed between the Chinese FAB and MMSE.