Cost-benefit and discriminant validity of a stepwise dementia case-finding approach in an Asian older adult community.

Background: Case-finding is a recommended approach for dementia early detection in the community. Aims: To investigate the discriminant validity and cost-effectiveness of a stepwise dementia case-finding approach in a Singaporean older adult community. Methods: The two-phase study was conducted in the community from 2009 to 2015 in Singapore. A total of 3780 participants (age ≥60 years) completed phase I (a brief cognitive screening); 918 completed phase II and were included in the final analysis. In phase I, all participants were administered the Abbreviated Mental Test (AMT) and the Progressive Forgetfulness Question (PFQ). Those who screened positive on either test were invited to phase II, whereby the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and a formal neuropsychological battery were administered, followed by the research diagnosis of no cognitive impairment, cognitive impairment no dementia (CIND)-Mild (≤2 impaired cognitive domains), CIND-Moderate (>2 impaired domains) or dementia. Receiver operating characteristic curve analyses were conducted for the different cognitive instruments. All discriminant indices were calculated, including sensitivity, specificity, positive and negative predictive values (NPV) and accuracy. Cost-effectiveness analysis was conducted by estimating the amount of screening time needed and the number of older adults requiring re-evaluation in two case-finding scenarios, ie, with or without preselection by the PFQ. Results: The stepwise case-finding approach (preselection by the PFQ, then MMSE or MoCA or AMT) showed an excellent NPV (>99%) and accuracy (>86%) for excluding dementia-free cases. Without preselection by the PFQ, screening time for the three cognitive tools were 317.5, 317.5 and 254 hours, with 159, 302 and 175 screen-positive older adults involved in further evaluation. By adopting the stepwise case-finding approach, total screening time were 156.5, 156.5 and 126.2 hours, which decreased by 50.7%, 50.7% and 50.3% as compared with those without preselection. Furthermore, after preselection, only 98, 167 and 145 screen-positive older adults required further evaluation, corresponding to a reduction of 38.4%, 44.7% and 17.1% in the numbers compared with those without preselection. Conclusions: A stepwise approach for dementia case-finding should be implemented in the community to minimise the time and resources needed for large-scale early detection of dementia.

Retinal Vasculature Fractal and Stroke Mortality.

BACKGROUND AND PURPOSE: Fractal analysis is a method of quantifying the branching complexity and density of the retinal vessels. We hypothesized that reduced fractal dimension, signifying a sparser vascular network, is associated with long-term stroke mortality. METHODS: We examined the relationship of fractal dimension and stroke mortality in a prospective, population-based cohort of 3143 participants aged 49 years or older. Fractal dimension was measured from digitized fundus photographs using a computer-automated method. Stroke mortality was documented from Australian National Death Index records. We defined reduced fractal dimension as values in the lowest quartile. RESULTS: Over 12 years, there were 132 (4.2%) stroke-related deaths. Stroke-related mortality was higher in participants with reduced fractal dimension (lowest quartile) compared with the highest quartile (7.7% versus 1.3%, P<0.01). After controlling for age, gender, smoking, blood pressure, history of stroke, and other factors, participants with reduced fractal dimension had higher stroke mortality (hazard ratio, 2.42 [95% CI, 1.15-5.07], lowest versus highest quartile). When modeled as a continuous variable, reduced fractal dimension was associated with increased stroke mortality (multivariable-adjusted hazard ratio, 1.26 [95% CI, 1.06-1.51], per SD decrease). CONCLUSIONS: Reduced retinal vascular fractal dimension is independently associated with 12-year stroke mortality. Reduced fractal dimension may indicate cerebral tissue hypoxia and increased risk of stroke.

Statistical inference for decision curve analysis, with applications to cataract diagnosis.

Statistical learning methods are widely used in medical literature for the purpose of diagnosis or prediction. Conventional accuracy assessment via sensitivity, specificity, and ROC curves does not fully account for clinical utility of a specific model. Decision curve analysis (DCA) becomes a novel complement as it incorporates a clinical judgment of the relative value of benefits (treating a true positive case) and harms (treating a false positive case) associated with prediction models. The preference of a patient or a policy-maker is formulated statistically as the underlying threshold probability, above which the patient would choose to be treated. Net benefit is then calculated for possible threshold probability, which places benefits and harms on the same scale. We consider the inference problems for DCA in this paper. Interval estimation procedure and inference methodology are provided after we derive the relevant asymptotic properties. Our formulation can accommodate the classification problems with multiple categories. We carry out numerical studies to assess the performance of the proposed methods. An eye disease dataset is analyzed to illustrate our proposals.

The NeuroAiD II (MLC901) in vascular cognitive impairment study (NEURITES).

BACKGROUND: A substantial proportion of patients after nondisabling stroke are cognitively impaired compared to age- and education-matched community-dwelling controls. Moreover, poststroke patients who have 'vascular cognitive impairment no dementia' (VCIND) of moderate severity have a high risk of incident dementia, dependency and death. Further studies are urgently needed to demonstrate effective cognition-enhancing therapies in VCIND given the scarcity of evidence-based treatment options. NeuroAiD is a traditional Chinese medicine that has been shown to induce neuroplasticity, promote cell proliferation and stimulate the development of dense axonal and dendritic networks in animal stroke models. NeuroAiD may improve cerebral blood flow and functional recovery after stroke in patients. OBJECTIVE: To investigate the effects and tolerability of NeuroAiD II in patients with VCIND. METHODS: The NeuroAiD II (MLC901) in Vascular Cognitive Impairment Study (NEURITES) is a 24-week, double-blind, randomized, placebo-controlled phase II study of NeuroAiD II in patients with VCIND. The primary outcome is executive function as measured by the Verbal Fluency test. Secondary outcomes include cognitive assessments such as the ADAS-Cog, MoCA, MMSE and Cognitive Battery: activities of daily living as measured by the Alzhei-mer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scale for mild cognitive impairment, behavior as measured by the Neuropsychiatric Inventory, and depression as measured by the Geriatric Depression Scale and the Beck Depression Scale. In addition, there will be novel exploratory outcomes: (a) magnetic resonance imaging of lesion location (structural imaging), structural integrity of white matter pathways (diffusion tensor imaging), neuronal function (resting studies) and perfusion (arterial spin labeling and MR angiography), and (b) retinal and optic nerve imaging. Safety and tolerability will be assessed using adverse events, laboratory tests and vital signs. CONCLUSIONS: NEURITES has the potential to set new standards for the systematic evaluation of Asian traditional medicine for integration into standard medicine practice and establishing a novel therapeutic approach for improving cognition after stroke.

Dietary factors, myopia, and axial dimensions in children.

PURPOSE: To evaluate the possible associations between dietary factors and myopia. DESIGN: Cross-sectional study. PARTICIPANTS: Eight hundred fifty-one Chinese schoolchildren from the Singapore Cohort Study of Risk Factors for Myopia. METHODS: Diet was assessed using a semiquantitative food-frequency questionnaire. Spherical equivalent (SE) refraction was assessed with an autorefractometer, and axial length (AL) by contact ultrasound A-scan biometry. MAIN OUTCOME MEASURES: Myopia was defined as SE< or =-0.5 diopters (D). Spherical equivalent and AL were analyzed by quartile groups. RESULTS: The mean age (+/-standard deviation) was 12.81+/-0.83 years, approximately half were male (422 children [49.6%]), and 653 (73.8%) children had myopia. In multivariate models, AL was longest in the highest quartile group of total cholesterol intake compared with the lowest (adjusted mean [95% confidence interval], 24.66 [24.62-24.71] mm vs. 24.32 [24.27-24.36] mm; P = 0.026, for trend) and was longest in the highest quartile group of saturated fat intake compared with the lowest (24.65 [24.60-24.70] vs. 24.36 [24.32-24.41] mm; P = 0.039, for trend). None of the nutrients was associated with SE or a diagnosis of myopia. CONCLUSIONS: Higher saturated fat and cholesterol intake are associated with longer AL in otherwise healthy Singapore Chinese schoolchildren.

Retinal arteriolar narrowing and left ventricular hypertrophy in African Americans. the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Whether microvascular disease contributes to the development of left ventricular hypertrophy (LVH) is unclear. We examined the relationship of retinal microvascular signs with LVH in an African-American population. METHODS: A population-based, cross-sectional study of 1,439 middle-aged African-American participants in Jackson, Mississippi. A retinal photograph of one randomly selected eye was obtained and graded for presence of retinal microvascular signs (focal arteriolar narrowing, arterio-venous (AV) nicking, and retinopathy) according to standardized protocols. Retinal vessel diameter was measured from a computer-assisted technique to define generalized arteriolar narrowing. LVH was defined from standardized echocardiography. RESULTS: In age and gender-adjusted models, retinal microvascular signs (except non-diabetic retinopathy) were significantly associated with LVH, with an odds ratio (OR) of 1.64 (95% confidence interval (CI) 1.29-2.09) for generalized arteriolar narrowing, OR 1.82 (95% CI 1.33-2.50) for focal arteriolar narrowing, and OR 1.35 (95% CI 1.02-1.79) for AV nicking. With further adjustment for cardiovascular (serum total cholesterol, fasting glucose, diabetes, diabetes duration, smoking, body mass index (BMI), waist-to-hip ratio, and exercise level) and hypertension-related factors (mean arterial blood pressure (MABP) at the time of retinal photography and antihypertensive medication use), associations were attenuated but remained significant for generalized and focal arteriolar narrowing, with OR 1.35 (95% CI 1.02-1.78) and OR 1.66 (95% CI 1.16-2.38), respectively. CONCLUSIONS: Middle-aged African Americans with generalized and focal retinal arteriolar narrowing were more likely to have LVH. This association was explained only partly by cardiovascular risk factors and hypertension.

A pilot study of lens extraction in the management of acute primary angle-closure glaucoma.

PURPOSE: To describe a pilot study of lens extraction in the management of acute primary angle-closure glaucoma (APACG) in Chinese patients. DESIGN: Interventional case series. METHODS: A prospective case series of patients presented with APACG at a tertiary eye hospital in Xiamen, China. All the patients had intensive medical treatment followed by immediate phacoemulsification and posterior chamber intraocular lens implantation under topical anesthesia. RESULTS: There were 18 patients who were seen with APACG who had phacoemulsification and posterior chamber intraocular lens implantation under topical anesthesia. There was a 9.0-mm Hg drop in mean preoperative and first day postoperative intraocular pressure (22.8 vs 13.8 mm Hg, P =.012) and a 10.2-mm Hg drop in mean preoperative and seventh-day postoperative intraocular pressure (22.8 vs 13.2 mm Hg, P =.002). CONCLUSIONS: This pilot study indicates that phacoemulsification and posterior chamber intraocular lens implantation may be useful in the treatment of primary acute angle-closure glaucoma in Chinese patients. Further study with longer follow-up is needed.