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Shahul Hameed

Bio: Shahul Hameed is an academic researcher from Singapore General Hospital. The author has contributed to research in topics: Dementia & Hyperintensity. The author has an hindex of 10, co-authored 36 publications receiving 255 citations. Previous affiliations of Shahul Hameed include Nanyang Technological University & National University of Singapore.

Papers
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Journal ArticleDOI
TL;DR: Peripheral TREM2 mRNA levels are higher in AD and are associated with AD-related cognitive deficits and hippocampal atrophy, suggesting that TREM 2 may be a potential non-invasive peripheral biomarker for AD diagnosis.
Abstract: BACKGROUND Variants in triggering receptor expressed on myeloid cells 2 (TREM2) are associated with increased Alzheimer's disease (AD) risk. Recent studies have reported inconsistent peripheral TREM2 mRNA expression levels and relationship with cognitive scores in AD and mild cognitive impairment (MCI). Additionally, no study has examined the association of peripheral TREM2 levels with neuroimaging measures in AD and MCI. OBJECTIVE To determine peripheral TREM2 mRNA levels in AD, amnestic MCI (aMCI) and healthy controls, and the association with cognitive performance and brain structural changes. METHODS We measured peripheral TREM2 mRNA levels in 80 AD, 30 aMCI, and 86 healthy controls using real time polymerase chain reaction. TREM2 levels were correlated with various cognitive performance and brain volumes, correcting for APOE4 status. RESULTS TREM2 mRNA levels were significantly higher in AD compared to controls and aMCI. Levels did not differ between aMCI and controls. Corrected for APOE4, higher TREM2 levels correlated with lower Mini-Mental State Examination, Montreal Cognitive Assessment (MoCA) and episodic memory scores, and lower total grey matter and right hippocampal volumes. Whole-brain voxel-based morphometry analysis found negative association between TREM2 mRNA levels and grey matter volumes in temporal, parietal and frontal regions. AD subjects with MoCA scores ≤20 had higher TREM2 levels correlating with smaller total grey matter, left hippocampal and right hippocampal volumes. CONCLUSION Peripheral TREM2 mRNA levels are higher in AD and are associated with AD-related cognitive deficits and hippocampal atrophy. Our findings suggest that TREM2 may be a potential non-invasive peripheral biomarker for AD diagnosis.

39 citations

Journal ArticleDOI
TL;DR: The clinical, cognitive, and behavioral associations of anosognosia in AD and MCI subjects are investigated to investigate the presence of impaired insight among patients with mild cognitive impairment (MCI).
Abstract: Aims and objective While loss of insight of cognitive deficits is a common phenomenon in patients with Alzheimer's disease (AD), there is a lack of consensus regarding the presence of impaired insight among patients with mild cognitive impairment (MCI). We aim to investigate the clinical, cognitive, and behavioral associations of anosognosia in AD and MCI subjects. Methods A consecutive series of 87 subjects (30 healthy older patients, 21 MCI, and 36 AD) each accompanied by a caregiver, underwent clinical assessment including the evaluation of insight using the Anosognosia Questionnaire for Dementia (AQD). We also separately assessed Intellectual Function (AQD-IF) and Behavior domains of the AQD scale. Regression models were subsequently used to investigate associations of AQD scores with cognitive and other neuropsychiatric symptoms, including depression and apathy. Results Both AD and MCI groups demonstrated significant anosognosia compared with the healthy control group. In the AD group, 55.6% had “Mild Anosognosia,” and 27.8% had “Severe Anosognosia.” In the MCI group, 42.9% showed “Mild Anosognosia,” and 9.5% had “Severe Anosognosia.” Greater levels of AQD-Total and AQD-IF were associated with lower Mini-mental state examination and higher apathy scores in the AD group. In the MCI group, caregiver burden was significantly associated with AQD-Total (p = 0.016) and AQD-IF (p = 0.039). Conclusion The results indicated that anosognosia is common in both AD and MCI patients and associated with cognitive dysfunction and apathy in AD. The findings of this study warrant further research to delineate the mechanisms of anosognosia as it poses a challenge to treatment outcomes. Copyright © 2015 John Wiley & Sons, Ltd.

38 citations

Journal ArticleDOI
TL;DR: Patients with YOD have a high economic burden and YOD patients with Alzheimer's disease, frontotemporal dementia, and vascular dementia had higher cost compared to their elderly counterparts.
Abstract: Background Young onset dementia (YOD) presents in individuals who are economically productive and socially active. While the cost related to dementia in the elderly has been widely studied, the cost related to YOD is largely unknown. Objective To study the economic burden of community dwelling YOD in relation to late onset dementia (LOD) and cost of YOD based on etiology. Methods In this prospective cross-sectional study of 255 patients attending a tertiary neurology center, data on economic burden, clinical features, and caregiver burden were collected using structured financial questionnaire, standard cognitive and neuropsychiatric measures, and Zarit caregiver burden scale. Cost components were grouped into those relating to direct medical costs, direct non-medical costs, and those related to indirect costs. Cost was also categorized based on etiology of YOD. Results The mean age at symptom onset in the YOD and LOD cohort was 57.0 (SD 5.1) and 75.0 (SD 5.9) years, respectively. The median annual cost for patients with YOD was almost twice that of LOD (USD 15,815 versus USD 8,396). Indirect cost contributed heavily to cost related to YOD. Even when grouped by dementia etiology, YOD patients with Alzheimer's disease, frontotemporal dementia (FTD), and vascular dementia had higher cost compared to their elderly counterparts. Young onset FTD had the highest cost. 43.2% of YOD reported loss of employment due to dementia, which was significantly higher than that in LOD (2.4%). Conclusion Patients with YOD have a high economic burden. Young patients with FTD have the highest cost followed by vascular dementia and Alzheimer's disease.

29 citations

Journal ArticleDOI
12 Feb 2020
TL;DR: In this article, the application of approved radiotracers has potential in amyloid-PET brain imaging to detect early Alzheimer's disease (AD) in adults with cognitive impairment and other causes of cognitive decline.
Abstract: Clinical diagnosis of Alzheimer's disease (AD) is based on symptoms; however, the challenge is to diagnose AD at the preclinical stage with the application of biomarkers and initiate early treatment (still not widely available). Currently, cerebrospinal fluid (CSF) amyloid-β 42 (Aβ42) and tau are used in the clinical diagnosis of AD; nevertheless, blood biomarkers (Aβ42 and tau) are less predictive. Amyloid-positron emission tomography (PET) imaging is an advancement in technology that uses approved radioactive diagnostic agents (florbetapir, flutemetamol, or florbetaben) to estimate Aβ neuritic plaque density in adults with cognitive impairment evaluated for AD and other causes of cognitive decline. There is no cure for AD to date-the disease progression cannot be stopped or reversed; approved pharmacological agents (donepezil, galantamine, and rivastigmine; memantine) provide symptomatic treatment. However, the disease-modifying therapies are promising; aducanumab and CAD106 are in phase III trials for the early stages of AD. In conclusion, core CSF biomarkers reflect pathophysiology of AD in the early and late stages; the application of approved radiotracers have potential in amyloid-PET brain imaging to detect early AD.

27 citations

Journal ArticleDOI
TL;DR: The finding suggests that the A673T protective variant is not relevant in the Asian population, and studies in other ethnic populations would clarify whether this variant is specific to specific races/ethnicities.

27 citations


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01 Jan 2020
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

4,408 citations

Journal ArticleDOI
TL;DR: An overview of inflammation in AD is provided and a detailed coverage of a number of microglia‐related signaling mechanisms that have been implicated in AD are reviewed.

1,088 citations

01 Jan 1980

543 citations

Journal ArticleDOI
TL;DR: The results of a consensus meeting about measurement standards and patient characteristics that should be collected in all future stroke recovery trials are presented and a strong case is made for addition of kinematic and kinetic movement quantification.
Abstract: Finding, testing and demonstrating efficacy of new treatments for stroke recovery is a multifaceted challenge. We believe that to advance the field, neurorehabilitation trials need a conceptually rigorous starting framework. An essential first step is to agree on definitions of sensorimotor recovery and on measures consistent with these definitions. Such standardization would allow pooling of participant data across studies and institutions aiding meta-analyses of completed trials, more detailed exploration of recovery profiles of our patients and the generation of new hypotheses. Here, we present the results of a consensus meeting about measurement standards and patient characteristics that we suggest should be collected in all future stroke recovery trials. Recommendations are made considering time post stroke and are aligned with the international classification of functioning and disability. A strong case is made for addition of kinematic and kinetic movement quantification. Further work is being undertaken by our group to form consensus on clinical predictors and pre-stroke clinical data that should be collected, as well as recommendations for additional outcome measurement tools. To improve stroke recovery trials, we urge the research community to consider adopting our recommendations in their trial design.

355 citations