Russell J. Chander

Bio: Russell J. Chander is an academic researcher from University of New South Wales. The author has contributed to research in topics: Hyperintensity & Cognitive decline. The author has an hindex of 16, co-authored 40 publications receiving 601 citations. Previous affiliations of Russell J. Chander include Tan Tock Seng Hospital.

Profile of and risk factors for poststroke cognitive impairment in diverse ethnoregional groups

Abstract: Objective To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. Methods We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. Results In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. Conclusions This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies.

O4-03-04: profile of and risk factors for post-stroke cognitive impairment in diverse ethno-regional groups

Abstract: Objective To address the variability in prevalence estimates and inconsistencies in potential risk factors for poststroke cognitive impairment (PSCI) using a standardized approach and individual participant data (IPD) from international cohorts in the Stroke and Cognition Consortium (STROKOG) consortium. Methods We harmonized data from 13 studies based in 8 countries. Neuropsychological test scores 2 to 6 months after stroke or TIA and appropriate normative data were used to calculate standardized cognitive domain scores. Domain-specific impairment was based on percentile cutoffs from normative groups, and associations between domain scores and risk factors were examined with 1-stage IPD meta-analysis. Results In a combined sample of 3,146 participants admitted to hospital for stroke (97%) or TIA (3%), 44% were impaired in global cognition and 30% to 35% were impaired in individual domains 2 to 6 months after the index event. Diabetes mellitus and a history of stroke were strongly associated with poorer cognitive function after covariate adjustments; hypertension, smoking, and atrial fibrillation had weaker domain-specific associations. While there were no significant differences in domain impairment among ethnoracial groups, some interethnic differences were found in the effects of risk factors on cognition. Conclusions This study confirms the high prevalence of PSCI in diverse populations, highlights common risk factors, in particular diabetes mellitus, and points to ethnoracial differences that warrant attention in the development of prevention strategies. From the Centre for Healthy Brain Ageing (J.W.L., J.D.C., R.J.C., H.B., D.M.L., N.A.K., P.S.S.), University of New South Wales, Sydney, Australia; Department of Neurology and Laboratory of Functional Neurosciences (O.G., M.B., M.R.), University Hospital of Amiens, France; Clinical Neurosciences (H.J., S.M., T.E.), Neurology, University of Helsinki and Helsinki University Hospital, Finland; Department of Internal Medicine (S.M.), Gerontology and Geriatrics Section, and Department of Cardiology (J.W.J.), Leiden University Medical Center, the Netherlands; Department of Neurology (S.M., B.S.), Feinberg School of Medicine, Northwestern University, Chicago, IL; Department of Neurology (H.-J.B.), Seoul National University School of Medicine, Seoul National University Bundang Hospital, Seongnam; Department of Neurology (J.-S.L., B.-C.L.), Hallym University Sacred Heart Hospital, Anyang, Republic of Korea; Department of Psychiatry and Neuropsychology (S.K., E.D.), School for Mental Health and Neuroscience, Alzheimer Center Limburg, Maastricht University; Department of Neurology (J.S.), Cardiovascular Research Institute Maastricht,MaastrichtUniversityMedicalCenter, theNetherlands;MemoryAgingandCognitionCentre (C.C., X.X., E.J.C.),DepartmentofPharmacology, YongLooLinSchoolofMedicine,National University of Singapore; Centre for Population Health Sciences (X.X.), Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Neuroscience and Ageing Research Unit (R.O.A., A.O.), Institute for Advanced Medical Research and Training, and Department of Medicine (R.O.A.), College of Medicine, University of Ibadan, Nigeria; Institute of Neuroscience (R.N.K.), Newcastle University, Newcastle Upon Tyne, UK; Peninsula Clinical School (V.K.S., C.M.), Central Clinical School, Monash University; Department of Aged Care (C.M.), Alfred Health, Melbourne, Australia; National Neuroscience Institute (N.K., R.J.C.); Duke-NUSMedical School (N.K.), Singapore; Dementia Collaborative ResearchCentre (H.B., P.S.S.), University of NewSouthWales, Sydney, Australia; and University of Lille (R.B., S.B., H.H.), Inserm, CHU Lille, U1171-Degenerative & Vascular Cognitive Disorders, France. Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. STROKOG collaboration coinvestigators are listed in Appendix 2 at the end of the article. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. e2257 While poststroke cognitive impairment (PSCI) is mild in many stroke survivors, numerous studies have reported a prevalence of dementia in poststroke cases that varies from 7.4% in a population-based study of first stroke to 41.3% in hospital-based cases of recurrent stroke. The prevalence may differ by geographic region, diagnostic criteria, and methods of assessment. Because the severity of cognitive impairment in poststroke patients is on a continuum, however, it is arguably more meaningful to use a standardized continuous measure to examine cognitive impairment rather than the diagnosis of dementia. Because of the heterogeneity of stroke and its effects on cerebral function, the cognitive profile of poststroke dementia is understandably complex. There is evidence that some cognitive domains, in particular complex attention, working memory, and frontal executive function, are affected early in vascular dementia. Poststroke dementia, however, is also associated with language and visuospatial dysfunction, even though individuals with severe language impairment are often excluded from detailed investigations. In addition, studies of cognitive profile have largely been conducted in white, non-Hispanic populations, and it is uncertain whether the same pattern is seen in Asian and African populations. The clinical determinants of PSCI remain incompletely understood. While older age and low levels of education have consistently emerged as risk factors, various other putative risk factors have been inconsistently reported, including risk factors for cerebrovascular disease (e.g., hypertension, diabetes mellitus, atrial fibrillation [AF], smoking), prior pathology (e.g., previous stroke, Alzheimer disease), APOE genotype, stroke features, and lesion characteristics. The variability of the findings has prevented a consensus from being reached on the most relevant factors in predicting the development of poststroke dementia. The Stroke and Cognition Consortium (STROKOG), an international consortium of studies of cognitive decline and dementia after stroke or TIA, offers an opportunity to address the inconsistencies in prevalence estimates and potential risk factors for PSCI. This article presents a comprehensive profile of the cognitive performance of patients 2 to 6 months after stroke or TIA and explores the associations between a variety of risk factors and impairment in cognitive function. We hypothesized that the prevalence of Glossary AF = atrial fibrillation; CHF = congestive heart failure; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; IPD = individual participant data; MI = myocardial infarction; NEMESIS = North East Melbourne Stroke Incidence Study; PROSPER = Prospective Study of Pravastatin in the Elderly at Risk; PSCI = poststroke cognitive impairment; SAM = Helsinki Stroke Aging Memory Study; STROKDEM = Study of Factors Influencing Post-Stroke Dementia; STROKOG = Stroke and Cognition Consortium. e2258 Neurology | Volume 93, Number 24 | December 10, 2019 Neurology.org/N PSCI will be high across different geographical regions but will vary across different ethnoracial groups. We also hypothesized that PSCI affects different cognitive domains equally and that vascular risk factors for stroke are also risk factors for PSCI independently of the occurrence of stroke.

Cognitive decline in Parkinson disease

Abstract: Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition - or even reversal to normal cognition - is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*e4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

Current state of Alzheimer's fluid biomarkers.

Abstract: Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, α-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.

Vascular cognitive impairment.

Abstract: The term vascular cognitive impairment (VCI) was introduced around the start of the new millennium and refers to the contribution of vascular pathology to any severity of cognitive impairment, ranging from subjective cognitive decline and mild cognitive impairment to dementia. Although vascular pathology is common in elderly individuals with cognitive decline, pure vascular dementia (that is, dementia caused solely by vascular pathology) is uncommon. Indeed, most patients with vascular dementia also have other types of pathology, the most common of which is Alzheimer disease (specifically, the diffuse accumulation of amyloid-β plaques and neurofibrillary tangles composed of tau). At present, the main treatment for VCI is prevention by treating vascular diseases and other risk factors for VCI, such as hypertension and diabetes mellitus. Despite the current paucity of disease-modifying pharmacological treatments, we foresee that eventually, we might be able to target specific brain diseases to prevent cognitive decline and dementia.