Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Alzheimer Disease: HELP
Articles by Kok Pin Ng
Based on 22 articles published since 2010
(Why 22 articles?)
||||

Between 2010 and 2020, K. P. Ng wrote the following 22 articles about Alzheimer Disease.
 
+ Citations + Abstracts
1 Review Brain Metabolic Dysfunction in Early Neuropsychiatric Symptoms of Dementia. 2019

Ng, Kok Pin / Chiew, Hui Jin / Rosa-Neto, Pedro / Kandiah, Nagaendran / Ismail, Zahinoor / Gauthier, Serge. ·Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · The McGill University Research Centre for Studies in Aging, Montreal, QC, Canada. · Duke-NUS Medical School, Singapore, Singapore. · Departments of Psychiatry, Clinical Neurosciences, and Community Health Sciences, Hotchkiss Brain Institute and O'Brien Institute for Public Health, University of Calgary, Calgary, AB, Canada. ·Front Pharmacol · Pubmed #31824321.

ABSTRACT: Neuropsychiatric symptoms (NPS) including behavioral and psychiatric symptoms are common in the dementia stages of Alzheimer's disease (AD) and are associated with poorer outcomes in cognition, functional states, quality of life, and accelerated progression to severe dementia or death. NPS are also increasingly observed in the mild cognitive impairment stage of AD and may predict incipient dementia. As such, there is an emerging conceptual framework, which support NPS as early non-cognitive symptoms of dementia. [

2 Review Impact of the biological definition of Alzheimer's disease using amyloid, tau and neurodegeneration (ATN): what about the role of vascular changes, inflammation, Lewy body pathology? 2018

Gauthier, S / Zhang, H / Ng, K P / Pascoal, T A / Rosa-Neto, P. ·McGill Center for Studies in Aging, Douglas Mental Health Research Institute, Montreal, Canada. · 2Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. · grid.452206.7 · 3Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · 0000 0004 0636 696X · grid.276809.2 ·Transl Neurodegener · Pubmed #29876101.

ABSTRACT: Background: The NIA-AA research framework proposes a biological definition of Alzheimer's disease, where asymptomatic persons with amyloid deposition would be considered as having this disease prior to symptoms. Discussion: Notwithstanding the fact that amyloid deposition in isolation is not associated with dementia, even the combined association of amyloid and tau pathology does not inevitably need to dementia over age 65. Other pathological factors may play a leading or an accelerating role in age-associated cognitive decline, including vascular small vessel disease, neuroinflammation and Lewy Body pathology. Conclusion: Research should aim at understanding the interaction between all these factors, rather than focusing on them individually. Hopefully this will lead to a personalized approach to the prevention of brain aging, based on individual biological, genetic and cognitive profiles.

3 Review Targeting Alzheimer's Disease at the Right Time and the Right Place: Validation of a Personalized Approach to Diagnosis and Treatment. 2018

Gauthier, Serge / Ng, Kok Pin / Pascoal, Tharick A / Zhang, Hua / Rosa-Neto, Pedro. ·McGill Center for Studies in Aging, Douglas Mental Health Research Institute, Montreal, Canada. · Department of Neurology, National Neuroscience Institute, Singapore. · Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. ·J Alzheimers Dis · Pubmed #29504543.

ABSTRACT: Cautious optimism is appropriate for a near future (five years) time frame for a number of drugs acting on the different pathophysiological components of Alzheimer's disease (amyloid deposition, tau hyperphosphorylation, neuroinflammation, vascular changes, to name the most important known so far). Since the relative weight of these components will be different between individuals and will even change over time for each individual, a 'one drug fit for all' approach is no longer defensible. Precision medicine using biomarkers in the diagnosis and treatment of Alzheimer's disease is the new strategy.

4 Review Is ApoE ɛ 4 a good biomarker for amyloid pathology in late onset Alzheimer's disease? 2016

Ba, Maowen / Kong, Min / Li, Xiaofeng / Ng, Kok Pin / Rosa-Neto, Pedro / Gauthier, Serge. ·Department of Neurology, Yuhuangding Hospital Affiliated to Qingdao Medical University, Qingdao, Shandong 264000 People's Republic of China. · McGill Centre for Studies in Aging, McGill University, Douglas Institute, 6825 Lasalle Boul, Montreal, QC H4H 1R3 Canada. · Department of Neurology, Yantaishan Hospital, Yantai City, Shandong 264000 People's Republic of China. · Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010 People's Republic of China. · Department of Neurology, National Neuroscience Institute Singapore, Singapore, Singapore. ·Transl Neurodegener · Pubmed #27891223.

ABSTRACT: Amyloid plaques are pathological hallmarks of Alzheimer's Disease (AD) and biomarkers such as cerebrospinal fluid (CSF) β-amyloid 1-42 (Aβ1-42) and amyloid positron emission tomographic (PET) imaging are important in diagnosing amyloid pathology in vivo. ɛ4 allele of the Apolipoprotein E gene (ApoE ɛ 4), which is a major genetic risk factor for late onset AD, is an important genetic biomarker for AD pathophysiology. It has been shown that ApoE ɛ 4 is involved in Aβ deposition and formation of amyloid plaques. Studies have suggested the utility of peripheral blood ApoE ɛ 4 in AD diagnosis and risk assessment. However it is still a matter of debate whether ApoE ɛ 4 status would improve prediction of amyloid pathology and represent a cost-effective alternative to amyloid PET or CSF Aβ in resource-limited settings in late onset AD. Recent research suggest that the mean prevalence of PET amyloid-positivity is 95% in ApoE ɛ 4-positive AD patients. This short review aims to provide an updated information on the relationship between ApoE ɛ 4 and amyloid biomarkers.

5 Article Identification of novel candidate autoantibodies in Alzheimer's disease. 2020

Wang, Brian Zhiyang / Zailan, Fatin Zahra / Wong, Benjamin Yi Xin / Ng, Kok Pin / Kandiah, Nagaendran. ·Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · Duke-NUS Graduate Medical School, Singapore, Singapore. · NTU-Imperial Lee Kong Chian School of Medicine, Singapore, Singapore. ·Eur J Neurol · Pubmed #32356904.

ABSTRACT: BACKGROUND AND PURPOSE: Accumulated failures in Alzheimer's disease (AD) clinical trials have highlighted an urgent need to identify additional biomarkers involved in AD. Recently, mounting evidence reported that autoantibodies are ubiquitous in human sera. However, whether autoantibodies are upregulated in amyloid-tau biomarker confirmed AD is unknown. METHODS: Forty subjects with mild dementia (CDR=1) were stratified into AD (N=16) and non-AD (N=24) groups according to their CSF levels of tau and Aβ RESULTS: All controls and samples passed the QC criteria and were further used for biomarker analysis. Six autoantibodies with elevated responses to the following autoantigens were found exclusively in the AD group: NAP1L3 (31.3%, 5/16 subjects), MAP4, PANK3, PIK3R1, PTP4A1, and SOX15 (all 18.8%, 3/16 subjects). CONCLUSION: While some identified autoantigens are linked to AD and cognitive dysfunction, the increased autoantibody levels have not been reported in AD. Autoantibodies may provide deeper insights into the pathogenesis of AD and serve as diagnostic biomarkers; their corresponding antigens can be further studied to assess their potential as therapeutic targets.

6 Article Suicidal ideation is common in autosomal dominant Alzheimer's disease at-risk persons. 2020

Ng, Kok Pin / Richard-Devantoy, Stéphane / Bertrand, Josie-Anne / Jiang, Lai / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Therriault, Joseph / Yatawara, Chathuri / Kandiah, Nagaendran / Greenwood, Celia M T / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous861181. ·Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Québec, Canada. · Department of Neurology, National Neuroscience Institute, Singapore. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Québec, Canada. · Department of Psychiatry & Douglas Mental Health University Institute, McGill Group for Suicide Studies, McGill University, Québec, Montréal, Canada. · CISSS des Laurentides, Quebec, Canada. · Douglas Research Center, Douglas Mental Health University Institute, Québec, Canada. · Lady Davis Institute, McGill University, Québec, Canada. · Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Québec, Canada. ·Int J Geriatr Psychiatry · Pubmed #31642105.

ABSTRACT: OBJECTIVES: To study the frequency of suicidal ideation and its association with clinical and neurobiological correlates among cognitively intact autosomal dominant Alzheimer's disease (ADAD) at-risk individuals. METHODS/DESIGN: In a cross-sectional study of 183 ADAD at-risk individuals (91 mutation carriers and 92 noncarriers), we compared the frequency of suicidal ideation among carriers and noncarriers. Linear mixed-effects models with family-level random effects evaluated the relationships between geriatric depression scale (GDS), neuropsychiatric inventory-questionnaire (NPI-Q), and suicidal ideation scores among all ADAD at-risk individuals. An interaction term was added to the regression models to evaluate the interactions of suicidal ideation and mutation status on neuropsychiatric symptoms. RESULTS: Twenty-six (14.20%) ADAD at-risk individuals (13 [14.28%] carriers and 13 [14.13%] noncarriers) had suicidal ideation. The frequency of suicidal ideation did not differ between carriers and noncarriers. Suicidal ideation was associated with higher GDS among all ADAD at-risk individuals. When stratified into mutation carrier status, noncarriers with suicidal ideation had higher GDS than carriers. There was no statistically significant association between suicidal ideation and NPI-Q among ADAD at-risk individuals. Awareness of mutation status, neuropsychological performances, and cerebrospinal fluid AD biomarkers were not associated with suicidal ideation among carriers and noncarriers. CONCLUSIONS: Suicidal ideation is common among cognitively intact ADAD at-risk individuals. While ADAD at-risk individuals with suicidal ideation have greater depressive symptoms, noncarriers with suicidal ideation have higher GDS scores than carriers. Interestingly, awareness of the mutation status was not associated with suicidal ideation in our study. Early identification of suicidal thoughts can facilitate timely interventions to prevent suicidal behaviours. Keywords autosomal dominant Alzheimer's diseasedominantly inherited Alzheimer's networkneuropsychiatric symptomssuicidal ideation.

7 Article Construct validity of the Visual Cognitive Assessment Test (VCAT)-a cross-cultural language-neutral cognitive screening tool. 2020

Low, Audrey / Lim, Levinia / Lim, Linda / Wong, Benjamin / Silva, Eveline / Ng, Kok Pin / Kandiah, Nagaendran. ·Department of Neurology, National Neuroscience Institute, Singapore. · Duke-NUS, Singapore. ·Int Psychogeriatr · Pubmed #31111797.

ABSTRACT: BACKGROUND: The Visual Cognitive Assessment Test (VCAT) is a language-neutral cognitive screening tool designed for use in culturally diverse populations without the need for translations or adaptations. While it has been established to be language-neutral, the VCAT's construct validity has not been investigated. METHODS: 471 participants were recruited, comprising 233 healthy comparisons, 117 mild cognitive impairment (MCI), and 121 mild Alzheimer's disease (AD) patients. VCAT and domain-specific neuropsychological tests were administered in the same sitting. Construct validity was assessed by analyzing domain-specific associations between the VCAT and well-established cognitive assessments. Reliability (internal consistency) was measured by Cronbach's alpha. Diagnostic ability (area under the curve) and recommended cutoffs were determined by receiver operating characteristic (ROC) analysis. RESULTS: The VCAT and its subdomains demonstrated good construct validity in terms of both convergent and divergent validity and good internal consistency (α = .74). ROC analysis found that the VCAT was on par with the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at distinguishing between healthy comparisons, MCI, and mild AD. Consistent with previous studies, VCAT scores were not affected by language of administration or ethnicity in our cohort. Findings suggest the following cutoffs: Dementia 0-19, MCI 20-24, Normal 25-30. CONCLUSION: This study established the construct validity of the VCAT, which is vital to ensure its subdomains effectively measure the cognitive processes they were designed to. The VCAT is capable of detecting early cognitive impairments and allows for meaningful cross-cultural comparisons, especially useful for international collaborations and clinical trials, and for clinical use in diverse multiethnic populations.

8 Article Association of Asymmetrical White Matter Hyperintensities and Apolipoprotein E4 on Cognitive Impairment. 2019

Low, Audrey / Ng, Kok Pin / Chander, Russell Jude / Wong, Benjamin / Kandiah, Nagaendran. ·Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · School of Psychiatry, University of New South Wales, Sydney, Australia. · Duke-NUS, Singapore, Singapore. ·J Alzheimers Dis · Pubmed #31306121.

ABSTRACT: BACKGROUND: Asymmetrical patterns of cerebral damage have been widely observed in a range of neurodegenerative diseases, including Alzheimer's disease (AD). OBJECTIVE: To elucidate the clinical associations of asymmetrical white matter hyperintensities (WMH) in mild cognitive impairment (MCI) and AD. METHODS: Regional WMH asymmetry of 340 participants (90 healthy controls, 132 MCI, 118 AD) was calculated as the difference in normalized hemispheric WMH volume (WMH/ICV) adjusted for structural brain asymmetry of respective lobar regions and total WMH. WMH asymmetry was analyzed in relation to disease classification, cognition, and APOE4 status using ANCOVA and multiple regression analysis, controlling for gender, age, ethnicity, and correcting for multiple comparisons using Bonferroni correction. Moderation analysis examined interaction effects of APOE4 on associations between cognition and WMH asymmetry. RESULTS: Greater left-dominant occipital WMH asymmetry was observed in AD, compared to healthy controls and MCI, and was associated with poorer global cognition, memory, language, and executive functions among cognitively impaired participants (MCI and AD). Cognitively impaired APOE4 carriers displayed greater left-dominant WMH asymmetry in the whole brain and frontal lobe, compared to non-carriers. Importantly, effects were independent of structural brain asymmetry, global cerebral atrophy, and overall WMH burden. Moderation analysis demonstrated associations between left-dominant WMH asymmetry and cognition in cognitively impaired APOE4 non-carriers, but not APOE4 carriers. CONCLUSION: Leftward asymmetry of WMH may be more pathological in nature, compared to symmetrical WMH. Furthermore, the detrimental effects of WMH asymmetry was more relevant in APOE4-negative cognitive impairment, compared to APOE4-positive which may be driven primarily by AD pathology.

9 Article Rostral-Caudal Hippocampal Functional Convergence Is Reduced Across the Alzheimer's Disease Spectrum. 2019

Therriault, Joseph / Wang, S / Mathotaarachchi, S / Pascoal, Tharick A / Parent, M / Beaudry, T / Shin, M / Al, Benedet / Kang, M S / Ng, K P / Dansereau, C / Park, M T M / Fonov, V / Carbonell, F / Zimmer, E / Chakravarty, M Mallar / Bellec, P / Gauthier, S / Rosa-Neto, P / Anonymous2081152. ·McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Montreal, Canada. joseph.therriault1@gmail.com. · Douglas Mental Health University Institute, Montreal, Canada. joseph.therriault1@gmail.com. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Douglas Hospital, McGill University, 6875 La Salle Blvd - FBC room 3149, Montreal, QC, H4H 1R3, Canada. joseph.therriault1@gmail.com. · McGill University Research Centre for Studies in Aging, Douglas Mental Health University Institute, Montreal, Canada. · Douglas Mental Health University Institute, Montreal, Canada. · Institut universitaire de gériatrie de Montréal, Université de Montréal, Montreal, Canada. · McConnell Brain Imaging Centre, Montreal Neurological Institute, Montreal, Canada. · Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil. · Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. ·Mol Neurobiol · Pubmed #31230260.

ABSTRACT: Beginning in the early stages of Alzheimer's disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a metric of the overlap between the rostral and caudal hippocampal functional networks, across the clinical spectrum of AD. We predicted a decline in rostral-caudal hippocampal convergence in the early stages of the disease. Using fMRI, we generated resting-state hippocampal functional networks across 56 controls, 48 early MCI (EMCI), 35 late MCI (LMCI), and 31 AD patients from the Alzheimer's Disease Neuroimaging Initiative cohort. For each diagnostic group, we performed a conjunction analysis and compared the rostral and caudal hippocampal network changes using a mixed effects linear model to estimate the convergence and differences between these networks, respectively. The conjunction analysis showed a reduction of rostral-caudal hippocampal convergence strength from early MCI to AD, independent of hippocampal atrophy. Our results demonstrate a parallel between the functional convergence within the hippocampus and disease stage, which is independent of brain atrophy. These findings support the concept that network convergence might contribute as a biomarker for connectivity dysfunction in early stages of AD.

10 Article Mechanisms Linking White Matter Lesions, Tract Integrity, and Depression in Alzheimer Disease. 2019

Yatawara, Chathuri / Lee, Daryl / Ng, Kok Pin / Chander, Russell / Ng, Debby / Ji, Fang / Shim, Hee Youn / Hilal, Saima / Venketasubramanian, Narayanaswamy / Chen, Christopher / Zhou, Juan / Kandiah, Nagaendran. ·Department of Neurology (CY, DL, KPN, RC, DN, NK), National Neuroscience Institute, Singapore, Singapore. · Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program (FJ, HYS, JZ, NK), Duke-NUS Medical School, Singapore. · National University Health System (SH, CC), Memory Aging & Cognition Centre, Singapore. · Raffles Neuroscience Centre (NV), Raffles Hospital Singapore, Singapore. · Department of Neurology (CY, DL, KPN, RC, DN, NK), National Neuroscience Institute, Singapore, Singapore; Center for Cognitive Neuroscience, Neuroscience and Behavioral Disorders Program (FJ, HYS, JZ, NK), Duke-NUS Medical School, Singapore. Electronic address: Nagaendran.Kandiah@singhealth.com.sg. ·Am J Geriatr Psychiatry · Pubmed #31109898.

ABSTRACT: OBJECTIVE: Late-life depression involves the disconnection of white matter tracts that regulate mood. A pathogenic link between poor tract integrity and depressive symptoms is believed to be white matter lesions (WML), however the mechanisms linking tract integrity, WML, and depression remains unexplored. The authors sought to identify whether the association between reduced tract integrity and depressive symptoms is mediated by WML in patients with Alzheimer disease (AD), and whether individual characteristics moderate this effect. METHODS: This was a cross-sectional study in a tertiary memory clinic. A total of 91 patients with mild AD and 79 healthy elderly, comparable in depressive symptoms, white matter hyperintensities (WMH) volume, cardiovascular risk, age, and sex were chosen. Tract integrity was assessed using diffusion tensor imaging, WML were indexed as WMH, measured using fluid-attenuation inversion recovery imaging, and depressive symptoms were measured with the informant-based Geriatric Depression Scale. RESULTS: In patients with mild AD, reduced tract integrity in right hemispheric cortical-subcortical tracts and the genu of the corpus callosum was moderately associated with depressive symptoms. This association was fully mediated by WML. Moderation analysis indicated that old age strengthened the association between all tracts and depressive symptoms, as mediated by WML. In cognitively healthy elderly, neither tracts nor WML were related to depressive symptoms. CONCLUSION: Reduced tract integrity may be important but not sufficient for the manifestation of depressive symptoms in mild AD. Instead, WML may drive the pathogenic link between reduced tract integrity and depressive symptoms.

11 Article The combination of apolipoprotein E4, age and Alzheimer's Disease Assessment Scale - Cognitive Subscale improves the prediction of amyloid positron emission tomography status in clinically diagnosed mild cognitive impairment. 2019

Ba, M / Ng, K P / Gao, X / Kong, M / Guan, L / Yu, L / Anonymous13201195. ·Department of Neurology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. · Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · Department of Neurology, Yantaishan Hospital, Yantai City, China. ·Eur J Neurol · Pubmed #30561868.

ABSTRACT: BACKGROUND AND PURPOSE: Randomized clinical trials involving anti-amyloid interventions focus on the early stages of Alzheimer's disease (AD) with proven amyloid pathology, using amyloid positron emission tomography (amyloid-PET) imaging or cerebrospinal fluid analysis. However, these investigations are either expensive or invasive and are not readily available in resource-limited centres. Hence, the identification of cost-effective clinical alternatives to amyloid-PET is highly desirable. This study aimed to investigate the accuracy of combined clinical markers in predicting amyloid-PET status in mild cognitive impairment (MCI) individuals. METHODS: In all, 406 MCI participants from the Alzheimer's Disease Neuroimaging Initiative database were dichotomized into amyloid-PET(+) and amyloid-PET(-) using a cut-off of >1.11. The accuracies of single clinical markers [apolipoprotein E4 (ApoE4) genotype, demographics, cognitive measures and cerebrospinal fluid analysis] in predicting amyloid-PET status were evaluated using receiver operating characteristic curve analysis. A logistic regression model was then used to determine the optimal model with combined clinical markers to predict amyloid-PET status. RESULTS: Cerebrospinal fluid amyloid-β (Aβ) showed the best predictive accuracy of amyloid-PET status [area under the curve (AUC) = 0.927]. Whilst ApoE4 genotype (AUC = 0.737) and Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) 13 (AUC = 0.724) independently discriminated amyloid-PET(+) and amyloid-PET(-) MCI individuals, the combination of clinical markers (ApoE4 carrier, age >60 years and ADAS-Cog 13 > 13.5) improved the predictive accuracy of amyloid-PET status (AUC = 0.827, P < 0.001). CONCLUSIONS: Cerebrospinal fluid Aβ, which is an invasive procedure, is most accurate in predicting amyloid-PET status in MCI individuals. The combination of ApoE4, age and ADAS-Cog 13 also accurately predicts amyloid-PET status. As this combination of clinical markers is cheap, non-invasive and readily available, it offers an attractive surrogate assessment for amyloid status amongst MCI individuals in resource-limited settings.

12 Article Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer's disease. 2018

Zhang, Hua / Ng, Kok Pin / Therriault, Joseph / Kang, Min Su / Pascoal, Tharick A / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous8900964. ·1Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China. · grid.452206.7 · 2Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · 0000 0004 0636 696X · grid.276809.2 · 3The McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. · 0000 0004 1936 8649 · grid.14709.3b ·Transl Neurodegener · Pubmed #30311914.

ABSTRACT: Background: Visinin-like protein-1 (VILIP-1) and chitinase-3-like protein 1 (CHI3L1 or YKL-40) in cerebrospinal fluid (CSF) are newly discovered markers indicating neuronal damage and microglial activation, respectively. Phosphorylated tau (p-tau) reflects the neuropathology of Alzheimer's disease (AD) and is useful as diagnostic markers for AD. However, it is unknown whether these biomarkers have similar or complementary information in AD. Methods: We stratified 121 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database into cognitively normal (CN), stable mild cognitive impairment (sMCI), progressive MCI (pMCI), and dementia due to AD. Analysis of covariance (ANOVA) and chi-square analyses, Spearman correlation, and logistic regression models were performed to test the demographic, associations between biomarkers, and diagnostic accuracies, respectively. Linear mixed-effects models were used to evaluate the effects of CSF amyloid-β (Aβ) on above biomarkers within diagnostic groups, the combination of diagnostic group and Aβ status as predictor, and CSF biomarkers as predictors of AD features, including cognition measured by Mini-Mental State Examination (MMSE) and brain structure and white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). Results: P-tau, VILIP-1, and YKL-40 were all predictors of AD diagnosis, but combinations of biomarkers did not improve the diagnostic accuracy (AUC 0.924 for p-tau, VILIP-1, and YKL-40) compared to p-tau (AUC 0.922). P-tau and VILIP-1 were highly correlated ( Conclusions: CSF levels of p-tau, VILIP-1, and YKL-40 may have utility for discriminating between cognitively normal subjects and patients with AD. Increased levels of both VILIP-1 and YKL-40 may be associated with disease degeneration. These CSF biomarkers should be considered for future assessment in the characterization of the natural history of AD.

13 Article The influence of language and culture on cognitive assessment tools in the diagnosis of early cognitive impairment and dementia. 2018

Ng, Kok Pin / Chiew, Hui Jin / Lim, Levinia / Rosa-Neto, Pedro / Kandiah, Nagaendran / Gauthier, Serge. ·a Department of Neurology , National Neuroscience Institute , Singapore , Singapore. · b Alzheimer's Disease Research Unit , The McGill University Research Centre for Studies in Aging , Montreal , Canada. · c Duke-NUS Medical School , Singapore , Singapore. ·Expert Rev Neurother · Pubmed #30286681.

ABSTRACT: INTRODUCTION: Cognitive assessment tools measure cognitive impairment and complement biomarkers to link cognitive symptoms with pathophysiological processes underlying dementia. However, language and cultural differences in multilingual populations can influence the interpretation of cognitive assessment tools when applied in cross-cultural and multinational studies. Areas covered: This article examines the influence of culture and language on the interpretation of the Mini-Mental State Examination, Montreal Cognitive Assessment, and Alzheimer's Disease Assessment Scale-cognitive subscale, which are more commonly used worldwide. It discusses how this impacted multinational studies. Lastly, it presents language-neutral tools such as the Visual Cognitive Assessment Test, which do not require translation when applied in multilingual populations. Expert commentary: Linguistic and cultural variation within tools due to translation and differences in administration introduce method bias and differential item functioning, which influence the interpretation of cognitive scores in multinational studies. The ultimate goal is to have a tool that accurately measures cognitive impairment, yet with minimal influence from linguistic, cultural, educational, and demographic differences, through concerted international efforts to harmonize the development and validation of tools. While recently developed visual-based language-neutral tools show promise in the early detection of cognitive impairment, further validation will be required for these tools to be applied internationally.

14 Article Cerebrospinal fluid synaptosomal-associated protein 25 is a key player in synaptic degeneration in mild cognitive impairment and Alzheimer's disease. 2018

Zhang, Hua / Therriault, Joseph / Kang, Min Su / Ng, Kok Pin / Pascoal, Tharick A / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous3600958. ·Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. · The McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. · Department of Neurology, National Neuroscience Institute, Singapore, Singapore. · The McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. serge.gauthier@mcgill.ca. ·Alzheimers Res Ther · Pubmed #30115118.

ABSTRACT: BACKGROUND: There is accumulating evidence that synaptic loss precedes neuronal loss and correlates best with impaired memory formation in Alzheimer's disease (AD). Cerebrospinal fluid (CSF) synaptosomal-associated protein 25 (SNAP-25) is a newly discovered marker indicating synaptic damage. We here test CSF SNAP-25 and SNAP-25/amyloid-β42 (Aβ42) ratio as a diagnostic marker for predicting cognitive decline and brain structural change in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. METHODS: We stratified 139 participants from the ADNI database into cognitively normal (CN; n = 52), stable mild cognitive impairment (sMCI; n = 22), progressive MCI (pMCI; n = 47), and dementia due to AD (n = 18). Spearman correlation was performed to test the relationships between biomarkers. Overall diagnostic accuracy (area under the curve (AUC)) was obtained from receiver operating curve (ROC) analyses. Cox proportional hazard models tested the effect of CSF SNAP-25 and SNAP-25/Aβ42 measures on the conversion from MCI to AD. Relationships between the CSF SNAP-25 levels, SNAP-25/Aβ42 ratio, and diagnostic groups were tested with linear regressions. Linear mixed-effects models and linear regression models were used to evaluate CSF SNAP-25 and SNAP-25/Aβ42 as predictors of AD features, including cognition measured by the Mini-Mental State Examination (MMSE) and brain structure and white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). RESULTS: CSF SNAP-25 and SNAP-25/Aβ42 were increased in patients with pMCI and AD compared with CN, and in pMCI and AD compared with sMCI. Cognitively normal subjects who progressed to MCI or AD during follow-up had increased SNAP-25/Aβ42 ratio compared with nonprogressors. CSF SNAP-25, especially SNAP-25/Aβ42, offers diagnostic utility for pMCI and AD. CSF SNAP-25 and SNAP-25/Aβ42 significantly predicted conversion from MCI to AD. In addition, elevated SNAP-25/Aβ42 ratio was associated with the rate of hippocampal atrophy in pMCI and the rate of change of cognitive impairment in CN over the follow-up period. CONCLUSIONS: These data suggest that both CSF SNAP-25 and SNAP-25/Aβ42 ratio are already increased at the early clinical stage of AD, and indicate the promise of CSF SNAP-25 and SNAP-25/Aβ42 ratio as diagnostic and prognostic biomarkers for the earliest symptomatic stage of AD.

15 Article In vivo quantification of neurofibrillary tangles with [ 2018

Pascoal, Tharick A / Shin, Monica / Kang, Min Su / Chamoun, Mira / Chartrand, Daniel / Mathotaarachchi, Sulantha / Bennacef, Idriss / Therriault, Joseph / Ng, Kok Pin / Hopewell, Robert / Bouhachi, Reda / Hsiao, Hung-Hsin / Benedet, Andrea L / Soucy, Jean-Paul / Massarweh, Gassan / Gauthier, Serge / Rosa-Neto, Pedro. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, QC, H4H 1R3, Canada. · Montreal Neurological Institute, 3801 University Street, Montreal, QC, H3A 2B4, Canada. · Translational Biomarkers, Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA, 19486, USA. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, QC, H4H 1R3, Canada. pedro.rosa@mcgill.ca. · Montreal Neurological Institute, 3801 University Street, Montreal, QC, H3A 2B4, Canada. pedro.rosa@mcgill.ca. · Douglas Hospital, McGill University, 6875 La Salle Blvd-FBC room 3149, Montreal, QC, H4H 1R3, Canada. pedro.rosa@mcgill.ca. ·Alzheimers Res Ther · Pubmed #30064520.

ABSTRACT: BACKGROUND: Imaging agents capable of quantifying the brain's tau aggregates will allow a more precise staging of Alzheimer's disease (AD). The aim of the present study was to examine the in vitro properties as well as the in vivo kinetics, using gold standard methods, of the novel positron emission tomography (PET) tau imaging agent [ METHODS: In vitro properties of [ RESULTS: In vitro [ CONCLUSIONS: This evaluation shows an [

16 Article Characterizing biomarker features of cognitively normal individuals with ventriculomegaly. 2018

Li, Xiaofeng / Ba, Maowen / Ng, Kok Pin / Mathotaarachchi, Sulantha / Pascoal, Tharick A / Rosa-Neto, Pedro / Gauthier, Serge. ·Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, McGill University, Montreal, Canada. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, Montreal, Canada. · Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China. · Department of Neurology, National Neuroscience Institute, Singapore, Singapore. ·Alzheimers Dement (Amst) · Pubmed #29159265.

ABSTRACT: Introduction: The clinical significance of ventriculomegaly in cognitively normal elderly individuals remains unclear. Methods: We selected cognitively normal individuals (n = 425) from the Alzheimer's Disease Neuroimaging Initiative database and calculated Evans index (EI) based on the ratio of the frontal horn and skull diameter. We defined ventriculomegaly as EI ≥ 0.30, and the participants were stratified into EI ≥ 0.30 group and EI < 0.30 group. Neuropsychological, imaging, and fluid biomarker profiles between the two groups were then compared using regression models. Results: A total of 96 (22.5%) individuals who had ventriculomegaly performed worse on the cognitive tests; showed smaller hippocampal volume but larger caudate, cingulate, and paracentral gyrus volumes; and displayed lower positron emission tomography [ Discussion: Asymptomatic ventriculomegaly might be an early imaging signature of preclinical Alzheimer's disease and/or normal pressure hydrocephalus.

17 Article Author response: Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease. 2017

Gauthier, Serge / Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Chung, Chang-Oh / Benedetti, Andréa L / Shin, Monica / Kang, Min Su / Li, Xiaofeng / Ba, Maowen / Kandiah, Nagaendran / Rosa-Neto, Pedro. ·Montreal. · Singapore. · Verdun, Canada. · Gwangju, Korea. · Chongqing. · Yantai, China. ·Neurology · Pubmed #29084927.

ABSTRACT: -- No abstract --

18 Article The prevalence and biomarkers' characteristic of rapidly progressive Alzheimer's disease from the Alzheimer's Disease Neuroimaging Initiative database. 2017

Ba, Maowen / Li, Xiaofeng / Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous4260924. ·Department of Neurology, Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, People's Republic of China. · Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Douglas Institute, Montreal, Quebec, Canada. · Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China. · Department of Neurology, National Neuroscience Institute, Singapore. ·Alzheimers Dement (N Y) · Pubmed #29067322.

ABSTRACT: INTRODUCTION: The prevalence and detailed biomarkers' characteristic of rapidly progressive Alzheimer's disease (rpAD) remain incompletely understood. METHODS: A total of 312 mild AD patients from the Alzheimer's Disease Neuroimaging Initiative database were chosen and dichotomized into rpAD and non-rpAD groups. We performed the prevalence and comprehensive biomarker evaluation. RESULTS: The prevalence of rpAD was 17.6% in mild AD. Compared with non-rpAD, there were no differences in DISCUSSION: We identified that rpAD commonly existed in mild AD. Cerebral hypometabolism could provide potential clinical differential value for rpAD in the short-term follow-up period.

19 Article Neuropsychiatric symptoms predict hypometabolism in preclinical Alzheimer disease. 2017

Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Chung, Chang-Oh / Benedet, Andréa L / Shin, Monica / Kang, Min Su / Li, Xiaofeng / Ba, Maowen / Kandiah, Nagaendran / Rosa-Neto, Pedro / Gauthier, Serge / Anonymous1420903. ·From the Translational Neuroimaging Laboratory (K.P.N., T.A.P., S.M., C.-O.C., A.L.B., M.S., M.S.K., P.R.-N.) and Alzheimer's Disease Research Unit (K.P.N., X.L., M.B., P.R.-N., S.G.), McGill University Research Centre for Studies in Aging, Montreal, Quebec, Canada · Department of Neurology (K.P.N., N.K.), National Neuroscience Institute, Singapore · Montreal Neurological Institute (P.R.-N.) · Department of Neurology and Neurosurgery (P.R.-N.), McGill University, Montreal, Quebec, Canada · Department of Neurology (X.L.), The Second Affiliated Hospital of Chongqing Medical University, Chongqing · and Department of Neurology (M.B.), Yantai Yuhuangding Hospital Affiliated to Qingdao Medical University, Shandong, PR China. ·Neurology · Pubmed #28404803.

ABSTRACT: OBJECTIVE: To identify regional brain metabolic dysfunctions associated with neuropsychiatric symptoms (NPS) in preclinical Alzheimer disease (AD). METHODS: We stratified 115 cognitively normal individuals into preclinical AD (both amyloid and tau pathologies present), asymptomatic at risk for AD (either amyloid or tau pathology present), or healthy controls (no amyloid or tau pathology present) using [ RESULTS: Individuals with preclinical AD with higher NPI scores had higher [ CONCLUSIONS: The magnitude of NPS in preclinical cases, driven by sleep behavior and irritability domains, is linked to transitory metabolic dysfunctions within limbic networks vulnerable to the AD process and predicts subsequent PCC hypometabolism. These findings support an emerging conceptual framework in which NPS constitute an early clinical manifestation of AD pathophysiology.

20 Article Monoamine oxidase B inhibitor, selegiline, reduces 2017

Ng, Kok Pin / Pascoal, Tharick A / Mathotaarachchi, Sulantha / Therriault, Joseph / Kang, Min Su / Shin, Monica / Guiot, Marie-Christine / Guo, Qi / Harada, Ryuichi / Comley, Robert A / Massarweh, Gassan / Soucy, Jean-Paul / Okamura, Nobuyuki / Gauthier, Serge / Rosa-Neto, Pedro. ·Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. · Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, McGill University, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. · Montreal Neurological Institute/Hospital, Department of Pathology, McGill University Hospital Centre, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. · AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, USA. · Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. · McConnell Brain Imaging Centre, McGill University, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. · Division of Pharmacology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan. · Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. pedro.rosa@mcgill.ca. · Alzheimer's Disease Research Unit, The McGill University Research Centre for Studies in Aging, McGill University, 6825 LaSalle Boulevard, Verdun, Québec, H4H 1R3, Canada. pedro.rosa@mcgill.ca. · Montreal Neurological Institute, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. pedro.rosa@mcgill.ca. · Department of Neurology and Neurosurgery, McGill University, 3801 University Street, Montreal, Québec, H3A 2B4, Canada. pedro.rosa@mcgill.ca. ·Alzheimers Res Ther · Pubmed #28359327.

ABSTRACT: METHODS: Eight participants (five mild cognitive impairment, two Alzheimer's disease, and one progressive supranuclear palsy) had baseline RESULTS: At baseline, CONCLUSIONS: These results indicate that the interpretation of

21 Article Role of cognitive enhancer therapy in Alzheimer's disease with concomitant cerebral white matter disease: findings from a long-term naturalistic study. 2014

Ng, Kok Pin / Ng, Aloysius / Assam, Pryseley / Heng, Esther / Kandiah, Nagaendran. ·Department of Neurology, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore. ·Drugs R D · Pubmed #25063270.

ABSTRACT: BACKGROUND: Evidence is lacking for cognitive enhancer therapy in patients with Alzheimer's disease (AD) and concomitant cerebrovascular disease (mixed AD) as such patients would have been excluded from clinical trials. Earlier studies of mixed AD have focused on large vessel cerebrovascular disease. The influence of small vessel cerebrovascular disease (svCVD) in the form of white matter hyperintensity (WMH) on treatment outcomes in mixed AD has not been addressed. OBJECTIVE: In this long-term naturalistic study, we evaluated the effectiveness of cognitive enhancers in patients with mixed AD with svCVD. METHODS: We conducted a retrospective analysis of a prospective clinical database from a memory clinic of a tertiary hospital. Magnetic resonance imaging WMH was used as a marker of svCVD. Demographic, cognitive, and treatment data were analysed. Linear mixed models with patient-specific random effects were used to evaluate cognitive outcomes over time while adjusting for confounders. RESULTS: Patients with mixed AD (n = 137) or AD without svCVD (pure AD) (n = 28) were studied over a median duration of 28.7 months. Patients with mixed AD had a higher prevalence of hypertension (62.8 vs. 35.7 %, p = 0.011). The majority (75.2 %) of the study sample were managed with monotherapy. Mini Mental State Examination (MMSE) scores decreased over time (-0.04, p = 0.007), and the decrease was similar for both diagnosis groups (-0.03, p = 0.246). Annual estimated mean MMSE decline was 0.84 for pure AD and 0.48 for mixed AD. Similar trends were observed with Montreal Cognitive Assessment (MoCA) scores, with annual estimated mean reduction of 0.72 and 0.48 for pure AD and mixed AD, respectively. CONCLUSION: Cognitive enhancers are effective in slowing the rate of cognitive decline in patients with AD with svCVD. These findings would need to be confirmed in randomized clinical trials.

22 Minor Interaction between APOE-ɛ4 and HMGB1 is associated with widespread cortical thinning in mild cognitive impairment. 2018

Foo, Heidi / Ng, Kok Pin / Tan, Jayne / Lim, Lina / Chander, Russell Jude / Yong, Ting Ting / Kandiah, Nagaendran. ·Department of Neurology, National Neuroscience Institute, Singapore. · Department of Physiology, Centre for Life Sciences, Singapore. · Duke-NUS Medical School, Singapore. ·J Neurol Neurosurg Psychiatry · Pubmed #28659393.

ABSTRACT: -- No abstract --