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| 1 | Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease显示文摘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 Aβstatus 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(r=0.639,p<0.001)and strongly associated with Aβpathology across clinical stages of AD,while YKL-40 was correlated with Aβpathology in CN and AD groups.VILIP-1 was associated with acceleration of cognitive decline,hippocampal atrophy,and expansion of ventricles in longitudinal analyses.YKL-40 was associated with hippocampal atrophy at baseline and follow-up,while p-tau was only associated with worsening WMH at baseline.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. | Hua Zhang Kok Pin Ng Joseph Therriault Min Su Kang Tharick APascoal Pedro Rosa-Neto Serge Gauthier the Alzheimer’s Disease Neuroimaging Initiative | 2018 | Translational Neurodegeneration2018，7，1： | 5 |
| 2 | Amyloid and tau positive mild cognitive impairment:clinical and biomarker characteristics of dementia progression显示文摘Background:According to the amyloid,tau,neurodegeneration research framework classification,amyloid and tau positive(A+T+)mild cognitive impairment(MCI)individuals are defined as prodromal Alzheimer disease.This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI(pMCI)and those who remained stable MCI(sMCI),and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.Methods:We stratified 197 A+T+MCI individuals into pMCI(n=64)and sMCI(n=133)over 2 years.Demographics and cognitive assessment scores,cerebrospinal fluid(CSF),and neuroimaging biomarkers(18F-florbetapir positron emission tomography mean standardized uptake value ratios[SUVR]and structural magnetic resonance imaging[MRI])were compared between pMCI and sMCI at baseline,12-and 24-month follow-up.Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.Results:pMCI individuals had higher mean 18F-florbetapir SUVR,CSF total-tau(t-tau),and p-tau181P than those in sMCI individuals.pMCI individuals performed poorer in cognitive assessments,both global and domain specific(memory,executive,language,attention,and visuospatial skills)than sMCI.At baseline,there were significant differences in regions of interest of structural MRI between the two groups,including bilateral amygdala,hippocampus and entorhinal,bilateral inferior lateral ventricle,left superior and middle temporal,left posterior and caudal anterior cingulate(P<0.05).Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment,functional assessment questionnaire,and everyday cognition by the patient’s study partner language domain could predict progression to dementia in A+T+MCI within 2 years.Conclusions:In future clinical trials,specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression. | Hong-Chun Wei Bing Li Kok Pin Ng Qing-Xi Fu Sheng-Jie Dong Mao-Wen Ba Min Kong | 2021 | Chinese Medical Journal2021，，14： | 3 |
| 3 | Associations of AT(N) biomarkers with neuropsychiatric symptoms in prechnical Alzheimer’s disease and cognitively unimpaired individuals显示文摘The development of in vivo biomarkers of Alzheimer's disease(AD)has advanced the diagnosis of AD from a clinical syndrome to a biological construct.The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals.While neuropsychiatric symptoms(NPS)are non-cognitive symptoms that are increasingly recognized as early manifestations of AD,the associations of NPS with AD pathophysiology in preclinical AD remain unclear.Here,we review the associations between NPS and AD biomarkers amyloid-(3(Aβ),tau and neurodegeneration in preclinical AD and cognitivelyunimpaired individuals in 19 eligible English-language publications(8 cross-sectional studies,10 longitudinal,1 both cross-sectional and longitudinal).The cross-sectional studies have consistently shown that NPS,particularly depressive and anxiety symptoms,are associated with higher Aβ.The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over time.However,most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology.For the association of NPS and neurodegeneration,two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD,respectively.However,evidence for the association between atrophy and NPS in preclinical AD is less consistent.Therefore,future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N)biomarkers,NPS and cognitive decline,but also to elucidate the contribution of comorbid pathology to preclinical AD. | Kok Pin Ng Hui Chiew Pedro Rosa-Neto Nagaendran Kandiah Zahinoor Ismail Serge Gauthier | 2021 | Translational Neurodegeneration2021，10，1： | 2 |
| 4 | Disturbance decoupled fault reconstruction using cascaded sliding mode observers 显示文摘 | Kok Yew Ng Chee Pin Tan Denny Oetomo | 2012 | Automatica2012，48，5： | 1 |
| 5 | Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer's disease显示文摘Background:Neuropsychiatric symptoms(NPS)are increasingly recognized as early non-cognitive manifestations in the Alzheimer's disease(AD)continuum.However,the role of NPS as an early marker of pathophysiological progression in AD remains unclear.Dominantly inherited AD(DIAD)mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation.Hence,the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies.In this longitudinal study,we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers.Methods:We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer's Network according to their mutation carrier status.The interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire(NPI-Q),age,and estimated years to symptom onset(EYO)as a function of metabolism measured by[^(18)F]flurodeoxyglucose([^(18)F]FDG)positron emission tomography,were evaluated by the mixed-effects regression model with family-level random effects in DIAD mutation carriers and non-carriers.Exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q subcomponents.Then the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression model.Results:A total of 119 mutation carriers and 102 non-carriers were studied.The interaction of higher NPI-Q and shorter EYO was associated with more rapid declines of global and regional[18F]FDG uptake in the posterior cingulate and ventromedial prefrontal cortices,the bilateral parietal lobes and the right insula in DIAD mutation carriers.The neuropsychiatric subsyndromes of agitation,disinhibition,irritability and depression interacted with the EYO to drive the[^(18)F]FDG uptake decline in the DIAD mutation carriers.The interaction of NPI and EYO was not associated with[^(18)F]FDG uptake in DIAD mutation non-carriers.Conclusions:The NPS in cognitively intact DIAD mutation carriers may be a clinical indicator of subsequent metabolic decline in brain networks vulnerable to AD,which supports the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD.Further studies using different methodological approaches to identify NPS in predinical AD are needed to validate our findings. | Kok Pin Ng Tharick A.Pascoal Sulantha Mathotaarachchi Yiong Huak Chan Lai Jiang Joseph Therriault Andrea L.Benedet Monica Shin Nagaendran Kandiah Celia M.T.Greenwood Pedro Rosa-Neto Serge Gauthier Dominantly Inherited Alzheimer Network | 2021 | Translational Neurodegeneration2021，10，1： | 0 |
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