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Associations of AT(N) biomarkers with neuropsychiatric symptoms in prechnical Alzheimer’s disease and cognitively unimpaired individuals

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Translational Neurodegeneration 2021年第1期10卷 126-139页

作者： Kok Pin Ng Hui Chiew pedro rosa-Neto Nagaendran Kandiah Zahinoor Ismail Serge Gauthier Department of Neurology National Neuroscience InstituteSingaporeSingapore Duke-NUS Medical School SingaporeSingapore Lee Kong Chian School of Medicine-Imperial College London Nanyang Technological UniversitySingaporeSingapore The McGill University Research Centre for Studies in Aging MontrealCanada Hotchkiss Brain Institute and Obrien Institute for Public Health/Departments of Psychiatry Clinical Neurosciencesand Community Health SciencesUniversity of CalgaryCalgaryAlbertaCanada

The development of in vivo biomarkers of Alzheimer's disease(AD)has advanced the diagnosis of AD from a clinical syndrome to a biological *** preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired *** 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 ***,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 ***,most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau *** 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,***,evidence for the association between atrophy and NPS in preclinical AD is less ***,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.

关键词： Neuropsychiatric symptoms Preclinical Alzheimer's disease Mild behavioral impairment Amyloid-β Hyperphosphorylated tau Neurodegeneration

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Prevention strategies for Alzheimer’s disease

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Translational Neurodegeneration 2012年第1期1卷 99-102页

作者： Serge Gauthier Liyong Wu pedro rosa-Neto Jianping Jia McGill Center for studies in Aging McGill UniversityMontrealCanada Neurological Department Xuanwu HospitalCapital UniversityBeijingChina McGill Centre for Studies in Aging(MCSA) McGill University6825Boul.LaSalle BlvdMontrealQC H4H 1R3Canada

Symptomatic treatment during the dementia stage of Alzheimer’s disease(AD)cannot delay or halt the progression of this ***,prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated neurodegenerative condition,and its associated burden for individuals and ***,gender,family history,ApoE4,systolic blood pressure,body mass index,total cholesterol level and physical activity are all used as component of dementia risk *** have been numerous challenges in conducting primary prevention trials in *** strategies for prevention studies include studying those subjects with more risk factors for AD,such as older age,those with a positive family history of late onset AD,and those who are ApoE4 *** of these strategies is designed to increase the probability of developing AD thereby decreasing the sample size or the duration of follow *** strategy would be to target directly the pathophysiology of AD in its preclinical stages and use the biomarkers in prevention trial as surrogate *** will be done first in carriers of dominantly inherited early onset *** this research takes place networks of memory clinics must prepare to transfer new knowledge to persons interested in a preventive approach to AD.

关键词： Alzheimer disease Risk factor Prevention Clinical trial Clinical practice

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In vivo tracking of tau pathology using positron emission tomography (PET) molecular imaging in small animals

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Translational Neurodegeneration 2014年第1期3卷 34-39页

作者： Eduardo Rigon Zimmer Antoine Leuzy Venkat Bhat Serge Gauthier pedro rosa-Neto Translational Neuroimaging Laboratory(TNL) McGill Center for Studies in AgingDouglas Mental Health University InstituteMcGill University6875 La Salle Blv-FBC room 3149MontrealQCH4H 1R3Canada Montreal Neurological Institute(MNI) MontrealCanada Department of Biochemistry Federal University of Rio Grande do Sul(UFRGS)Porto AlegreBrazil Department of Psychiatry McGill UniversityMontrealBrazil

Hyperphosphorylation of the tau protein leading to the formation of neurofibrillary tangles(NFTs)is a common feature in a wide range of neurodegenerative diseases known as tauopathies,which include Alzheimer’s disease(AD)and the frontotemporal dementias(FTDs).Although heavily investigated,the mechanisms underlying the pathogenesis and progression of tauopathies have yet to be fully *** this context,several rodent models have been developed that successfully recapitulate the behavioral and neurochemical features of tau pathology,aiming to achieve a better understanding of the link between tau and *** date,behavioral and biochemical parameters assessed using these models have been conducted using a combination of memory tasks and invasive methods such as cerebrospinal fluid(CSF)sampling or post-mortem ***,several novel positron emission tomography(PET)radiopharmaceuticals targeting tau tangles have been developed,allowing for non-invasive in vivo quantification of tau *** with tau transgenic models and micro-PET,these tracers hold the promise of advancing the development of theoretical models and advancing our understanding of the natural history of AD and non-AD *** this review,we briefly describe some of the most important insights for understanding the biological basis of tau pathology,and shed light on the opportunity for improved modeling of tau pathology using a combination of tau-radiopharmaceuticals and animal models.

关键词： Positron emission tomography Tau molecular agents Tau rodent models Tauopathies

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Cerebrospinal fluid phosphorylated tau,visinin-like protein-1,and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease

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Translational Neurodegeneration 2018年第1期7卷 221-232页

作者： Hua Zhang Kok Pin Ng Joseph Therriault Min Su Kang Tharick APascoal pedro rosa-Neto Serge Gauthier the Alzheimer’s Disease Neuroimaging Initiative Department of Neurology the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Neurology National Neuroscience InstituteSingaporeSingapore The McGill University Research Centre for Studies in Aging McGill UniversityMontrealCanada 不详

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,*** tau(p-tau)reflects the neuropathology of Alzheimer’s disease(AD)and is useful as diagnostic markers for ***,it is unknown whether these biomarkers have similar or complementary information in ***: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 *** 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,*** 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 ***-1 was associated with acceleration of cognitive decline,hippocampal atrophy,and expansion of ventricles in longitudinal ***-40 was associated with hippocampal atrophy at baseline and follow-up,while p-tau was only associated with worsening WMH at ***:CSF levels of p-tau,VILIP-1,and YKL-40 may have uti

关键词： Alzheimer’s disease Amyloid-β Chitinase-3-like protein 1 Phosphorylated tau Visinin-like protein-1

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Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer's disease

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Translational Neurodegeneration 2021年第1期10卷 1-11页

作者： 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 Alzheimer's Disease Research Unit McGill Centre for Studies in AgingMcGill UniversityMontrealQuebecCanada Translational Neuroimaging Laboratory The McGill University Research Centre for Studies in AgingMontrealCanada Departm ent of Neurology National Neuroscience InstituteSingapore CitySingapore Biostatistics Unit Yong Loo Lin School of MedicineNational University of SingaporeSingapore CitySingapore Lady Davis Institute McGill UniversityMontrealCanada Department of Epidemiology Biostatistics and Occupational HealthMcGill UniversityMontrealCanada 不详

Background:Neuropsychiatric symptoms(NPS)are increasingly recognized as early non-cognitive manifestations in the Alzheimer's disease(AD)***,the role of NPS as an early marker of pathophysiological progression in AD remains *** inherited AD(DIAD)mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic ***,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 *** this longitudinal study,we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation ***:We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer's Network according to their mutation carrier *** 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 *** factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q *** the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression ***:A total of 119 mutation carriers and 102 non-carriers were *** 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 *** neuropsychiatric subsyndromes of agitation,disinhibition,irritability

关键词： Neuropsychiatric symptoms Dominantly inherited Alzheimer’s disease Metabolic correlates

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Optimal Portfolio Selection of Wind Power Plants Using a Stochastic Risk-Averse Optimization Model, Considering the Wind Complementarity of the Sites and a Budget Constraint

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Energy and Power Engineering 2020年第8期12卷 459-476页

作者： Luiz A. S. Camargo Laís D. Leonel pedro S. rosa Dorel S. Ramos Department of Power Engineering and Electrical Automation University of S&#227o Paulo (USP) S&#227o Paulo Brazil

This work focuses on the best financial resources allocation to define a wind power plant portfolio, considering a set of feasible sites. To accomplish the problem formulation and solution, the first step was to establish a long-term wind series reconstruction methodology for generating scenarios of wind energy, applying it to study five different locations of the Brazilian territory. Secondly, a risk-averse stochastic optimization model was implemented and used to define the optimal wind power plant selection that maximizes the portfolio financial results, considering an investment budget constraint. In a sequence, a case study was developed to illustrate a practical situation of applying the methodology to the portfolio selection problem, considering five wind power plants options. The case study was supported by the proposed optimization model, using the scenarios of generation created by the reconstruction methodology. The obtained results show the model performance in terms of defining the best financial resources allocation considering the effect of the complementarity between sites, making it feasible to select the optimal set of wind power plants, characterizing a wind plant optimal portfolio that takes into account the budget constraint. The adopted methodology makes it possible to realize that the diversification of the portfolio depends on the investor risk aversion. Although applied to the Brazilian case, this model can be customized to solve a similar problem worldwide.

关键词： Wind Power Plant Portfolio Selection Risk Aversion Stochastic Optimiza-tion

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Effects of Mirror Therapy on the upper Limb Functionality:A study on the perception of Occupational Therapists

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Journal of Geriatric Medicine 2020年第3期2卷 18-21页

作者： António Arsénio Duarte Ana Paula Martins Djanira Gomes João Fragoso Joyce Amado pedro rosa Teachers of the Beja Polytechnic Institute Portugal Graduating Students of the Degree in Occupational Therapy of Beja Polytechnic Institute Portugal

With the visual illusion of the mirror,Mirror Therapy,models the primary somatosensory cortex,cortical and muscular excitability,stimulating cortical reorganization and sensorimotor *** have shown to be effective in improving motor function in short and medium term,in activities of daily living,in visuospatial neglect and in reducing pain,especially in patients with complex regional pain ***:To report the perception of Occupational Therapists regarding the application of Mirror Therapy in professional ***,what factors lead to its application,what are the effects and benefits of the technique,what are its advantages and ***:In the perception of Occupational Therapists,the Mirror Therapy technique has the following benefits:significant decrease in pain,improved sensitivity and functionality of the upper limb,unblocking movements in the affected limb,decreased phantom pain;as negative aspects:difficulties in spatial/environmental control,patient's perceptual/cognitive skills,high level of concentration/attention,absence of scientific evidence in neurological ***:For the interviewed Occupational Therapists,the Mirror Therapy is a safe and useful technique to be applied in your professional practice that has been showing positive results in the functional recovery of patients,however,it lacks studies that identify the appropriate time to start its application and the explanation of an intervention protocol.

关键词： Occupational therapy Mirror therapy Upper limb functionality Rehabilitation

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Regulation of Pollen Foraging Activity in Apis mellifera Africanized Honeybees Colonies

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Agricultural Sciences 2016年第6期7卷 335-340页

作者： Erica Gomes de Lima Simone Cristina Camargo pedro da rosa Santos Jose Washington Santos Oliveira Vagner de Alencar Arnaut de Toledo Universidade Estadual de Maringa Maringa Brazil Universidade Federal de Sergipe Sergipe Brazil Departamento de Zootecnia Universidade Estadual de Maringa Maringa Brazil

Efficient honey production requires knowledge about the behavior of the workers and the parameters that influence the strength of the colony. In this study, the objective was to analyze the interaction between the foraging behavior of worker honeybees and pollen storage levels in Africanized honeybees colonies. Colonies with low pollen storage increased pollen intake rates, but this value was 15% lower than colonies with high pollen storage, demonstrating a direct relationship between the pollen storage levels and foraging activity. The difference in pollen intake rates varied according to the number of foraging honeybees and pollen load collected by each individual. Under both high and low pollen storage, colonies returned pollen storage to initial level within 16 days, suggesting that honeybees regulate pollen storage levels around a homeostatic set point. Relationship between pollen storage levels and colony brood production was also found, indicating how alterations in the behavior of each individual can affect the strength of the colony.

关键词： Comb Mapping Honeybee Nutrition Management in Beekeeping Behavior

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Numerical and Experimental Simulation of the Invert Forming of Thin-Walled Tubes Using a Die

Numerical and Experimental Simulation of the Invert Forming ...

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The Sixth World Congress on Computational Mechanics in Conjunction with the Second Asian-Pacific Congress on Computational Mechanics

作者： pedro A.rosa C.S.Li Jorge M.C.Rodrigues Paulo A.F.Martins Department of Mechanical Engineering Instituto Superior Técnico Av. Rovisco Pais 1049-001 Lisbon Portugal Portugal The State Key Lab of Rolling and Automation Northeastern University Shenyang 110004 China

This paper presents a comprehensive theoretical and experimental investigation of the inversion of thin-walled tubes using a die with the purpose of examining the plastic deformation mechanics, and analysing the influence of design parameters, material strain-hardening and interface friction on the overall formability of the process. Theoredcal investigation is supported by numerical predictions based on the finite element flow formulation and the overall methodology is assessed by means of experimental tests on industrial A16060 Aluminium alloy tubes under laboratory-controlled conditions.

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Perspectives on a collaborative Canada-China research program on diagnostic biomarkers for pre-dementia stages of Alzheimer’s disease

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Journal of Translational Neuroscience 2017年第3期2卷 1-6页

作者： Serge Gauthier Jianping Jia Sylvie Belleville Simon Cloutier Dessa Sadovnick Colleen Guimond Laura Robb Mario Masellis Guy A Rouleau Liyong Wu pedro rosa-Neto McGill Center for Studies in Aging Douglas Mental Health Research Institute Montreal H4H IR3 Canada Innovation Center for Neurological Disorders Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China Beijing Key Laboratory of Geriatric Cognitive Disorders Beijing 100053 China Clinical Center for Neurodegenerative Disease and Memory Impairment Capital Medical University Beijing 100053 China Center of Alzheimer's Disease Beijing Institute for Brain Disorders Beijing 100053 China Key Laboratory of Neurodegenerative Diseases Ministry of Education Beijing 100053 China National Clinical Research Center for Geriatric Disorders Beijing 100053 China Institut Universitaire de Gériatrie de Montréal Montréal H3W IW5 Canada Department of Medical Genetics University of British Columbia Vancouver V6T IZ4 Canada Division of Neurology Department of Medical Genetics University of British Columbia Vancouver V6T IZ4 Canada Division of Neurology/Department of Medicine Sunnybrook Health Sciences Centre University of Toronto Toronto M5S 3H7 Canada Hurvitz Brain Sciences Research Program Sunnybrook Research Institute Toronto M4N 3M5 Canada Montreal Neurological Institute Montréal H3A 2B4 Canada Department of Neurology Xuanwu Hospital Capital Medical University Beijing 100053 China

As biomarkers are important in the early diagnosis ofAlzheimer’s disease （AD）, the frst collab-orative work of recruiting early-onset familial AD （EO-FAD） families in Canada and China was initiated in 2012. The registration networks have collected hundreds of pedigrees, for which genetic screening, neuropsycholog-ical tests and amyloid and tau imaging was used to study diagnostic biomarkers for preclinical and mild cognitive impairment （MCI） stages of AD. Besides identifying ped-igrees with novel mutations in presenilins （PSENs）/amy-loid precursor protein （APP）, the program has benefted training of Chinese research fellows, AD clinical trials forprevention,the ethical concernsfor clinical fndings, and other collaborative projects with Chinese investiga-tors. Further research of the collaborative program may facilitate the testing and clinical use of novel treatments for EOFAD and late onset AD and contribute to dementia prevention strategies in Canada and China.

关键词： registration network early-onset fa-milial Alzheimer’s disease (EOFAD) mutation neuro-psychological testing

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