Cognitive impairment in the DPPOS cohort and its neuropathologic, neurophysiologic, sociodemographic, and behavioral correlates
Cognitive impairment in the DPPOS cohort and its neuropathologic, neurophysiologic, sociodemographic, and behavioral correlates
批准号:
10507634
负责人:
James McCallum Noble
金额:
$41.37万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-09-01 至 2027-08-31
关键词:
Alzheimer&aposs DiseaseAlzheimer&aposs disease related dementiaAmyloidAmyloid beta-42AttenuatedBehavioralBiological MarkersBrain imagingCategoriesCerebrovascular DisordersCharacteristicsClassificationCognitionCognition DisordersCohort StudiesDementiaEducationEthnic OriginEthnic groupFemaleGlial Fibrillary Acidic ProteinGoalsIRS1 geneImpaired cognitionIncidenceInfarctionInsulinInsulin ReceptorInsulin ResistanceKnowledgeLightMeasuresMetabolicNational Institute on AgingNerve DegenerationNeuronsNon-Insulin-Dependent Diabetes MellitusNot Hispanic or LatinoObstructive Sleep ApneaOutcome StudyParticipantPathologicPathologyPeripheralPersonsPharmaceutical PreparationsPlasmaPopulationPositron-Emission TomographyPrediabetes syndromePrevalencePreventionProto-Oncogene Proteins c-aktRaceResearchRestRiskSamplingSleep disturbancesThickTyrosineUnited StatesVascular DementiaWhite Matter Hyperintensityadjudicationagedcognitive testingdepressive symptomsdiabetes prevention programepidemiology studyextracellular vesicleshigh riskhigh risk populationimaging biomarkerinsulin signalingliteracymild cognitive impairmentneurofilamentneuroimagingneuroinflammationneuropathologyneurophysiologypoor sleepsexsleep qualitysociodemographic factorssociodemographicstau Proteinsvascular cognitive impairment and dementiawhite matter
中文摘要
本项目的目标是描述认知功能衰退、轻度认知功能衰退的存在及其相关性。
糖尿病预防项目结果研究(DPPOS)队列中的损害[MCI]和痴呆。
许多流行病学研究表明,糖尿病前期(PRED)和2型糖尿病(T2D)是相关的
有较高的认知障碍风险。然而,关于PRED患者认知障碍的知识差距仍然存在
和T2D:(A)除了血管因素对认知障碍和痴呆症的影响外,还有哪些神经病理因素
(VCID)?(B)神经性胰岛素调节失调是否存在,是否与外周胰岛素抵抗有关?
PRED和T2D的特点?(C)这些联系是否因相关的社会人口统计数据,包括性别而有所不同,
种族/民族、教育程度和识字率?(D)是否与行为相关者有关
(睡眠障碍和抑郁症状),在PRED和T2D中也很常见?我们将描述遗忘者的特征
以及所有参与者的非遗忘性认知功能下降、MCI和痴呆(n=1979)。我们将测量血浆
淀粉样蛋白(Aβ42/40比率)、tau(ptau-181)、神经变性(神经丝光)的生物标记物,以及
所有参与者的神经炎症(胶质纤维酸性蛋白[GFAP]),以及淀粉样脑成像标记物,
神经变性(皮质厚度)、脑血管疾病(白质高信号[WMH]和
在650名参与者的子样本中,研究了脑梗塞)、脑白质微结构和功能连通性。我们会
用血浆ptau-181和淀粉样正电子研究AD的连续性和非AD的病理改变
发射断层扫描(PET),遵循国家老龄研究所(NIA)/阿尔茨海默氏症协会(AA)
研究框架,并将探索tau、神经退行性变、神经炎症和VCID的特征。
我们将在ALL中分离全循环细胞外小泡(EVS)和神经元来源丰富的EVS(NEVS)
参与者一次检查全身和神经元胰岛素信号。我们将通过
具体目标如下:(1)检查遗忘性和非遗忘性认知的患病率和发生率
衰退、MCI和痴呆,并检查它们与淀粉样蛋白、tau、神经退行性变、
神经炎症和VCID;(2)检查认知综合征与系统性和慢性阻塞性肺疾病的关系
使用NEVS测量神经元胰岛素信号。(3)考察社会人口学因素的关联性
包括性别、种族/民族、教育和识字,有认知能力下降、MCI和痴呆症,以及
神经病理生物标志物;(4)探讨抑郁症状、睡眠质量和
阻塞性睡眠呼吸暂停伴认知功能减退、MCI和痴呆症。我们还将探讨它们与
神经病理学的生物标志物。我们还将探讨(A)神经元胰岛素信号是否与外周血细胞有关
与项目2合作的代谢测量;(B)AIMS 1和2中的结果是否因使用T2D而不同
与项目3合作的药物;(C)与认知综合征合作的生理相关性
项目4.
英文摘要
The goal of this project is to characterize the presence and correlates of cognitive decline, mild cognitive
impairment [MCI] and dementia in the Diabetes Prevention Program Outcomes Study (DPPOS) cohort.
Numerous epidemiologic studies have shown that pre-diabetes (PreD) and type 2 diabetes (T2D) are associated
with higher risk of cognitive impairment. However, gaps in knowledge remain about cognitive impairment in preD
and T2D: (a) What is the neuropathology other than vascular contributions to cognitive impairment and dementia
(VCID)? (b) Is neuronal insulin dysregulation present, and is it related to peripheral insulin resistance
characteristic of preD and T2D? (c) Do the associations differ by pertinent sociodemographics, including sex,
race/ethnicity, educational attainment, and literacy? (d) Are the associations related to behavioral correlates
(sleep disturbances and depressive symptoms), also common in preD and T2D? We will characterize amnestic
and non-amnestic cognitive decline, MCI, and dementia, in all participants (n =1979). We will measure plasma
biomarkers of amyloid (Aβ42/40 ratio), tau (ptau-181), neurodegeneration (neurofilament light [NfL]), and
neuroinflammation (glial fibrillary acidic protein [GFAP]) in all participants, and brain imaging markers of amyloid,
neurodegeneration (cortical thickness), cerebrovascular disease (white matter hyperintensities [WMH] and
infarcts), white matter microstructure, and functional connectivity, in a subsample of 650 participants. We will
characterize the AD continuum and non-AD pathologic change using plasma ptau-181 and Amyloid Positron
Emission Tomography (PET), following the National Institute on Aging (NIA)/Alzheimer’s Association (AA)
research framework, and will explore characterization by tau, neurodegeneration, neuroinflammation, and VCID.
We will isolate total circulating extracellular vesicles (EVs) and neuronal origin-enriched EVs (nEVs) in all
participants once to examine systemic and neuronal insulin signaling. We will achieve our goal through the
following specific aims: (1) To examine the prevalence and incidence of amnestic and non-amnestic cognitive
decline, MCI and dementia, and examine their association with biomarkers of amyloid, tau, neurodegeneration,
neuroinflammation, and with VCID; (2) To examine the association of cognitive syndromes with systemic and
neuronal insulin signaling measured using nEVs. (3) To examine the association of sociodemographic factors
including sex, race/ethnicity, education, and literacy, with cognitive decline, MCI, and dementia, and
neuropathology biomarkers; (4) To explore the association of depressive symptoms, sleep quality, and
obstructive sleep apnea with cognitive decline, MCI, and dementia. We will also explore their association with
biomarkers of neuropathology. We will also explore (a) whether neuronal insulin signaling is related to peripheral
metabolic measures collaborating with Project 2; (b) whether findings in aims 1 and 2 vary by use of T2D
medications collaborating with Project 3; (c) the physical correlates of cognitive syndromes collaborating with
Project 4.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
A Longitudinal Study of Periodontal Infections and Alzheimer's Disease: The WHICAP Ancillary Study of Oral Health
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批准号:10381292
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项目类别:
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资助金额:$80.98万
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财政年份:2021
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负责人:James McCallum Noble
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依托单位:
A Longitudinal Study of Periodontal Infections and Alzheimer's Disease: The WHICAP Ancillary Study of Oral Health
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批准号:10631203
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项目类别:
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资助金额:$79.23万
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财政年份:2021
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负责人:James McCallum Noble
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依托单位:
Clinical Core
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批准号:10668237
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项目类别:
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资助金额:$85.79万
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财政年份:2020
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负责人:James McCallum Noble
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依托单位:
Clinical Core
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批准号:10413094
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项目类别:
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资助金额:$87.37万
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财政年份:2020
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负责人:James McCallum Noble
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依托单位:
Clinical Core
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批准号:10187486
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项目类别:
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资助金额:$84.43万
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财政年份:2020
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负责人:James McCallum Noble
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依托单位:
Old SCHOOL Hip Hop: A randomized controlled trial to improve dementia knowledge
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批准号:9218495
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项目类别:
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资助金额:$80.74万
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财政年份:2017
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负责人:James McCallum Noble
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依托单位:
Periodontitis Exposure and Risk of Incident Dementia
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批准号:8732842
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项目类别:
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资助金额:$80.0万
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财政年份:2013
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负责人:James McCallum Noble
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依托单位:
Periodontitis Exposure and Risk of Incident Dementia
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批准号:8735125
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项目类别:
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资助金额:$78.71万
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财政年份:2013
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负责人:James McCallum Noble
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依托单位:
Clinical Core
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批准号:9919931
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项目类别:
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资助金额:$88.78万
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财政年份:--
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负责人:James McCallum Noble
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依托单位:
国内基金
海外基金
新型F-18标记香豆素衍生物PET探针的研制及靶向Alzheimer's Disease 斑块显像研究
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依托单位:
阿尔茨海默病(Alzheimer's disease,AD)动物模型构建的分子机理研究
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批准号:31060293
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批准年份:2010
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依托单位:
跨膜转运蛋白21(TMP21)对引起阿尔茨海默病(Alzheimer'S Disease)的γ分泌酶的作用研究
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批准年份:2009
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负责人:董贵成
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依托单位: