Network level analysis of progressive brain degeneration in autosomal dominant Alzheimer disease
Network level analysis of progressive brain degeneration in autosomal dominant Alzheimer disease
批准号:
10288428
负责人:
Muriah D Wheelock
金额:
$23.14万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2020
资助国家:
美国
项目状态:
已结题
起止时间:
2020-07-01 至 2022-06-30
关键词:
Administrative SupplementAlzheimer&aposs DiseaseAmyloid beta-ProteinAtrophicAwardBiological MarkersBiology of AgingBiometryBrainBrain regionCognitionCognitiveCollaborationsCommunicationComputer softwareDataData AnalysesData SetDementiaDerivation procedureDiseaseFosteringFunctional Magnetic Resonance ImagingFunctional disorderFutureGoalsHumanImpaired cognitionIndividualInheritedLateralLightMeasuresNational Institute on AgingNetwork-basedNeurobehavioral ManifestationsNeuronsOntologyParietalParticipantPathologyPre-Clinical ModelPreventionPrognosisResearchResearch PersonnelResourcesRestScientistSenile PlaquesSerumSignal TransductionSymptomsThinnessValidationage relatedalgorithm developmentanalysis pipelineautosomal dominant Alzheimer&aposs diseaseblood oxygen level dependentblood-based biomarkerbrain behaviorcingulate gyruscohortconnectomedisabilityearly onsetindexinginnovationnetwork architecturenetwork dysfunctionneurofilamentrecruitspatiotemporaltau Proteinstau aggregation
中文摘要
行政补充项目摘要/摘要
英文摘要
ADMINISTRATIVE SUPPLEMENT PROJECT SUMMARY/ABSTRACT
Alzheimer’s disease (AD) is characterized by changes including the accrual of amyloid-b (Ab) plaques and
neurofibrillary tau tangles, cortical thinning, hypometabolism, and disruptions in brain connectivity. However, the
presence of this pathology does not occur simultaneously, but propagates throughout the cortex decades before
symptoms of dementia are apparent. Researchers have noted that Ab, hypometabolism, and tau show consistent
focal disruption beginning in lateral parietal, temporal, and the posterior cingulate gyrus. We hypothesize that
this regional spread of pathology results in disrupted communication among brain networks resulting in
symptoms of cognitive decline. This proposal seeks to 1) characterize the spatiotemporal progression of brain
network degeneration and 2) determine the relationship between neuronal atrophy, brain network dysfunction,
and cognitive decline. Brain networks can be measured using resting state functional magnetic resonance
imaging to index temporal correlations in blood oxygen level dependent signal between brain regions. We will
organize brain regions into canonical functional connectivity brain networks and apply the Network Level Analysis
(NLA) analysis software, developed as part of K99 EB029343, to determine brain network associations with
neuronal atrophy (as indexed with serum neurofilament light; NfL) and symptoms of dementia (as indexed with
a global cognition composite score). NLA is an innovative approach to the analysis of connectome-wide
associations that leverages cross disciplinary biostatistical approaches and an ontological framework, allowing
for derivation of network-based brain-behavior relationships and control of false positive rate at the network level.
This administrative supplement will extend the aims of the original award, which proposed validation of NLA
using Human Connectome Project data, to include applications in AD. Specifically, this administrative
supplement will leverage a fully de-identified pre-existing dataset containing functional connectomes, NfL, and
cognitive measures in participants with autosomal dominant AD (ADAD) recruited from the Dominantly Inherited
Alzheimer Network (DIAN) study. The analysis of data from individuals with ADAD is particularly significant due
to the known timeframe and early onset of cognitive symptoms which allows for modeling of preclinical brain
network degeneration while reducing the contribution of age-related confounds. The proposed analyses of DIAN
data using NLA fulfills the National Institute of Aging Goal A to “Better understand the biology of aging and its
impact on the prevention, progression, and prognosis of disease and disability.” The research team has expertise
in Network Level Analysis (Dr. Wheelock), algorithm development (Dr. Eggebrecht), Alzheimer disease
pathophysiology (Dr. Gordon) and the resources to generate functional connectomes in the DIAN cohort for
secondary data analysis (Dr. Ances). This supplement will foster collaboration between computational scientists
and clinicians and afford opportunities for future collaboration to investigate biomarkers in AD.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.cortex.2021.05.015
发表时间:
2021-09
期刊:
Cortex; a journal devoted to the study of the nervous system and behavior
影响因子:
--
作者:
[Gilbert KE, Wheelock MD, Kandala S, Eggebrecht AT, Luby JL, Barch DM]
通讯作者:
Barch DM
DOI:
10.1016/j.neuroscience.2021.02.014
发表时间:
2021-04-01
期刊:
Neuroscience
影响因子:
3.3
作者:
[Wheelock MD, Goodman AM, Harnett NG, Wood KH, Mrug S, Granger DA, Knight DC]
通讯作者:
Knight DC
Innovative biostatistical approaches to network level analyses of connectome-behavior relationships
-
批准号:10700129
-
项目类别:
-
资助金额:$24.9万
-
财政年份:2022
-
负责人:Muriah D Wheelock
-
依托单位:
Innovative biostatistical approaches to network level analyses of connectome-behavior relationships
-
批准号:10630851
-
项目类别:
-
资助金额:$24.9万
-
财政年份:2022
-
负责人:Muriah D Wheelock
-
依托单位:
Implementing best practices in software design for Network Level Analysis
-
批准号:10839638
-
项目类别:
-
资助金额:$23.33万
-
财政年份:2022
-
负责人:Muriah D Wheelock
-
依托单位:
Innovative biostatistical approaches to network level analyses of connectome-behavior relationships
-
批准号:10206140
-
项目类别:
-
资助金额:$12.63万
-
财政年份:2020
-
负责人:Muriah D Wheelock
-
依托单位:
Innovative biostatistical approaches to network level analyses of connectome-behavior relationships
-
批准号:10055480
-
项目类别:
-
资助金额:$12.63万
-
财政年份:2020
-
负责人:Muriah D Wheelock
-
依托单位: