Connecting late-life depression and cognition with statistical physics based connectomics and sparse Frechet regression
Connecting late-life depression and cognition with statistical physics based connectomics and sparse Frechet regression
批准号:
10190424
负责人:
Alex Leow
金额:
$126.12万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-04-01 至 2024-03-31
关键词:
AgeAgingAllelesAlzheimer&aposs DiseaseAlzheimer&aposs disease riskApolipoprotein EArchivesAreaBRAIN initiativeBrainClinicalCognitionCognitiveComplementDataData SetDementiaDemographic FactorsDepressed moodDiagnosisDiseaseElderlyEquilibriumExhibitsFemaleFunctional disorderGenderGenotypeGraphHippocampus (Brain)HybridsImpaired cognitionIndividualInterventionLate EffectsLearningLinkMathematicsMeasuresMediatingMemoryMental DepressionModelingMoodsNatureNerve DegenerationNeurobiologyNeurocognitiveNeuronsParietal LobePersonsPhysicsPilot ProjectsPreventionProcessRegression AnalysisReportingResourcesRestRisk FactorsRoleSamplingSecondary toStatistical Data InterpretationStructureSynapsesTemporal LobeTestingTimeWomanbasecerebral atrophycognitive developmentcognitive functioncognitive performancecomparison groupconnectomedemographicsferritefollow-upfunctional declinefunctional outcomesgeriatric depressionindexingmalemenmorris water mazemultimodalityneuronal circuitryneuropathologynormal agingnovelpreventprospectiverecruitsecondary analysissextoolvirtualβ-amyloid burden
中文摘要
最近,有几条证据支持突触功能障碍是其中之一
英文摘要
Recently, several lines of evidence have supported that synaptic dysfunction represents one of
the earliest brain changes in Alzheimer’s disease (AD), leading to hyper-excitation in neuronal
circuits. However, network changes related to age, sex and other risk factors such as the
apolipoprotein E (APOE) ε4 allele tend to overlap with disease neuropathology, increasing the
difficulty of separating disease-specific alterations from those related to normal aging
trajectories in males and females (women comprise two thirds of all persons diagnosed with AD
dementia, while female ε4 allele carriers are four times more likely to develop AD than men).
Further compounding the challenges is the potential for psychiatric conditions to influence these
relationships. Specifically, late life depression (LLD) has been proposed as a significant
contributor to accelerated cognitive decline and progression to dementia. While it remains
unclear which neurobiological aspects of LLD represent pathognomonic features, versus co-
occurring aspects of AD, determining their impact on functional outcomes is a significant
opportunity to disentangle the relationship between depression and neurodegenerative
processes in late life.
We will use multi-modal connectomics to analyze excitation-inhibition balance (E-I balance)
in the well-characterized ADNI and ADNI-D samples to elucidate the relationship between late-
life depression and neurodegeneration. Our pipeline will be based on a novel resting-state
structural connectomics (rs-SC) approach that yields a hyperexcitation indicator (HI).
Previously, in a group of cognitively normal APOE-ε4 carriers and age/gender matched non-
carriers we demonstrated a sex-by-age-by-genotype interaction, with significant hyperexcitation
with increasing age only observable in women, but not in men. In particular, results supported
that hyperexcitation in female carriers began to exhibit at age 50 in the default mode network
(DMN). Further, the degree of hyperexcitation was shown to be related to compensatory
recruitment of neuronal resources during a spatial learning memory task (virtual Morris water
maze task). Motivated by this pilot study, we will examine the links between mood (late-life
depression) and subsequent cognitive decline and development of dementia in the context of
synaptic dysfunction.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
CRCNS: Investigating Brain Dynamics through the Lens of Statistical Mechanics
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批准号:10401891
-
项目类别:
-
资助金额:$29.05万
-
财政年份:2020
-
负责人:Alex Leow
-
依托单位:
CRCNS: Investigating Brain Dynamics through the Lens of Statistical Mechanics
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批准号:10222567
-
项目类别:
-
资助金额:$28.87万
-
财政年份:2020
-
负责人:Alex Leow
-
依托单位:
海外基金