Exercise for Brain Health with Increased Genetic Risk for Alzheimer's Disease
Exercise for Brain Health with Increased Genetic Risk for Alzheimer's Disease
批准号:
10407361
负责人:
JEROME CARSON SMITH
金额:
$60.8万
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:
2021-06-01 至 2023-04-30
关键词:
AddressAdministrative SupplementAerobic ExerciseAllelesAlzheimer associated neurodegenerationAlzheimer disease preventionAlzheimer&aposs DiseaseAlzheimer&aposs disease riskAmyloidApolipoprotein EAttenuatedAuditoryBiological MarkersBrainBrain regionCOVID-19 pandemicCardiovascular systemCerebrovascular CirculationClinicalCognitionCognitiveCommunitiesDementiaDiscriminationDiseaseDisease ProgressionElderlyEpisodic memoryExerciseGenetic RiskHealthImpaired cognitionInterventionKnowledgeMagnetic Resonance ImagingMeasuresMemoryMetabolicNamesNeuronsOutcomePerformancePhysical FunctionPhysical activityPrimary PreventionPublic HealthPublishingQuality of lifeRandomizedRestRetirementRiskRunningSupervisionSymptomsTestingThickVerbal Learningapolipoprotein E-4basebrain healthcognitive functioncomorbiditycostexercise interventionexercise trainingflexibilityimprovedimproved functioninginnovationintervention effectmagnetic resonance imaging biomarkermemory retrievalmodifiable lifestyle factorsneural networknovelparent projectpost interventionprospectiveresponseside effect
中文摘要
项目总结。载脂蛋白E-e4 (APOE-e4)等位基因携带者在很大程度上是存在的
英文摘要
PROJECT SUMMARY. Apolipoprotein E epsilon4 (APOE-e4) allele carriers are known to be at substantially
greater risk for cognitive decline and Alzheimer’s disease (AD). Yet, APOE-ε4 allele inheritance is an imperfect
predictor of who will develop clinical symptoms of the disease, suggesting that modifiable lifestyle factors such
as exercise may moderate its influence on disease progression. Our team is uniquely qualified, and we have
published several preliminary studies showing that physical activity may offer protection for APOE-ε4 allele
carriers from AD-related neurodegeneration and cognitive decline. Interventions, such as exercise, that even
modestly delay the onset of cognitive impairment or improve cognitive function in healthy APOE-e4 carriers will
have a major public health impact. It is not yet known, however, if exercise prospectively modifies the disease
trajectory in healthy asymptomatic older adults who are at increased genetic risk for AD. The focus and
innovative aspect of our proposal is to test the hypothesis that exercise training will improve the efficiency of neural
networks during memory retrieval, increase resting cerebral blood flow, neural network connectivity, and cortical
thickness, and improve episodic memory performance in APOE-e4 allele carriers. There are three key knowledge
gaps regarding exercise as a primary prevention of cognitive decline in those at genetic risk for AD. First, it has not
yet been firmly established that exercise improves the function and efficiency of neuronal networks during cognition,
including memory retrieval, in APOE-e4 allele carriers. Second, it is unknown if the neurotrophic and increased
resting cerebral blood flow effects of exercise extend to APOE-e4 allele carriers. Third, it has not been demonstrated
that an exercise intervention will have lasting effects that delay cognitive decline or conversion to MCI. The novel and
distinguishing feature of our proposal is to address the first two knowledge gaps with MRI and cognitive outcomes
after exercise training in cognitively intact older APOE-e4 allele carriers. Cognitively intact APOE-e4 allele carriers
will be randomly assigned to 6-months of either supervised moderate intensity aerobic exercise training (ET) or
supervised flexibility exercise control (FC). The ET and FC each contain a group-based exercise component
and are run in retirement communities. Our primary aims are to compare pre-intervention to post-intervention
changes in 1) MRI biomarkers; and 2) episodic memory performance measured by the Rey Auditory Verbal
Learning Test (RAVLT). We hypothesize that after ET compared to FC, brain activation during memory
retrieval will be reduced, resting cerebral blood flow and functional connectivity will increase in frontal regions,
and episodic memory performance will improve. Outcomes in response to the intervention will be measured at
baseline and 6 months. Our famous name discrimination task has several advantages to track the effects of
any intervention on neural network efficiency and activates brain regions associated with the “default mode
network”, which is known to harbor amyloid and to be disrupted with progression to AD. This administrative
supplement related to COVID-19 pandemic delays and costs does not extend the scope of the parent project.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
Neural Mechanisms for Associations Between Fitness and Cognition in Aging
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批准号:10913650
-
项目类别:
-
资助金额:$64.25万
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财政年份:2023
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负责人:JEROME CARSON SMITH
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依托单位:
Physiological Responses to Pictures and Exercise in Dysphoria
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批准号:6646949
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项目类别:
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资助金额:$4.8万
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财政年份:2003
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负责人:JEROME CARSON SMITH
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依托单位:
Physiological Responses to Pictures and Exercise in Dysphoria
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批准号:6799644
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项目类别:
-
资助金额:$4.89万
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财政年份:2003
-
负责人:JEROME CARSON SMITH
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依托单位:
海外基金