Aging and Exercise Effects of Dural Lymphatic Clearance in Healthy Human and Diabetic Brains
健康人和糖尿病大脑中硬脑膜淋巴清除的衰老和运动影响
基本信息
- 批准号:10420651
- 负责人:
- 金额:$ 224.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-05-01 至 2025-04-30
- 项目状态:未结题
- 来源:
- 关键词:AdultAffectAgeAgingAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAmericanAmyloid beta-ProteinAnatomyAnimalsArachnoid materBlood VesselsBrainCerebrospinal FluidContrast MediaCytoplasmic GranulesDataDiabetes MellitusDiffuse Cerebral Sclerosis of SchilderDiseaseDura MaterExerciseExtracellular SpaceGadoliniumGoalsHealth StatusHippocampus (Brain)HumanImpaired cognitionInjectionsIntercellular FluidIntrathecal InjectionsIonizing radiationLinkLiquid substanceLymphLymphaticLymphatic clearanceMagnetic Resonance ImagingMeasurementMeasuresMeningesMethodologyMethodsMovementMusNeuraxisNeurodegenerative DisordersNon-Insulin-Dependent Diabetes MellitusPathway interactionsPatientsPerfusionPhasePhysical ExercisePhysical activityPlayPrevalenceRattusReportingResearchRisk FactorsRodentRoleRunningSiteSleepSuperior sagittal sinusSystemTechniquesTestingTimeTracerVascular Diseasesage effectage groupagedaging brainbasecognitive functioncohortdiabeticglymphatic clearanceglymphatic dysfunctionglymphatic systemhealthy aginghuman old age (65+)human subjectimprovedin vivointerstitiallymphatic vesselmouse modelnonhuman primatenormal agingnovelpre-clinicalpreventprotein metabolitepublic health relevancesextemporal measurementwasting
项目摘要
One in 10 Americans age 65 and older (10%) has Alzheimer’s disease (AD). Among type-2 diabetes mellitus
(DM) patients, nearly 70% develop AD with aging. Numerous studies support the association between DM and
AD. AD is a slowly progressive, irreversible neurodegenerative disease with a long preclinical phase lasting up
to 20 years; the prevalence of AD in DM increases in later years. DM is a known risk factor for vascular disease
and is associated with diffuse sclerosis in microvasculature. The relationship between these two diseases and
the mechanisms that link them together are not fully understood, but slower glymphatic clearance in DM patients
is expected to play a significant role. The concept of glymphatics in the brain was pioneered by Negergaard, who
identified a system by which soluble proteins and metabolites are eliminated from the central nervous system
via cerebrospinal fluid (CSF) and interstitial fluid (ISF) exchange in the paravascular space. Studies supporting
its importance continue to be expanded upon and validated in ongoing research, primarily in rodents. Sleep and
physical activity have been reported to accelerate glymphatic clearance. During sleep, a nearly 60% increase in
clearance of rat brain wastes has been observed, caused by expansion and contraction of the extracellular space.
Additional studies have shown that glymphatic clearance decreases with increasing age but can be increased
transiently in aged mice by voluntary wheel running exercises. More recently, in humans, use of a gadolinium-
based contrast agent (GBCA) via intrathecal injection allows for observation of glymphatic clearance as a tracer,
albeit over a long period. However, this method is limited by its invasiveness, and by the unknown effect of the
GBCA tracer on the in vivo time-course of glymphatic clearance. Physical exercise has been reported to improve
clearance of brain Aβ in rats. Recent small animal studies show GBCA clearance in the interstitial space slowed
by a factor of three in the hippocampus of DM rats. DM rats also showed decline in cognitive function compared
to non-DM rats. Although these studies suggest that reduced glymphatic clearance is important for cognitive
decline in DM rats, interpretation is limited by possible underlying changes between DM and non-DM rats, and
effects of GBCA on CSF clearance. Using a novel, non-invasive, non-contrast MRI techniques we propose to
study dural lymphatic clearance in DM and non-DM human brains, physical activity-induced clearance in
parasagittal dura (PSD) and arachnoid granulations (AGs) fluid at meninges in humans. Our challenges include
identification of PSD and AGs and measurement of subtle changes in dural lymphatic fluid clearance at meninges.
To overcome these challenges, we will develop MR techniques to clarify i) the anatomy of PSD, AG, and superior
sagittal sinus, ii) identify the detailed clearance pathway of dural lymphatic fluid; iii) obtain dural lymphatic fluid
perfusion measures; iv) evaluate the age and exercise effects in healthy subjects; and v) compare the dural
lymphatic perfusion of DM patients with age-, sex-matched healthy adults. We expect that dural lymphatic
perfusion measures will be different and altered with exercise, as compared to healthy aging subjects.
十分之一的65岁及以上的美国人(10%)患有阿尔茨海默病(AD)。2型糖尿病患者
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Age-related Decline of Intrinsic Cerebrospinal Fluid Outflow in Healthy Humans Detected with Non-contrast Spin-labeling MR Imaging.
使用非对比自旋标记 MR 成像检测健康人体内固有脑脊液流出量与年龄相关的下降。
- DOI:10.2463/mrms.mp.2022-0117
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Malis,Vadim;Bae,WonC;Yamamoto,Asako;McEvoy,LindaK;McDonald,MarinA;Miyazaki,Mitsue
- 通讯作者:Miyazaki,Mitsue
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Mitsue Miyazaki其他文献
Mitsue Miyazaki的其他文献
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{{ truncateString('Mitsue Miyazaki', 18)}}的其他基金
MR evaluation of macro- and micro-vascularity in diabetic peripheral artery disease
糖尿病外周动脉疾病大血管和微血管的 MR 评估
- 批准号:
10037537 - 财政年份:2020
- 资助金额:
$ 224.75万 - 项目类别:
MR evaluation of macro- and micro-vascularity in diabetic peripheral artery disease
糖尿病外周动脉疾病大血管和微血管的 MR 评估
- 批准号:
10397433 - 财政年份:2020
- 资助金额:
$ 224.75万 - 项目类别:
MR evaluation of macro- and micro-vascularity in diabetic peripheral artery disease
糖尿病外周动脉疾病大血管和微血管的 MR 评估
- 批准号:
10611908 - 财政年份:2020
- 资助金额:
$ 224.75万 - 项目类别:
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