Longitudinal Investigation of Cardiorespiratory Fitness and AD Biomarkers in an At-Risk Cohort

高危人群心肺健康和 AD 生物标志物的纵向调查

• 批准号: 10535455
• 负责人: OZIOMA C OKONKWO
• 金额: $ 92.9万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-15 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10535455
• 关键词: Abate; Accelerometer; Address; Adult; Aerobic Exercise; Aging; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease risk; Alzheimer' s disease therapy; Alzheimer’s disease biomarker; Amyloid beta-Protein; Attention; Attenuated; Biological Markers; Blood Vessels; Cerebrovascular Circulation; Clinical; Clinical Trials; Cognition; Cognitive; Cohort Studies; Compensation; Data; Dementia; Dependence; Disease; Elderly; Enrollment; Epidemic; Etiology; Evaluation; Exclusion; Exercise Test; Failure; Family; Functional disorder; Future; Genetic Risk; Goals; Hippocampus; Human; Individual; Investigation; Knowledge; Link; Magnetic Resonance Imaging; Measures; Mediating; Nerve Degeneration; Participant; Pathogenicity; Patient Self-Report; Peripheral; Persons; Pharmacotherapy; Phenotype; Physical activity; Physiological; Play; Positioning Attribute; Positron-Emission Tomography; Public Health; Recording of previous events; Registries; Research; Resources; Risk; Risk Reduction Behavior; Role; Seminal; Spinal Puncture; Symptoms; Target Populations; Testing; Therapeutic; Transducers; Wisconsin; Work; abeta deposition; active lifestyle; age related; animal data; arterial stiffness; baby boomer; brain volume; cardiorespiratory fitness; cohort; effective therapy; epidemiology study; glucose metabolism; hippocampal atrophy; insight; insulin sensitivity; longitudinal design; middle age; mild cognitive impairment; multimodality; neuroprotection; novel; prevent; prospective; resilience; sex; tau Proteins; tau-1; β-amyloid burden

PROJECT SUMMARY/ABSTRACT Currently-available drug treatments for Alzheimer's disease (AD) are not curative. Furthermore, findings from clinical trials testing novel disease-modifying therapeutics have been disappointing. Accordingly, the urgency of alternative approaches for halting the global crisis posed by AD cannot be overstated. Although data from cohort and epidemiological studies have long suggested a strong link between physical activity and dementia due to AD, the question of whether physical activity modulates the underlying pathophysiology of AD has only recently begun receiving attention. While the emerging evidence appears overall supportive of such a role for physical activity, several critical knowledge gaps persist. First, past studies have been largely cross-sectional. This leaves unresolved the possibility that observed effects simply reflect reverse causation. Second, “physical activity” has been assessed via a variety of approaches including self-report, activity trackers, and maximal graded exercise testing, leading to conflicting findings. Third, because past research has primarily been done in elderly persons, little is known about the potential influence of physical activity on AD risk in midlife, when most AD-related changes begin. Lastly, there is need for a better understanding of the mechanisms by which physical activity exerts its salutary effects. To address these gaps in knowledge (1) we focus this project on cardiorespiratory fitness (CRF), which constitutes the physiological nexus for *habitual* physical activity, (2) we employ a longitudinal design, which would allow us rigorously exclude the possibility of reverse causation, (3) we study a cohort of late-middle-aged adults who are, in principle, potentially only at the inceptive stages of AD, and (4) we investigate vascular and glucoregulatory function as viable transducers of the link between CRF and AD pathophysiology. Importantly, because the participants targeted for this study are being followed longitudinally through the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center, we will be uniquely positioned in the long term to elucidate the impact of midlife CRF on clinical endpoints of mild cognitive impairment and dementia. In sum, the multimodal and integrative study proposed here stands to provide critical insights into CRF as a potentially viable therapeutic for altering disease trajectory in the early stages of AD, prior to pervasive neurodegeneration, thereby delaying the emergence of clinical symptoms.

项目总结/文摘

项目成果

Cross-sectional associations of CSF tau levels with Rey's AVLT: A recency ratio study.

• DOI: 10.1037/neu0000821
• 发表时间: 2023-09
• 期刊: NEUROPSYCHOLOGY
• 影响因子: 2.4
• 作者: Bruno, Davide;Zinkunegi, Ainara Jauregi;Pomara, Nunzio;Zetterberg, Henrik;Blennow, Kaj;Koscik, Rebecca Langhough;Carlsson, Cynthia;Bendlin, Barbara;Okonkwo, Ozioma;Hermann, Bruce P.;Johnson, Sterling C.;Mueller, Kimberly D.
• 通讯作者: Mueller, Kimberly D.

Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study.

• DOI: 10.1177/0271678x211021313
• 发表时间: 2021-11
• 期刊: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
• 作者: Wang R;Oh JM;Motovylyak A;Ma Y;Sager MA;Rowley HA;Johnson KM;Gallagher CL;Carlsson CM;Bendlin BB;Johnson SC;Asthana S;Eisenmenger L;Okonkwo OC
• 通讯作者: Okonkwo OC

Truly Cross-fit: The Association of Exercise and Clinical Outcomes: Introduction to a JINS Special Section.

• DOI: 10.1017/s1355617721001119
• 发表时间: 2021-09
• 期刊: JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
• 影响因子: 2.6
• 作者: Smith, Glenn E.;Okonkwo, Ozioma C.
• 通讯作者: Okonkwo, Ozioma C.

An examination of a novel multipanel of CSF biomarkers in the Alzheimer's disease clinical and pathological continuum.

• DOI: 10.1002/alz.12204
• 发表时间: 2021-03
• 期刊: Alzheimer's & dementia : the journal of the Alzheimer's Association
• 作者: Van Hulle C;Jonaitis EM;Betthauser TJ;Batrla R;Wild N;Kollmorgen G;Andreasson U;Okonkwo O;Bendlin BB;Asthana S;Carlsson CM;Johnson SC;Zetterberg H;Blennow K
• 通讯作者: Blennow K

Insulin Homeostasis Mediates the Relationship Between Cardiorespiratory Fitness and Cognitive Speed in Aging Adults.

胰岛素稳态调节老年人的心肺健康和认知速度之间的关系。

• DOI: 10.3233/jad-221249
• 发表时间: 2023
• 期刊: Journal of Alzheimer's disease : JAD
• 作者: McIntyre,ClaytonC;Gaitán,JulianM;Edmunds,KyleJ;Lose,SarahR;Bendlin,BarbaraB;Sager,Mark;Asthana,Sanjay;Johnson,SterlingC;Okonkwo,OziomaC
• 通讯作者: Okonkwo,OziomaC