Combined Aerobic Exercise and Cognitive Training for Alzheimer's Disease Prevention in At-Risk Seniors Estimated by An Exosomal Synaptic Protein Model: Cognition and Exosomal Synaptic Proteins Effects
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Change in cognitive function over time as assessed by Clinical Dementia Rating (CDR)
研究概览
简要总结
The study aims to investigate the effect of a long-term combined aerobic exercise and cognitive training program on cognitive function and blood exosomal synaptic protein levels in seniors at increased risk for Alzheimer's Disease.
详细描述
Alzheimer's disease (AD) is the most common cause of dementia in people older than 65 years worldwide. The neuropathological changes of AD occur decades before the onset of cognitive impairment, suggesting that early identification and timely intervention may postpone the clinical progress. In addition to its characteristic amyloid β and tau pathology, AD is also marked by synaptic dysfunction. Abnormal synaptic protein levels, such as growth associated protein 43 (GAP43), neurogranin, synaptotagmins, and synaptosome associated protein 25 (SNAP25) have been observed in the brain tissue and cerebrospinal fluid (CSF). Blood neuro-exosomal synaptic proteins have emerged as promising predictors for AD and cognitive decline. Particularly, the investigators previously reported a combination of blood neuro-exosomal protein (GAP43, neurogranin, SNAP25, and synaptotagmin 1) can predict AD 5 to 7 years before the clinical onset.
Both physical exercise and cognitive training have been demonstrated to improve cognitive function in AD and to exert a protective effect against developing dementia in the normal aging population. Furthermore, cognitive stimulation is an established modulator of synaptic plasticity and physical exercise might regulate synapse functional and structural change. However, whether cognitive training and physical exercise can alter exosomal synaptic protein levels and the relationship of biomarker changes to cognitive function in those seniors at increased risk for AD remain unclear.
In this study, the investigators aim to
- assess the effects of a long-term combined aerobic exercise and cognitive training program on cognitive function and the predictive biomarkers (blood neuro-exosomal synaptic proteins: GAP43, neurogranin, SNAP25, and synaptotagmin 1) in seniors at increased risk of AD with abnormally decreased levels of the biomarkers.
- determine the relationship of biomarker changes with cognitive function in these people.
- confirm the predictive value of the blood neuro-exosomal synaptic proteins for AD in a longitudinal setting.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mandarin-speaking subjects.
- •Not clinically demented.
- •Meeting the cutoff values of MMSE and CDR.
- •With low levels of blood neuro-exosomal synaptic proteins (GAP43<1983pg/ml, synaptotagmin 1<431pg/ml, neurogranin<1433pg/ml, SNAP25<448pg/ml)
- •Exclusion criteria:
- •Had major neurologic diagnosis (e.g., Alzheimer's disease, Parkinson's disease, stroke, encephalitis, and epilepsy) or other condition that might impair cognition or confound assessments.
- •Had a history of psychotic episodes or had major depression (Hamilton Depression Rating Scale score > 24 points).
- •Had severe systemic diseases, such as tumors, cardiovascular or orthopedic disorders that can affect the ability to perform the proposed intervention tasks.
排除标准
- 未提供
结局指标
主要结局
Change in cognitive function over time as assessed by Clinical Dementia Rating (CDR)
时间窗: baseline time, year 1, year 3, year 5, year 7
CDR will be performed to evaluate the cognition of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 18, with higher values indicating worse cognition.
Change in cognitive function over time as assessed by Trail-Making Test Parts A and B (TMT-A and TMT-B)
时间窗: baseline time, year 1, year 3, year 5, year 7
TMT-A and TMT-B will be performed to evaluate the executive function of participants at the enrollment and year 1, year 3, year 5, year 7. Scoring is based on time taken to complete the test (e.g., 35 seconds yielding a score of 35), with lower scores indicating better cognition.
Change in cognitive function over time as assessed by the Rey-Osterrieth Complex Figure Test (ROCF)
时间窗: baseline time, year 1, year 3, year 5, year 7
ROCF will be performed to evaluate the visuospatial function and other cognition domains of participants at the enrollment and year 1, year 3, year 5, year 7. Participants are asked to produce a complicated line drawing, with higher scores indicating better cognition.
Change in cognitive function over time as assessed by Boston Naming Test (BNT)
时间窗: baseline time, year 1, year 3, year 5, year 7
BNT will be performed to evaluate the language function of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 30, with higher values indicating better cognition.
Change in cognitive function over time as assessed by California Verbal Learning Test (CVLT)
时间窗: baseline time, year 1, year 3, year 5, year 7
CVLT will be performed to evaluate the memory function of participants at the enrollment and year 1, year 3, year 5, year 7. Participants are asked to finish immediate recall, delayed recall, and delayed recognition tasks in the test, with higher scores indicating better cognition.
Change in cognitive function over time as assessed by the Montreal Cognitive Assessment (MoCA)
时间窗: baseline time, year 1, year 3, year 5, year 7
MoCA will be performed to evaluate the cognition of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 30, with higher values indicating better cognition.
Change in cognitive function over time as assessed by Verbal Fluency Test
时间窗: baseline time, year 1, year 3, year 5, year 7
Verbal Fluency Test will be performed to evaluate the semantic memory function of participants at the enrollment and year 1, year 3, year 5, year 7. Participants are asked to produce as many animals as possible within 1 minute. The score is the number of animals, with higher scores indicating better cognition.
Change in cognitive function over time as assessed by Mini Mental State Examination (MMSE)
时间窗: baseline time, year 1, year 3, year 5, year 7
MMSE will be performed to evaluate the cognition of participants at the enrollment and year 1, year 3, year 5, year 7. The score ranges from 0 to 30, with higher values indicating better cognition.
Change in cognitive function over time as assessed by Digit Span Test-Forward and Backward
时间窗: baseline time, year 1, year 3, year 5, year 7
Digit Span Tests will be performed to evaluate the working memory of participants at the enrollment and year 1, year 3, year 5, year 7. The total scores are twelve for each test, with higher values indicating better cognition.
次要结局
- Changes in concentrations of blood neuro-exosomal synaptotagmin1 over time(baseline time, year 1, year 3, year 5, year 7)
- Changes in concentrations of blood neuro-exosomal GAP43 over time(baseline time, year 1, year 3, year 5, year 7)
- The area under curve of the blood neuro-exosomal synaptic proteins (GAP43, neurogranin, SNAP25, and synaptotagmin1) for the accurate diagnosis of AD(up to 7 years)
- Changes in concentrations of blood neuro-exosomal neurogranin over time(baseline time, year 1, year 3, year 5, year 7)
- Changes in concentrations of blood neuro-exosomal SNAP25 over time(baseline time, year 1, year 3, year 5, year 7)