Identification of Neuroinflammation and Neuroimaging Biomarkers Through Data Driven Artificial Intelligence Techniques for Unraveling the Heterogeneity of Aged Subjects at Risk of Dementia and to Better Inform Prevention Strategies
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 115
- 试验地点
- 1
- 主要终点
- Short term training effects
研究概览
简要总结
SCD and MCI are very heterogeneous conditions, which can be prodromal to different types of dementia. The application of data driven clustering methods on neuroimaging and inflammatory data aims at identifying the features characterizing subgroups of subjects at high risk of developing overt dementia. This approach promises to develop tailored early interventions for subjects with profiles of cognitive decline correlating with high risk of progression. To this end in this project, we propose to examine in these subjects both brain structure and cerebral blood flow (CBF) through MR T1-weighted and pCASL (pseudo-continuous arterial spin labeling) imaging and the neuroinflammatory status. The latter will be done by measuring the populations of innate and adaptive immune cells, the chemokines that are required to attract these cells to their potential sites of action in the CNS, and the cytokines by means they exert their function. The analyses performed in aged subjects with MCI and in SCD, will allow identifying common mechanisms predisposing to an increased susceptibility to progression to overt cognitive decline.
详细描述
The recruitment will involve 35 MCI in the training cohort, 35 MCI in the placebo cohort and 75 SCD subjects.
Cognitive assessment: A comprehensive battery of neuropsychological tests will assess performance in memory, attention and executive function domains. For all MCI subjects the same cognitive assessment will be performed at the beginning of the study (T0), after 7 months (T7) and after 14 months (T14). SCD subjects will perform the cognitive assessment at T0, T7, T14 and after 28 months (T28), depending on the assigned arm.
Instrumental assessment: for all MCI subjects the instrumental assessment, MR brain scans (T1-weighted and pCASL), will be performed at T0 and at T7. 35 SCD subjects will be subjected to the instrumental assessment at T0 and at T28.
Blood samples: Blood samples for peripheral blood mononuclear cell (PBMC) isolation will be withdrawn from all MCI and SCD subjects, at baseline. For all MCI patients blood samples will be taken also at T7 and T14, for SCD subjects also at T28. Cellular mediators will be assessed by Flow cytometry analysis of monocyte/macrophage, T cell (CD3/CD4/CD8) and regulatory T cell (CD4+CD25+IL7Rlo). Serum/plasma will be prepared and stored for determination of soluble immune mediators of inflammation. ELISA determinations will be performed for IFNgamma, IL12, TNFalpha, IL-6, CCL2 and BDNF.
Intervention: After baseline assessment the MCI-training and SCD-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; while, the MCI-no training and SCD no-training will be followed in their natural history. According to the TtB protocol (Train the Brain Consortium, 2017) enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 month. The cognitive training programme will be based on 8 cycles composed by 18 sessions of exercises and activities aimed at stimulating multiple cognitive functions. Each cycle will last 3 weeks, after which the same kind of cognitive stimulation sessions will be restarted, with exercises and activities of increased complexity. Each cycle will be structured in sessions aimed at stimulating specific cognitive domains and in sessions focused on multimodal activities. The physical training will include aerobic exercise on an ergometer cycle, whose duration will be increased gradually from 10 to 20 minutes followed by exercises targeted to improve muscle strength, physical function, neuromuscular control and flexibility.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 89 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age between 65 and 89 years; 5 years of schooling;
- •diagnosis of Mild Cognitive Impairment (Croisile et al., 2011) or
- •diagnosis of Subjective Cognitive Decline (Jessen et al., 2014).
排除标准
- •neurological pathologies; dementia;
- •psychiatric disorders;
- •pathologies or orthopedic problems limiting participation to the aerobic physical training program and to the MR imaging.
研究组 & 干预措施
SCD no-training
Follow up of natural history of subjects after 7 months
MCI training
After baseline assessment the MCI-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; Enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 months.
干预措施: Multidomain cognitive training and physical training (Other)
MCI no-training
Follow up of natural history of subjects after 7 months
healthy subjects
Follow up of natural history of subjects after 7 months
SCD
Follow up of natural history of subjects after 28 months
SCD training
After baseline assessment the MCI-training group will receive a 7 months-long multidomain training, including cognitive, physical exercise and music therapy; Enrolled subjects will be assigned to mixed-gender classes of maximum 10 subjects each and given 2 sessions of 60 minutes supervised cognitive training per day, 3 times a week, and one of 60 minutes supervised aerobic physical activity per day, 3 times a week for 7 months.
干预措施: Multidomain cognitive training and physical training (Other)
结局指标
主要结局
Short term training effects
时间窗: 7 months
The MCI-training and MCI-no training, the SCD-training and SCD-no training groups will be compared at T7 in terms of cognitive performances, CBF, gray matter atrophy (both CBF and GM atrophy will be evaluated on different regions of interest) and inflammatory markers.
次要结局
- Sample stratification(7, 14 and 28 months)
研究者
Paolo Bosco
PhD
IRCCS Fondazione Stella Maris