Train the Brain - Effective of Cognitive and Physical Training in Slowing Progression to Dementia: a Clinical and Experimental Study
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 160
- 试验地点
- 2
- 主要终点
- Rate of cognitive decline, measured as score in neuropsychological tests
研究概览
简要总结
Train The Brain is aimed at assessing the efficacy of cognitive and physical training in slowing progression to dementia in patients diagnosed with mild cognitive impairment (MCI).
详细描述
Train The Brain is a clinical and experimental study on the effectiveness of cognitive and physical training in slowing progression to dementia, and on the relationship between (changes in) mental and cardiovascular fitness.
Cognitive decline due to ageing is becoming a major clinical and economic issue. Italy has 700,000 patients with dementia and 100,000 new cases are detected every year. Most common causes of dementia are Alzheimer's Disease (AD) and vascular dementia (VD). No treatment is available for the two conditions: drugs currently used are poorly effective and do not prevent, heal, stop, or delay the progression of the disease. It is therefore crucial to find interventions to counteract and slow cognitive decline from an early stage. A combined physical and cognitive training could convey benefits. Several studies have shown that both the strengthening of social and cognitive abilities and physical exercise do exert a positive effect on brain function in the elderly, and they reduce the risk of developing dementia by 20-50%; experimental studies on animal models support these findings, and also show a reversion of cognitive decline. On the other hand, controlled intervention studies on human beings are few and show methodological limitations. It is now established that subclinical cerebral alterations, detectable with structural and functional neuroimaging, appear well before clinical disease occur; this is called "Mild Cognitive Impairment" (MCI) and dramatically raises the risk of developing dementia in comparison to individuals without MCI. In this condition, a progressive decrease of the number and quality of synaptic connections in specific areas of the brain has been hypothesized; interventions aimed at counteracting the decrease in synaptic function and density, augmenting neural plasticity and the development and sparing of mnemonical circuits, could slow the progression to overt dementia. An early detection of cognitive impairment could allow to exploit the residual plasticity of the nervous system through therapeutic/rehabilitative interventions. The working hypothesis for this project is that physical and cognitive stimulation could positively affect cognitive decline in subjects at risk for dementia or with dementia at its early stage. This could delay the loss of self-sufficiency, therefore improving quality of life both for the patient and his caregivers with a safe and relatively cheap intervention, also reducing direct and indirect costs for caregiving for the families and the National Health Service.
The present study is interventional, in parallel groups with random allocation:
- Baseline evaluation; allocation to intervention or control;
- Measurement of brain volumetry and function; cardiovascular assessment;
- Intervention, or usual care for the control group;
- Evaluation after 7 months of intervention and 7 months after the completion.
Symptoms will be identified with an advanced set of diagnostic tests. In perspective, the aim is to develop a non-pharmacologic therapeutic strategy, which could be easily applied in the clinical practice by the structures of the National Health Service. The presence of a protocol of physical training allows also to improve knowledge about the relationship between cardiovascular and cerebral fitness in conditions of cognitive decline, an aspect virtually unexplored and absent from the current medical literature. Recent studies highlight that vascular damage and systolic hypertension in MCI subjects represent a risk factor for progression into overt AD, but also suggest that these alterations are an ideal target for secondary prevention. When the study is completed, it will be possible to discern if the chosen program of physical exercise and cognitive stimulation has been able to reduce, to a statistically significant degree, the progression of cognitive decline, as measured with neuropsychological tests, and brain damage, evaluated with morpho-functional techniques, in subjects with AD/VD in the intervention arm as compared to a control group. If this is the case, the combined physical/cognitive intervention procedure will be proposed as non-pharmacological preventive and therapeutic strategy. A final follow-up evaluation, seven months after the end of the intervention, will provide information about the duration of the effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Outcomes Assessor)
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
- 否
入选标准
- •Age between 65 and 89
- •Successful completion of primary school
- •MCI, as Mini Mental State Examination score between 20 and 27 and confirmation through neuropsychological examination by a specialist, according to current guidelines.
排除标准
- •Moderate/severe dementia
- •Clinical signs of depressive disorder or other primary psychiatric disorders
- •Neoplastic diseases
- •Neurologic or musculoskeletal deficits barring neuropsychological examination or physical or cognitive training
- •Severe heart disease
- •End stage renal disease (eGFR<35 ml/min(1.73 m2)
- •Severe chronic obstructive pulmonary disease (COPD) and/or respiratory failure
- •Complicated or decompensated diabetes
- •Overt peripheral artery disease
- •Any inability to successfully complete a brain magnetic resonance scan
- •Epilepsy, drug addiction
- •Current acute diseases or recent head trauma
结局指标
主要结局
Rate of cognitive decline, measured as score in neuropsychological tests
时间窗: 1) Baseline; 2) After seven months of intervention/control;3) Seven months after completion of intervention/control.
次要结局
- Recovery of normal frequency spectra in the electroencephalographic signal(1) Baseline; 2) After seven months of intervention/control; 3) Seven months after completion of intervention/control.)
- Rate of loss of grey and white matter in the cortex and the hippocampus, measured through Magnetic Resonance Imaging.(1) Baseline; 2) After seven months of intervention/control; 3) Seven months after completion of intervention/control.)
- Modifications in brain activation during cognitive tasks, measured through functional magnetic resonance imaging(Time Frame: 1) Baseline; 2) After seven months of intervention/control; 3) Seven months after completion of intervention/control.)
- Improvement in vascular function and structure, as variations in Flow Mediated Dilation, carotid intima-media thickness, arterial stiffness(1) Baseline; 2) After seven months of intervention/control; 3) Seven months after completion of intervention/control.)
- Variations in brain vascular reactivity as flow and diameter response to CO2 inhalation(1) Baseline; 2) After seven months of intervention/control; 3) Seven months after completion of intervention/control.)
研究者
Eugenio Picano
MD,PhD
Fondazione C.N.R./Regione Toscana "G. Monasterio", Pisa, Italy