Evaluation of Cerebrovascular Reactivity in Alzheimer's Disease Patients : A Pilot Clinical Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Cerebrovascular reactivity during the CO2 inhalation test in AD patients and control subjects (SCI)
研究概览
简要总结
The etiology of Alzheimer's disease (AD), the most common type of dementia, remains largely undefined and the early diagnostic and effective treatments are still not available. In addition to the neuropathological hallmarks, cerebrovascular dysfunction has been identified as an important component of AD. Using the experimental models, we showed that cerebrovascular reactivity (CVR), the ability of cerebral vessels to dilate or constrict in response to stimuli, is impaired very early in AD. We designed this trial to compare CVR to carbon dioxide (CVR CO2) in AD patients and in persons with subjective cognitive impairment (SCI), the cognitively healthy individuals which began to worry about worsening their memory, and to correlate CVR CO2 with AD markers in cerebrospinal fluid and the blood markers of endothelial function. We hypothesize that CVR represents a potential diagnostic/prognostic marker and an attractive target for the development of new therapeutics in AD.
详细描述
The primary objective of this study is to determine, whether the measurement of CVR CO2 makes it possible to differentiate AD patients from control SCI subjects (subjects with a memory complaint but without cognitive impairment as assessed with neuropsychological tests).
We also pursue the following secondary objectives:
- Establish correlations between cognitive level and CVR CO2 in the 2 groups: SCI and AD.
- Investigate a correlation between CVR CO2 and AD markers in cerebrospinal fluid
- Assess the correlation between cognitive function (Z score of neuropsychological tests) and CVR CO2.
- Look for a correlation between CVR CO2 and plasma levels of markers of endothelial function: endothelin-1 (ET-1), big-ET-1, asymmetric dimethylarginine (ADMA) as well as plasma renin activity.
We plan to enroll a total of 24 male and/or female patients (> 18 years) with a diagnosis of AD (group AD) and 24 male and/or female SCI subjects (> 18 years) which came to our hospital for consultation about poor memory function.
Each patient will be informed on the study protocol during his / her regular follow-up visit at Broca hospital's day clinic. Informed consent/assent will be obtained from each subject or his/her representative prior to conducting any study related procedures.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years and more
- •Alzheimer's disease as defined by the established clinical consensus criteria (DSM IV-TR and NINCDS-ADRDA) or
- •Subjective cognitive impairment: subjects who consulted for cognitive complaint without cognitive impairment on neuropsychological tests defined by normal cognitive scores located between - 1.5 and + 1.5 standard deviations (σ) compared to the average of subjects in their reference group (same age, same socio-educational level) and normal performances according to daily life activities scores.
排除标准
- •Non-Alzheimer's dementia (vascular dementia, Lewy body dementia, fronto-temporal dementia, dementia linked to Parkinson's disease and other)
- •Other diseases that may interfere with cognitive performance evaluation (severe depression, epilepsy, Parkinson's disease, psychosis, bipolar syndrome)
- •Active smoking
- •Uncontrolled hypertension (PAS / PAD> 140/90 mmHg despite correctly dosed antihypertensive therapy)
- •Heart failure
- •Recent myocardial infarction
- •Stenosis of the carotid commune or interne with plaque > 20%
- •Cerebrovascular lesions on MRI (major white matter lesions Fazekas 3,> 2 deficiencies and sequelae of cerebral infarction)
结局指标
主要结局
Cerebrovascular reactivity during the CO2 inhalation test in AD patients and control subjects (SCI)
时间窗: Up to 2 months
Cerebrovascular reactivity during the CO2 inhalation test in AD patients and control subjects (SCI), determined from the measurements of blood flow in the internal and commun carotid arteries. Subjects will be screened and if applicable for the study will be scheduled for a Doppler ultrasonography. At the second visit they will complete Doppler ultrasonography measurements.
次要结局
- Plasma levels of ET-1, bigET-1, ADMA and their correlation with CVR CO2(Up to 2 months)
- Z score of neuropsychological tests and CVR CO2(Up to 2 months)
- Correlation between cognitive status and différences in CVR CO2(Up to 2 months)
- Plasma renin activity and CVR CO2.(Up to 2 months)
- Correlation between cerebrospinal AD markers and CVR CO2(Up to 2 months)