Neuroactive Steroids and Cognition in Humans: Pregnenolone Sulfate an Early Marker of the Memory Loss Associated With Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 90
- 试验地点
- 6
- 主要终点
- Plasma concentrations of PREGS determined by GC-MS
研究概览
简要总结
The steroid pregnenolone sulfate (PREGS) may be one of the factors responsible for the memory decline related to normal aging or associated with Alzheimer's disease (AD). The purpose of this study is to determine whether plasma levels of PREGS are decreased patients with at mild to moderate AD compared with AD-free control subjects matched for gender and age and to see whether they are inversely correlated with the severity of memory deficits in AD patients. The hypothesis is that blood levels of PREGS are decreased with advanced age and with the stage of AD that would be positively correlated with memory deficits. Therefore PREGS could be considered as an early marker of the memory deficits in AD.
详细描述
PREGS is a derivative of pregnenolone which the obligatory precursor of all steroid hormones originating from the gonads and adrenal glands. In rodents, PREGS has been demonstrated to improve memory performance in various behavioural tests. In humans, PREGS is one the most abundant circulating steroids. There are some indications about its decrease in blood during aging, and in brain samples from aged patients with AD, low concentrations of PREGS have been correlated with high levels of beta-amyloid peptide and phosphorylated tau protein. To date, a precise and rigorous evaluation of PREGS blood concentrations during aging is lacking and the relationship between these concentrations and the memory loss associated with AD has not been established.
Primary objective To show that plasma concentrations of PREGS are decreased in AD patients (" case ") compared to free-AD subjects (" controls "), matched for gender and age.
Secondary objectives
- To show that plasma concentrations of PREGS are inversely correlated with the severity of memory deficits in AD patients.
- To show that plasma concentrations of PREGS are correlated with the memory scores in the controls.
- To show that plasma concentrations of PREGS decrease in the controls.
- To search for a relationship between some of PREGS metabolites and age or the severity of memory deficits.
This is a case-control study that will comprise 200 subjects aged over 70 years, including 100 outpatients with mild to moderate AD and 100 AD-free volunteer controls matched on age and gender. These two groups will be stratified into age-sub-groups [70-74] [75-79] [80-84] [85-89] > 90 years and will include 10 men and 10 women per sub-group.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects aged over 70 years who have signed informed consent for participation to the study and are affiliated to a social security regimen.
- •For patients: subjects with probable AD according to the DSM-IV criteria and the NINCDS/ADRDA criteria and with mild to moderate probable AD: MMSE score>
- •For Controls: subjects without cognitive deficits on neuropsychological tests: scores of MMSE > 26 and of the 5 Word test equal to 10/10 and of the Clock Drawing test equal to 7/7.
排除标准
- •Guardianship
- •History of cerebrovascular disease, Parkinson's disease, other known dementia, epilepsy
- •Major depression
- •Serious sensory disorders; deficits in language & comprehension
- •Serious heart or hepatic insufficiencies, renal or respiratory failures
- •Unstable diabetes or endocrine disorders, thyroid dysfunction, cancer, inflammatory syndrome, malnutrition
- •Cognitive training during the 6 previous months
- •Medications: steroids (HRT, androgens, corticoids), anti-depressants, cholinesterase inhibitors, thyroid hormones, synthetic anti-thyroids
- •Contraindications for MRI: metallic implants & claustrophobia
结局指标
主要结局
Plasma concentrations of PREGS determined by GC-MS
时间窗: At the day of diagnostic blood collection
次要结局
- Memory scores of the RL-RI test according to the GROBER and BUSCKE test(At the day of blood collection)
- Plasma concentrations of PREGS metabolites(At the day of blood collection)