Locus-coeruleus Function in Normal Elderly and AD Risk
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Percentage of Time Spent in REM Sleep
研究概览
简要总结
Growing evidence suggests that Alzheimer's disease (AD) pathological changes begin decades before clinical symptoms and tau abnormalities in the locus coeruleus (LC) can be observed since midlife. We have previously demonstrated functional vulnerability of the LC to aging and stress, as well as an association between higher cerebrospinal fluid (CSF) tau and impaired sleep phenomena influenced by the LC. We now aim to test whether LC dysfunction can be measured in preclinical AD stages by LC targeted imaging, and whether it objectively affects sleep architecture and attention. We will test this hypothesis in 30 cognitively normal older adults by performing a full clinical evaluation, one night of polysomnography, a lumbar puncture to obtain cerebrospinal fluid, [11C]MRB PET-MR, and attention testing. This study has the potential to identify a new mechanism by which tau pathology contributes to sleep and attention dysfunction and may provide a new therapeutic target for AD prevention.
详细描述
The purpose of this study is three-fold: to test whether lower NET availability in the LC is associated with: first, CSF tau levels typical of preclinical stages of AD (Aim 1); second, reduced REM and spindle density (Aim 2); and third, impaired performance on attention tasks (Aim 3). The goal is to test the overarching hypothesis that LC dysfunction occurs in preclinical AD stages, can be measured with MRB-PET, and translates into impairment of sleep architecture (LC tonic dysfunction) and attention (LC phasic dysfunction).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects with normal cognition and 55-75 years of age will be enrolled.
- •Subjects will be within normal limits on neurological and psychiatric examinations.
- •All subjects enrolled will have a CDR of
- •This will be evaluated through a clinical interview administered by a study physician (informant interview will not be required).
- •All subjects will have had a minimum of 12 years of education.
排除标准
- •History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, stroke, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
- •Significant history of alcoholism or drug abuse.
- •Significant history of psychiatric illness (e.g., schizophrenia, bipolar, PTSD, or life-long history of major depression).
- •Geriatric Depression Scale (short form)>
- •Insulin dependent diabetes.
- •Evidence of clinically relevant cardiac, pulmonary, endocrine or hematological conditions.
- •Physical impairment of such severity as to adversely affect the validity of psychological testing.
- •Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
- •History of a first-degree family member with early onset (age <60 years) dementia.
- •Irregular sleep-wake rhythms (based on the actigraphy recordings) or significant OSA (AHI4%≥15).
- •Taking Coumadin/warfarin and/or medications affecting cognition or sleep.
- •Failure to complete all study visit within 4 months
研究组 & 干预措施
Cognitively Normal (CN) Older Adults
干预措施: Nocturnal polysomnography (NPSG) (Procedure)
Cognitively Normal (CN) Older Adults
干预措施: Lumbar Puncture (LP) (Procedure)
Cognitively Normal (CN) Older Adults
干预措施: PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB) (Other)
Cognitively Normal (CN) Older Adults
干预措施: Psychomotor Vigilance Task (PVT) (Behavioral)
结局指标
主要结局
Percentage of Time Spent in REM Sleep
时间窗: Visit 3 (1-4 weeks after Visit 2)
REM sleep is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
REM Sleep Continuity
时间窗: Visit 3 (1-4 weeks after Visit 2)
Reported as percentage of REM runs that are less than 5, greater than or equal to 5 and greater than or equal to 10 minutes.
Mean Psychomotor Vigilance Test (PVT) Reaction Time
时间窗: Visit 3 (1-4 weeks after Visit 2)
PVT measures the reaction speed to a randomly time-occuring visual stimuli, allowing the assessment of several aspects of attention including response times, attention lapses and false starts.
Methylreboxetine (MRB)-LC Mean Standardized Uptake Value Ratio (SUVR) Values
时间窗: Visit 4 (1-4 weeks after LP)
Methylreboxetine (MRB)-LC Mean Standardized Uptake Value Ratio (SUVR) Values
时间窗: Visit 4 (1-4 weeks after LP)
Total Rapid Eye Movement (REM) Duration (Min)
时间窗: Visit 3 (1-4 weeks after Visit 2)
REM sleep is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
Percentage of Time Spent in REM Sleep
时间窗: Visit 3 (1-4 weeks after Visit 2)
REM sleep is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
REM Sleep Continuity
时间窗: Visit 3 (1-4 weeks after Visit 2)
Reported as percentage of REM runs that are less than 5, greater than or equal to 5 and greater than or equal to 10 minutes.
Number of sleep spindles that occur per minute during the N2 stage of sleep (N2 Spindle Density)
时间窗: Visit 3 (1-4 weeks after Visit 2)
N2 Spindle Density is derived from in-laboratory nocturnal polysomnography (NPSG) sleep study.
Mean Psychomotor Vigilance Test (PVT) Reaction Time
时间窗: Visit 3 (1-4 weeks after Visit 2)
PVT measures the reaction speed to a randomly time-occuring visual stimuli, allowing the assessment of several aspects of attention including response times, attention lapses and false starts.
Mean picture test response time
时间窗: Visit 3 (1-4 weeks after Visit 2)
The "Picture" test is used to measure the strength of the participants' memory by using a series of images. Before sleep, participants identify whether or not the image was inside or outside and whether or not the picture was emotional or neutral to them. After sleep, the participant will be shown images where some are new and some are old and asked whether or not they saw them before sleep. The images are selected from The International Affective Picture System.
Percentage of Correct Responses on the picture test
时间窗: Visit 3 (1-4 weeks after Visit 2)
The "Picture" test is used to measure the strength of the participants' memory by using a series of images. Before sleep, participants identify whether or not the image was inside or outside and whether or not the picture was emotional or neutral to them. After sleep, the participant will be shown images where some are new and some are old and asked whether or not they saw them before sleep. The images are selected from The International Affective Picture System.
次要结局
- Levels of Hyperphosphorylated Tau (P-Tau, T-Tau)(Visit 4 (1-4 weeks after LP))