PET Measures of CSF Clearance in Preclinical Alzheimer's Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 116
- 试验地点
- 1
- 主要终点
- Percent change in brain amyloid
研究概览
简要总结
The purpose of this study is to measure cerebrospinal fluid (CSF) clearance. CSF cushions the brain from impact and carries waste products from the brain to the bloodstream. This process is known as clearance. Researchers have considered that impaired clearance of amyloid (a protein) from the aging brain causes buildup of amyloid in the brain and plays a role in increased risk for Alzheimer's disease. However, until recently, there has not been a method to measure CSF clearance. This study will examine CSF clearance using positron emission tomography (PET) scanning, which creates images of structures in the body and their functioning. This study will also measure the amount of two proteins, tau and amyloid, in the brain. Tau and amyloid are proteins that build up in the brains of people with Alzheimer's disease. An investigational compound (tracer) called [18F]MK-6240 is injected into the blood prior to the scan in order to take images of the CSF clearance and measure tau protein in the brain. This tracer is considered investigational because it is not approved by the US Food and Drug Administration (FDA) for clinical use and is only being used for research purposes.
详细描述
The impaired clearance of amyloid-β (Aβ) leading to the accumulation of Aβ plaques and consequent neurodegeneration, is a partially understood mechanistic hypothesis for late onset Alzheimer's disease (AD). Using Positron Emission Tomography (PET) and a tracer for tau lesions, with a low molecular weight that rapidly enters and clears the brain, the investigators developed, replicated, and validated a non-invasive method to estimate the clearance of CSF at ventricular and brain levels. The investigators propose to complete over five years, a 2y longitudinal study designed to test in preclinical AD the hypothesis that reduced CSF clearance measured with the tau tracer [18F]-MK6240 is predictive of: a) future amyloid lesions (PiB-PET or Florbetaben-PET); b) brain atrophy (MRI); and c) cognitive decline.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female subjects between 20-100 years old will be enrolled. Younger subjects are not included as the risk for brain amyloid lesions is too low
- •All subjects will speak English as their first language or demonstrate proficiency in English.
- •All subjects may have normal cognition or cognitive impairment.
- •All subjects will be in good general health and able to participate in the LP and imaging exams. This determination is made by the study neurologist and reviewed at a consensus meeting for each subject.
排除标准
- •Uncontrolled hypertension or metabolic disease
- •Neurodegenerative disorders (i.e. Parkinson disease. LBD, or FTD).
- •Long life major depression. Baseline scores ≥20 on Beck Depression Inventory at baseline
- •Long-life DSM-IV axis 1 disorders.
- •Mental retardation.
- •Substance abuse.
- •Concurrent medication limiting validity of neuropsychological tests or imaging.
- •Anti-depressants with anti-cholinergic properties
- •Monoamine oxidase inhibitors (MAOi)
- •Regular use of narcotic analgesics (>2 doses per week).
- •Use of neuroleptics
- •Individuals taking over the counter memory enhancing or protecting medications (e.g. ginkgo biloba, vitamins) are not excluded.
- •Implanted medical devices that are incompatible with MRI imaging.
- •Radiation exposures exceeding annual Rad Worker limits.
- •Heart failure stage D as defined by American Heart Association (7).
- •Chronic kidney disease in stages ≥ 4, as defined per National Kidney Foundation (8).
- •Brain tumor and other neoplastic disorders outside the brain where disease itself or its treatment (radiation, chemotherapy) is likely to affect brain structure or function.
- •Stroke when meeting criteria for total anterior, partial anterior or posterior circulation infarct according to the Oxford Community Stroke Project classification. Patients with clinically silent of lacunar strokes and transient ischemic attacks will not be excluded.
- •Significant head trauma.
- •Hydrocephalus.
- •Hostility or refusal to cooperate
- •Person's receiving chronic anti-coagulation therapy
- •Person's participating in other research projects will be excluded when the other project(s) 1) involve radiation exposure which in combination with the current project would increase radiation exposure above federal guidelines, 2) involve administration of study drug or other experimental therapy, or 3) prohibit participation in other research projects.
- •Participants in this study will be allowed to participate in other observational research studies. The investigators will review at enrollment the full array of projects a subject may be involved in and inform the other PI's to ensure that subject safety and research data integrity is not compromised.
结局指标
主要结局
Percent change in brain amyloid
时间窗: Baseline and 24 Months follow-up
Percent change in brain amyloid measured by positron emission tomography
Percent change in cortical ribbon thickness
时间窗: Baseline and 24 Months follow-up
Percent change in cortical ribbon thickness measured by magnetic resonance imaging
次要结局
未报告次要终点