Robust detection of atrophy over short intervals in AD and FTLD

在 AD 和 FTLD 中短时间间隔内对萎缩进行稳健检测

• 批准号: 10633960
• 负责人: BRADFORD C DICKERSON
• 金额: $ 83.47万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10633960
• 关键词: Acceleration; Alzheimer' s Disease; Amyloid; Anatomy; Atrophic; Biological; Biological Markers; Brain; Brain region; Brain scan; Cessation of life; Clinical; Clinical Trials; Clinical Trials Design; Cross-Over Trials; Data; Dementia; Detection; Diagnosis; Disease; Early Onset Alzheimer Disease; Family; Foundations; Frontotemporal Lobar Degenerations; Goals; Individual; Investigation; Knowledge; Lobar; Location; MRI Scans; Magnetic Resonance Imaging; Maps; Measurable; Measurement; Measures; Methodology; Methods; Monitor; Multicenter Studies; Natural History; Nerve Degeneration; Neurodegenerative Disorders; Outcome; Participant; Patients; Persons; Positron-Emission Tomography; Public Health; Research; Running; Sample Size; Sampling; Scanning; Site; Structure; Syndrome; Techniques; Technology; Therapeutic Trials; Thick; Time; Validity and Reliability; Work; behavioral variant frontotemporal dementia; brain cell; brain magnetic resonance imaging; brain size; brain volume; cerebral atrophy; early onset; fluorodeoxyglucose positron emission tomography; imaging facilities; improved; in vivo; interest; neurodegenerative dementia; novel; novel strategies; phase III trial; regional atrophy; scale up; standard measure; tau Proteins; time interval; trial design

PROJECT SUMMARY Alzheimer’s disease, Frontotemporal Lobar Degeneration, and other diseases that lead to dementia are one of the 21st century’s major public health problems. This family of neurodegenerative diseases involves the disruption of functional brain circuits and ultimately the death of brain cells. In living people, the standard measure of neurodegeneration is derived from brain MRI scans, which can quantitatively measure the location and amount of atrophy. This is traditionally done, and continues to be done in many studies, over intervals of one year, with one or two scans collected one year apart, estimating annualized rates of brain atrophy. In some clinical trials, scans may be collected more frequently, but in one recent failed phase III trial aiming to slow neurodegeneration they were collected 80 weeks apart. The goal of this work is to demonstrate that new methods we and our colleagues have developed are able to improve the sensitivity to detect atrophy within individuals over short intervals of time, down to as little as 3 months. This is done by making a large number of extremely fast, highly precise repeated measurements at each time point for each individual. We aim to demonstrate the reliability and validity of these new MRI measures of neurodegeneration against traditional MRI measures and externally validated against PET and clinical measures in individuals with Early-onset Alzheimer’s disease or behavioral variant Frontotemporal Dementia. If successful, this work could revolutionize the field and open the door to a new means to track neurodegeneration, potentially greatly facilitating clinical trials.

项目概要 阿尔茨海默病、额颞叶变性和其他导致痴呆的疾病是其中之一 21 世纪的主要公共卫生问题涉及神经退行性疾病。 在活人中，功能性脑回路的破坏并最终导致脑细胞死亡。 神经退行性变的测量源自大脑 MRI 扫描，可以定量测量位置 这是传统上进行的，并且在许多研究中持续进行，每隔一段时间进行一次。 一年，间隔一年收集一次或两次扫描，估计某些人的脑萎缩年率。 临床试验中，扫描可能会更频繁地收集，但在最近一项失败的 III 期试验中，旨在减缓 它们是在相隔 80 周时收集的。这项工作的目标是证明这一新发现。 我们和我们的同事开发的方法能够提高检测内萎缩的灵敏度 个体在较短的时间间隔内（短至 3 个月）这是通过大量生产来完成的。 我们的目标是在每个时间点对每个人进行极其快速、高精度的重复测量。 证明这些新的神经退行性 MRI 测量相对于传统方法的可靠性和有效性 早发型患者的 MRI 测量以及针对 PET 和临床测量的外部验证 阿尔茨海默病或行为变异额颞叶痴呆如果成功，这项工作可能会带来革命性的变化。 该领域并为追踪神经退行性变的新方法打开了大门，可能极大地促进临床 试验。