Questionable Dementia: Course and Predictors of Outcome

可疑痴呆症：病程和结果预测因素

• 批准号: 7618382
• 负责人: DAVANGERE P DEVANAND
• 金额: $ 83.77万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7618382
• 关键词: AD 41; Age; Algorithms; Apolipoprotein E; Atrophic; Attention; Brain; Brain imaging; Clinical; Clinical Trials; Cognitive; Data; Dementia; Digit structure; Early treatment; Ensure; Evaluation; F2-Isoprostanes; Family Planning; Functional disorder; Future; Genotype; Goals; Head; Hippocampus (Brain); Imaging Techniques; Impaired cognition; Impairment; Magnetic Resonance Imaging; Measures; Medial; Memory impairment; Metabolism; Methods; Neuropsychological Tests; Noise; Odors; Outcome; Patient Selection; Patients; Pattern; Pittsburgh Compound-B; Positron-Emission Tomography; Procedures; Public Health; ROC Curve; Recruitment Activity; Reporting; Sampling; Sampling Studies; Sex Education; Signal Transduction; Smell Perception; Spinal Puncture; Testing; Visit; amyloid imaging; base; clinical application; cohort; executive function; fluorodeoxyglucose positron emission tomography; follow-up; functional disability; improved; informant; innovation; meetings; mild neurocognitive impairment; neuropsychological; novel; older patient; processing speed; sex; single photon emission computed tomography; tau Proteins; tau-1; uptake

DESCRIPTION (provided by applicant): In R01AG17761, 150 patients with mild cognitive impairment (MCI) and 63 age and sex-matched healthy control subjects are followed. With an average of 5 years' follow-up, specific neuropsychological test scores, odor identification deficits, patient-informant discrepancy in report of function, MRI hippocampal and entorhinal atrophy are highly significant predictors of conversion to AD (41 converters to date), apolipoprotein E e4 genotype is significant only in older patients, and SPECT medial temporal and posterior cingulate deficits are significant only in some analyses. Selective Reminding Test delayed recall, odor identification deficits, hippocampal volume, and entorhinal volume are the variables identified for the initial algorithm to predict MCI conversion to AD. This head-to-head comparison of predictors, and the initial predictive algorithm for MCI conversion to AD, are novel and unique, and have potential clinical impact. Completion of 9-year follow-up is needed to accurately identify all MCI converters to AD, and to improve accuracy for evaluation of the hypothesized predictors and the predictive algorithm. In order to achieve eventual clinical application, it is critical to build upon the ongoing study's findings by enhancing the signal to noise ratio, improving predictive accuracy by modifying and expanding specific assessments, and independently validating the findings in a new sample. Therefore, in a new study, 140 patients with amnestic MCI (with or without other cognitive domain deficits) and 50 control subjects will be recruited and systematically followed to test new potential predictors of MCI conversion to AD. These include more sensitive and specific cutting-edge brain imaging techniques that should enhance signal to noise ratio and predictive accuracy: improved structural MRI, [18F]-FDG, and p-amyloid imaging with [11C]-6-OH-BTA-1 (Pittsburgh compound B). New [11C]-6-OH-BTA-1 PET pilot data are very promising. Informant report of cognitive decline will be added, and the functional, olfactory and neuropsychological predictors will be modified and improved. In subjects who agree to lumbar puncture, CSF tau, phosphorylated tau (P- tauisi), AB42 and F2-isoprostanes will be assessed at baseline. The primary analyses in the new study will be restricted to the new study sample. Before combining the amnestic MCI patients across the two samples to generate the predictive algorithm for predictors common to the two studies, we will rediagnose the ongoing study sample's follow-up visits using the improved new study methods, ensure comparability in demographics/clinical features, and require that specific predictor by sample interaction criteria be met. Relevance. There are several clinical and public health implications. Accurate prediction of MCI conversion to AD will help identify patients who need early treatment, facilitate patient/family planning for their own future, and improve patient selection for clinical trials.

描述（由申请人提供）：在R01AG17761中，遵循150例轻度认知障碍（MCI）和63岁和性匹配的健康对照组患者。平均进行5年的随访，特定的神经心理测试评分，气味识别缺陷，功能报告中的患者形式差异，MRI海马和内himbocampal和内haporhinal萎缩是高度重要的预测指标，这是AD转化的高度重要预测指标（迄今为止41个转化器）仅在某些apolipopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopopotion e e4基因中显着，并且在某些e4基因中均具有重要的差异。分析。选择性提醒测试的延迟召回，气味识别缺陷，海马体积和内hinal量是初始算法确定的变量，以预测MCI转换为AD。预测因子的正面比较以及MCI转化为AD的初始预测算法是新颖而独特的，并且具有潜在的临床影响。需要完成9年随访的完成，以准确识别所有MCI转换器到AD，并提高评估假设的预测因子和预测算法的准确性。为了实现最终的临床应用，至关重要的是，通过提高信号与噪声比，通过修改和扩展特定评估并独立验证新样本中的发现来建立正在进行的研究的发现，从而提高预测精度。因此，在一项新研究中，将招募140名具有Amnescic MCI（或没有其他认知领域缺陷的患者（有或没有其他认知领域缺陷），并系统地遵循50名对照对象，以测试MCI转化为AD的新潜在预测指标。这些包括更灵敏，更特定的尖端脑成像技术，这些技术应提高信号与噪声比和预测精度：改善结构MRI，[18F] -FDG和P-淀粉样蛋白成像，并使用[11C] -6-OH-BTA-1（Pittsburgh Amp）（Pittsburgh Amp）。新的[11C] -6-OH-BTA-1 PET PILOT数据非常有前途。将添加有关认知能力下降的线人报告，并将修改和改进功能，嗅觉和神经心理学预测因子。在同意腰椎穿刺的受试者中，CSF TAU，磷酸化tau（p-tauisi），AB42和F2-异前鸟将在基线时进行评估。新研究中的主要分析将仅限于新研究样本。在将两种样品中的羊膜MCI患者相结合以生成针对这两项研究常见的预测因子的预测算法之前，我们将使用改进的新研究方法重新诊断正在进行的研究样本的后续访问，确保人口统计学/临床特征的可比性，并符合样本交互标准的特定预测。关联。有几种临床和公共卫生的影响。准确预测MCI转换为AD，将有助于确定需要早期治疗的患者，促进患者/计划生育自己的未来，并改善患者选择临床试验。