Predicting future rates of tau accumulation on PET.
Predicting future rates of tau accumulation on PET.
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DOI：
10.1093/brain/awaa248
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发表时间：
2020-10-01
期刊：
影响因子：
--
通讯作者：
Petersen RC
中科院分区：
文献类型：
--
作者：
Jack CR;Wiste HJ;Weigand SD;Therneau TM;Lowe VJ;Knopman DS;Botha H;Graff-Radford J;Jones DT;Ferman TJ;Boeve BF;Kantarci K;Vemuri P;Mielke MM;Whitwell J;Josephs K;Schwarz CG;Senjem ML;Gunter JL;Petersen RC
Jack等人表明，在认知未受损的个体中，高tau PET累积率的唯一独立预测因子是淀粉样变性。在认知受损的个体中，与早发性阿尔茨海默病表型一致的变量预测tau PET累积的速率较高。抗tau药物的临床试验需要针对有tau积累风险的个体。我们的目标是确定研究环境中可用的变量，这些变量分别预测认知未受损或认知受损的个体中tau PET累积的未来速率。所有337名参与者都有：基线研究访视，包括MRI、淀粉样蛋白PET和tau PET检查，至少一次随访tau PET检查;并符合两个临床诊断组之一的临床标准：认知未受损（n = 203）;或认知受损（n = 134，轻度认知障碍或痴呆伴阿尔茨海默氏临床综合征的参与者组合组）。我们的主要分析是在这两个临床组中进行的;然而，我们还评估了按正常/异常淀粉样蛋白PET划分的未受损组和按临床表型（轻度认知障碍、遗忘性痴呆和非遗忘性痴呆）划分的受损组的亚组。采用线性混合效应模型评估年龄、性别、教育程度、APOE基因型、淀粉样蛋白和tau PET标准化摄取值比值（SUVR）、认知能力、皮质厚度和基线时的白色高信号体积以及随后的tau PET蓄积率之间的相关性。将对数转换的tau PET SUVR用作应答，并将速率总结为年度百分比变化。使用颞叶tau PET元感兴趣区域。在认知未受损组中，只有较高的基线淀粉样蛋白PET是较高tau积聚率的显著独立预测因子（P < 0.001）。在淀粉样蛋白PET异常的认知未受损亚组中，tau蛋白累积率较高与认知下降率较快相关（P = 0.03），但在淀粉样蛋白PET正常的亚组中。在认知受损组中，年龄较小（P = 0.02）、基线淀粉样蛋白PET（P = 0.05）、APOE ε4（P = 0.05）较高和认知能力较好（P = 0.05）是tau蓄积率较高的显著独立预测因素。在受损个体中，更快的认知能力下降与更快的tau蛋白积累速率相关（P = 0.01）。虽然我们检查了许多可能的预测变量，但我们的结果表明，筛选未受损个体以纳入抗tau试验可能是简单的，因为高tau比率的唯一独立预测因素是淀粉样变性。在认知障碍个体中，与早发性阿尔茨海默病表型一致的成像和临床变量与较高的tau PET累积率相关，这表明这可能是一个非常有利的群体，可以在其中进行针对tau相关机制的概念验证临床试验。痴呆表型的性质（遗忘型与非遗忘型）并不影响这一结论。
Jack et al. show that in cognitively unimpaired individuals, the only independent predictor of high tau PET accumulation rates is amyloidosis. In cognitively impaired individuals, variables that are consistent with an early-onset Alzheimer’s disease phenotype predict higher rates of tau PET accumulation. Clinical trials with anti-tau drugs will need to target individuals at risk of accumulating tau. Our objective was to identify variables available in a research setting that predict future rates of tau PET accumulation separately among individuals who were either cognitively unimpaired or cognitively impaired. All 337 participants had: a baseline study visit with MRI, amyloid PET, and tau PET exams, at least one follow-up tau PET exam; and met clinical criteria for membership in one of two clinical diagnostic groups: cognitively unimpaired (n = 203); or cognitively impaired (n = 134, a combined group of participants with either mild cognitive impairment or dementia with Alzheimer’s clinical syndrome). Our primary analyses were in these two clinical groups; however, we also evaluated subgroups dividing the unimpaired group by normal/abnormal amyloid PET and the impaired group by clinical phenotype (mild cognitive impairment, amnestic dementia, and non-amnestic dementia). Linear mixed effects models were used to estimate associations between age, sex, education, APOE genotype, amyloid and tau PET standardized uptake value ratio (SUVR), cognitive performance, cortical thickness, and white matter hyperintensity volume at baseline, and the rate of subsequent tau PET accumulation. Log-transformed tau PET SUVR was used as the response and rates were summarized as annual per cent change. A temporal lobe tau PET meta-region of interest was used. In the cognitively unimpaired group, only higher baseline amyloid PET was a significant independent predictor of higher tau accumulation rates (P < 0.001). Higher rates of tau accumulation were associated with faster rates of cognitive decline in the cognitively unimpaired subgroup with abnormal amyloid PET (P = 0.03), but among the subgroup with normal amyloid PET. In the cognitively impaired group, younger age (P = 0.02), higher baseline amyloid PET (P = 0.05), APOE ε4 (P = 0.05), and better cognitive performance (P = 0.05) were significant independent predictors of higher tau accumulation rates. Among impaired individuals, faster cognitive decline was associated with faster rates of tau accumulation (P = 0.01). While we examined many possible predictor variables, our results indicate that screening of unimpaired individuals for potential inclusion in anti-tau trials may be straightforward because the only independent predictor of high tau rates was amyloidosis. In cognitively impaired individuals, imaging and clinical variables consistent with early onset Alzheimer’s disease phenotype were associated with higher rates of tau PET accumulation suggesting this may be a highly advantageous group in which to conduct proof-of-concept clinical trials that target tau-related mechanisms. The nature of the dementia phenotype (amnestic versus non-amnestic) did not affect this conclusion.
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DOI：
10.1016/j.jalz.2010.11.007
发表时间：
2011-01
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
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影响因子：
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影响因子：
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影响因子：
48
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影响因子：
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