Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals.
Tau-PET and in vivo Braak-staging as prognostic markers of future cognitive decline in cognitively normal to demented individuals.
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DOI：
10.1186/s13195-021-00880-x
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发表时间：
2021-08-12
期刊：
影响因子：
--
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
中科院分区：
文献类型：
--
作者：
Biel D;Brendel M;Rubinski A;Buerger K;Janowitz D;Dichgans M;Franzmeier N;Alzheimer’s Disease Neuroimaging Initiative (ADNI)
系统地研究 tau-PET 和 Braak 分期作为有或没有认知障碍的老年人未来认知能力下降的预后标志物的临床效用。在这项纵向研究中，我们纳入了 396 名认知正常的痴呆受试者，进行了 18F-Florbetapir/18F-Florbetaben-amyloid-PET、18F-Flortaucipir-tau-PET 和 2 年认知随访。通过线性混合模型计算全局认知（即 MMSE、ADAS13）和情景记忆的年度变化率。我们确定了整体淀粉样蛋白-PET (Centiloid) 加上整体和 Braak 阶段特异性 tau-PET SUVR，这些 SUVR 在预先设定的截止点处分层为阳性 (+)/阴性 (−)，将受试者分类为 Braak0/BraakI+/BraakI–IV+/BraakI–VI+/Braakatropic+。在引导线性回归中，我们评估了全局 tau-PET SUVR 与 Centiloid 对随后认知能力下降的预测准确性。为了测试独立的 tau 蛋白与淀粉样蛋白的效应，进一步对照相反的 PET 示踪剂进行分析。使用ANCOVA，我们测试了更高级的布拉克阶段是否预示着未来认知能力的加速衰退。所有模型均针对年龄、性别、教育程度、诊断和基线认知进行控制。最后，我们确定了 Braak 阶段特定的轻度认知障碍 (MCI) 或痴呆的转化风险。在所有认知测试（Cohen’s d ~ 2，所有测试 p < 0.001）和诊断组中，基线全局 tau-PET SUVR 比 Centiloid 解释了未来认知衰退的更多方差（部分 R2）。在控制 Centiloid 时，tau-PET 与认知能力下降之间的关联保持一致，而在控制 tau-PET 时，淀粉样蛋白-PET 与认知能力下降之间的关联并不显着。更晚期的 Braak 阶段与未来逐渐恶化的认知能力下降相关，与 Centiloid 或诊断组无关 (p<0.001)，并且转化为 MCI/痴呆的风险升高。 Tau-PET 和 Braak 分期是未来认知能力下降的高度预测标志物，并且可能是临床环境中预测患者特异性进展风险的单一模式估计。在线版本包含可在 10.1186/s13195-021-00880-x 获取的补充材料。
To systematically examine the clinical utility of tau-PET and Braak-staging as prognostic markers of future cognitive decline in older adults with and without cognitive impairment. In this longitudinal study, we included 396 cognitively normal to dementia subjects with 18F-Florbetapir/18F-Florbetaben-amyloid-PET, 18F-Flortaucipir-tau-PET and ~ 2-year cognitive follow-up. Annual change rates in global cognition (i.e., MMSE, ADAS13) and episodic memory were calculated via linear-mixed models. We determined global amyloid-PET (Centiloid) plus global and Braak-stage-specific tau-PET SUVRs, which were stratified as positive(+)/negative(−) at pre-established cut-offs, classifying subjects as Braak0/BraakI+/BraakI–IV+/BraakI–VI+/Braakatypical+. In bootstrapped linear regression, we assessed the predictive accuracy of global tau-PET SUVRs vs. Centiloid on subsequent cognitive decline. To test for independent tau vs. amyloid effects, analyses were further controlled for the contrary PET-tracer. Using ANCOVAs, we tested whether more advanced Braak-stage predicted accelerated future cognitive decline. All models were controlled for age, sex, education, diagnosis, and baseline cognition. Lastly, we determined Braak-stage-specific conversion risk to mild cognitive impairment (MCI) or dementia. Baseline global tau-PET SUVRs explained more variance (partial R2) in future cognitive decline than Centiloid across all cognitive tests (Cohen’s d ~ 2, all tests p < 0.001) and diagnostic groups. Associations between tau-PET and cognitive decline remained consistent when controlling for Centiloid, while associations between amyloid-PET and cognitive decline were non-significant when controlling for tau-PET. More advanced Braak-stage was associated with gradually worsening future cognitive decline, independent of Centiloid or diagnostic group (p < 0.001), and elevated conversion risk to MCI/dementia. Tau-PET and Braak-staging are highly predictive markers of future cognitive decline and may be promising single-modality estimates for prognostication of patient-specific progression risk in clinical settings. The online version contains supplementary material available at 10.1186/s13195-021-00880-x.
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DOI：
10.1093/brain/awaa248
发表时间：
2020-10-01
期刊：
Brain : a journal of neurology
影响因子：
--
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
通讯作者：
Petersen RC
影响因子：
3.2
作者：
Crane, Paul K.;Carle, Adam;Gibbons, Laura E.;Insel, Philip;Mackin, R. Scott;Gross, Alden;Jones, Richard N.;Mukherjee, Shubhabrata;Curtis, S. McKay;Harvey, Danielle;Weiner, Michael;Mungas, Dan
通讯作者：
Mungas, Dan
影响因子：
15.1
作者：
Franzmeier N;Suárez-Calvet M;Frontzkowski L;Moore A;Hohman TJ;Morenas-Rodriguez E;Nuscher B;Shaw L;Trojanowski JQ;Dichgans M;Kleinberger G;Haass C;Ewers M;Alzheimer’s Disease Neuroimaging Initiative (ADNI)
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative (ADNI)
影响因子：
11
作者：
Franzmeier, Nicolai;Ren, Jinyi;Ewers, Michael
通讯作者：
Ewers, Michael
影响因子：
16.6
作者：
Franzmeier, Nicolai;Rubinski, Anna;Simpson, Donna M.
通讯作者：
Simpson, Donna M.