明尼苏达州神经学部门Ronald C. Petersen研究小组研究出淀粉样蛋白、Tau蛋白和神经退行性变生物标志物模型与无痴呆个体记忆衰退率的关系。2019年6月18日出版的《美国医学会杂志》发表了这项成果。

奥姆斯特德县以人群为基础的队列研究的认知老化明尼苏达州梅奥诊所,其中选取2015年4月16日到2017年11月1日之间包括480例未发病的梅奥临床研究受试者，进行临床评价和淀粉样蛋白正电子发射断层扫描(PET) (A),Tau蛋白 PET(T)和磁共振成像(MRI)皮质厚度(N) ,和至少1例临床评估持续到2018年11月12日。在这个纵向队列研究中,包括480名没有痴呆参与者,淀粉样正电子发射断层扫描,正电子发射断层扫描和磁共振成像大脑皮层厚度模型,包括临床和遗传变量导致一个小但对记忆衰退显著提高预测精度(R2, 0.31和0.26)。 在没有基线痴呆的老年人中，随访时间中位数为4.8年，预测模型包括淀粉样蛋白PET、Tau PET和MRI皮质厚度，与更容易获得临床和遗传变量的模型相比，预测记忆衰退的效果虽小，但在统计学上有显著改善。这种差异的临床重要性尚不确定。

据悉，一个国家老龄化和阿尔茨海默病协会工作组提出了一个阿尔茨海默病的研究框架，其中研究参与者的生物标志物分类标记为AT(N)，包括淀粉样蛋白、Tau蛋白和神经退行性生物标志物。

附：英文原文

Title: Associations of Amyloid, Tau, and Neurodegeneration Biomarker Profiles With Rates of Memory Decline Among Individuals Without Dementia

Author: Clifford R. Jack Jr, MD; Heather J. Wiste, BA; Terry M. Therneau, PhD; Stephen D. Weigand, MS; David S. Knopman, MD; Michelle M. Mielke, PhD; Val J. Lowe, MD; Prashanthi Vemuri, PhD; Mary M. Machulda, PhD; Christopher G. Schwarz, PhD; Jeffrey L. Gunter, PhD; Matthew L. Senjem, MS; Jonathan Graff-Radford, MD; David T. Jones, MD; Rosebud O. Roberts, MB, ChB; Walter A. Rocca, MD; Ronald C. Petersen, MD, PhD

Issue&Volume: Vol 321, No. 23,2019

Abstract:Importance A National Institute on Aging and Alzheimer’s Association workgroup proposed a research framework for Alzheimer disease in which biomarker classification of research participants is labeled AT(N) for amyloid, tau, and neurodegeneration biomarkers.

Objective To determine the associations between AT(N) biomarker profiles and memory decline in a population-based cohort of individuals without dementia age 60 years or older, and to determine whether biomarkers provide incremental prognostic value beyond more readily available clinical and genetic information.

Design, Setting, and Participants Population-based cohort study of cognitive aging in Olmsted County, Minnesota, that included 480 nondemented Mayo Clinic Study of Aging participants who had a clinical evaluation and amyloid positron emission tomography (PET) (A), tau PET (T), and magnetic resonance imaging (MRI) cortical thickness (N) measures between April 16, 2015, and November 1, 2017, and at least 1 clinical evaluation follow-up by November 12, 2018.

Exposures Age, sex, education, cardiovascular and metabolic conditions score, APOE genotype, and AT(N) biomarker profiles. Each of A, T, or (N) can be abnormal (+) or normal (−), resulting in 8 AT(N) profiles.

Main Outcomes and Measures Primary outcome was a composite memory score measured longitudinally at 15-month intervals. Analyses measured the associations between predictor variables and the memory score, and whether AT(N) biomarker profiles significantly improved prediction of memory z score rates of change beyond a model with clinical and genetic variables only.

Results Participants were followed up for a median of 4.8 years (interquartile range [IQR], 3.8-5.1) and 44% were women (211/480). Median (IQR) ages ranged from 67 years (65-73) in the A−T−(N)− group to 83 years (76-87) in the A+T+(N)+ group. Of the participants, 92% (441/480) were cognitively unimpaired but the A+T+(N)+ group had the largest proportion of mild cognitive impairment (30%). AT(N) biomarkers improved the prediction of memory performance over a clinical model from an R2 of 0.26 to 0.31 (P < .001). Memory declined fastest in the A+T+(N)+, A+T+(N)−, and A+T−(N)+ groups compared with the other 5 AT(N) groups (P = .002). Estimated rates of decline in the 3 fastest declining groups were −0.13 (95% CI, −0.17 to −0.09), −0.10 (95% CI, −0.16 to −0.05), and −0.10 (95% CI, −0.13 to −0.06) z score units per year, respectively, for an 85-year-old APOE ε4 noncarrier.

Conclusions and Relevance Among older persons without baseline dementia followed for a median of 4.8 years, a prediction model that included amyloid PET, tau PET, and MRI cortical thickness resulted in a small but statistically significant improvement in predicting memory decline over a model with more readily available clinical and genetic variables. The clinical importance of this difference is uncertain.

DOI: 10.1001/jama.2019.7437

Source: https://jamanetwork.com/journals/jama/article-abstract/2735818