From the Clinical Memory Research Unit, Department of Clinical Sciences (N.M.-C., A.L., S.J., S.P., E.S., O.S., R.S., O.H.), and Wallenberg Centre for Molecular Medicine (N.M.-C.), Lund University, Malmö; and Department of Neurology (N.M.-C., S.P., R.S.) and Memory Clinic (E.S., O.H.), Skåne University Hospital, Lund, Sweden.
Neurology. 2020 May 26;94(21):e2233-e2244. doi: 10.1212/WNL.0000000000009485. Epub 2020 May 12.
To compare different β-amyloid (Aβ), tau, and neurodegeneration (AT[N]) variants within the Swedish BioFINDER studies.
A total of 490 participants were classified into AT(N) groups. These include 53 cognitively unimpaired (CU) and 48 cognitively impaired (CI) participants (14 mild cognitive impairment [MCI] and 34 Alzheimer disease [AD] dementia) from BioFINDER-1 and 389 participants from BioFINDER-2 (245 CU and 144 CI [138 MCI and 6 AD dementia]). Biomarkers for A were CSF Aβ and amyloid-PET ([F]flutemetamol); for T, CSF phosphorylated tau (p-tau) and tau PET ([F]flortaucipir); and for (N), hippocampal volume, temporal cortical thickness, and CSF neurofilament light (NfL). Binarization of biomarkers was achieved using cutoffs defined in other cohorts. The relationship between different AT(N) combinations and cognitive trajectories (longitudinal Mini-Mental State Examination scores) was examined using linear mixed modeling and coefficient of variation.
Among CU participants, A-T-(N)- or A+T-(N)- variants were most common. However, more T+ cases were seen using p-tau than tau PET. Among CI participants, A+T+(N)+ was more common; however, more (N)+ cases were seen for MRI measures relative to CSF NfL. Tau PET best predicted longitudinal cognitive decline in CI and p-tau in CU participants. Among CI participants, continuous T (especially tau PET) and (N) measures improved the prediction of cognitive decline compared to binary measures.
Our findings show that different AT(N) variants are not interchangeable, and that optimal variants differ by clinical stage. In some cases, dichotomizing biomarkers may result in loss of important prognostic information.
比较瑞典 BioFINDER 研究中的不同β-淀粉样蛋白（Aβ）、tau 和神经退行性变（AT[N]）变异体。
共有 490 名参与者被分为 AT[N]组。这些包括来自 BioFINDER-1 的 53 名认知正常（CU）和 48 名认知受损（CI）参与者（14 名轻度认知障碍 [MCI]和 34 名阿尔茨海默病 [AD]痴呆）以及来自 BioFINDER-2 的 389 名参与者（245 名 CU 和 144 名 CI [138 名 MCI 和 6 名 AD 痴呆]）。A 的生物标志物为 CSF Aβ 和淀粉样蛋白-PET ([F]flutemetamol)；T 的生物标志物为 CSF 磷酸化 tau（p-tau）和 tau PET ([F]flortaucipir)；(N) 的生物标志物为海马体积、颞叶皮质厚度和 CSF 神经丝轻链（NfL）。使用其他队列中定义的截止值对生物标志物进行二值化。使用线性混合模型和变异系数检查不同 AT[N]组合与认知轨迹（纵向 Mini-Mental State Examination 评分）之间的关系。
在 CU 参与者中，A-T-(N)-或 A+T-(N)-变异体最常见。然而，与 tau PET 相比，p-tau 检测到更多的 T+病例。在 CI 参与者中，A+T+(N)+更为常见；然而，相对于 CSF NfL，MRI 测量结果显示更多的（N）+病例。tau PET 可最好地预测 CI 参与者的纵向认知下降，而 p-tau 可预测 CU 参与者的纵向认知下降。在 CI 参与者中，与二进制测量相比，连续 T（特别是 tau PET）和（N）测量可改善认知下降的预测。
我们的研究结果表明，不同的 AT[N]变异体不可互换，并且最佳变异体因临床阶段而异。在某些情况下，将生物标志物二值化可能会导致重要预后信息的丢失。
