TY - JOUR T1 -阿尔茨海默病血液生物标志物在一个大型临床队列中预测痴呆风险的有效性和性能JF -神经学JO -神经学SP - e473 LP - e484 DO - 10.1212/WNL.0000000000201479半岛投注体育官网六世- 100 - 5盟Planche文森特盟——Bouteloup文森特AU - Pellegrin,伊莎贝尔盟-曼京,让非盟-杜布瓦,布鲁诺盟——Ousset Pierre-Jean盟——Pasquier佛罗伦萨AU -布兰科,克莱尔盟——Hanon Frederic AU - Paquet Olivier AU -本尼,卡里姆AU - Ceccaldi,马修AU - Annweiler,塞德里克AU - Krolak-Salmon,皮埃尔盟——Godefroy Olivier盟——Wallon大卫AU - Sauvee,马蒂尔德盟——Boutoleau-Bretonniere克莱尔AU - Bourdel-Marchasson,伊莎贝尔盟——JalenquesIsabelle AU - Chene, Genevieve AU - Dufouil, Carole AU -， Y1 - 2023/01/31 UR - http://n.n半岛投注体育官网eurology.org/content/100/5/e473.abstract N2 -背景和目的阿尔茨海默病(AD)的血液生物标志物一直被证明与CSF或PET生物标志物相关，并有效地将AD与其他神经退行性疾病区分开来。我们的目的是测试它们在临床实践中的效用，来自一个多中心的未选择的前瞻性队列，其中患者表现出大量的认知缺陷或抱怨。方法MEMENTO队列在法国26家记忆诊所招募了2323名主观认知抱怨(SCC)或轻度认知障碍(MCI)门诊患者。参与者在基线时进行神经心理学评估、核磁共振成像和血液采样。脑脊液取样和淀粉样PET是可选的。使用Simoa HD-X分析仪测量基线血a β42/40比值、总tau蛋白、p181-tau蛋白和神经丝轻链(NfL)。一个专家委员会在5年随访期间验证了痴呆事件病例。总的来说，2277个人至少有一个基线血液生物标志物可用(脑脊液子样本n = 357, PET子样本n = 649)，其中257人在随访期间被诊断为临床AD/混合性痴呆。除总tau蛋白外，所有血液生物标志物均与其脑脊液中的等效物轻度相关(r = 0.33 ~ 0.46, p < 0.0001) and were associated with amyloid-PET status (p < 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 [95% CI = 0.69; 0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aβ42/40 was less efficient than CSF Aβ42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 [95% CI = 0.69; 0.77]); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 [95% CI = 0.69; 0.97]) than in patients with CDR = 0.5 (c-index = 0.70 [95% CI = 0.66; 0.74]). A “clinical” reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 [95% CI = 0.86–0.91] and performance increased to 0.90 [95% CI = 0.88; 0.92] when adding blood p181-tau + Aβ42/40. A “research” reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 [95% CI = 0.89–0.93] increasing to 0.92 [95% CI = 0.90; 0.93] when adding blood p181-tau + Aβ42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances.Discussion In a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.Aβ=β-amyloid peptide; AD=Alzheimer disease; AUC=area under the curve; ApoE=apolipoprotein E; CDR=Clinical Dementia Rating; eGFR=estimated glomerular filtration rate; MCI=mild cognitive impairment; NfL=neurofilament light chain; ROC=receiver operating characteristic; SCC=subjective cognitive complaint; SUVR=standard uptake value ratio; TMT=Trail Making Test ER -