%0期刊文章%文森特·普朗什%文森特·布特鲁%伊莎贝尔·佩莱格林%让·弗朗索瓦%布鲁诺·杜布瓦%皮埃尔-让·乌塞特%弗洛伦斯·帕斯卡%弗雷德里克·布兰克%克莱尔·帕奎特%奥利维·哈诺%卡里姆·本尼%马蒂厄·塞卡尔迪% Cédric安韦勒%皮埃尔·克劳克-萨尔蒙%奥利维·戈德弗罗伊%大卫·瓦隆%玛蒂尔德·索维%克莱尔Boutoleau-Bretonnière %伊莎贝尔·布尔-马尔查森%伊莎贝尔·贾伦奎斯%吉纳维芙·陈%卡罗尔·杜富尔%A和记忆物研究在一项大型临床队列研究中，阿尔茨海默病血液生物标志物预测痴呆风险的有效性和性能%D 2023 %R 10.1212/WNL。背景和目的阿尔茨海默病(AD)的血液生物首页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外的所有血液生物标志物与其在脑脊液中的等效性轻度相关(r = 0.33至0.46,p < 0.0001)，并与淀粉样蛋白- pet状态相关(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 %U //www.ez-admanager.com/content/neurology/100/5/e473.full.pdf

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