Wei Hui, Masurkar Arjun V, Razavian Narges
Manning College of Information and Computer Sciences, University of Massachusetts Amherst, Amherst, MA, United States.
Department of Population Health, NYU Grossman School of Medicine, New York, NY, United States.
Front Aging Neurosci. 2023 Mar 21;15:1149036. doi: 10.3389/fnagi.2023.1149036. eCollection 2023.
Alzheimer's disease (AD) and Lewy body disease (LBD) are the two most common neurodegenerative dementias and can occur in combination (AD+LBD). Due to overlapping biomarkers and symptoms, clinical differentiation of these subtypes could be difficult. However, it is unclear how the magnitude of diagnostic uncertainty varies across dementia spectra and demographic variables. We aimed to compare clinical diagnosis and post-mortem autopsy-confirmed pathological results to assess the clinical subtype diagnosis quality across these factors.
We studied data of 1,920 participants recorded by the National Alzheimer's Coordinating Center from 2005 to 2019. Selection criteria included autopsy-based neuropathological assessments for AD and LBD, and the initial visit with Clinical Dementia Rating (CDR) stage of normal, mild cognitive impairment, or mild dementia. Longitudinally, we analyzed the first visit at each subsequent CDR stage. This analysis included positive predictive values, specificity, sensitivity and false negative rates of clinical diagnosis, as well as disparities by sex, race, age, and education. If autopsy-confirmed AD and/or LBD was missed in the clinic, the alternative clinical diagnosis was analyzed.
In our findings, clinical diagnosis of AD+LBD had poor sensitivities. Over 61% of participants with autopsy-confirmed AD+LBD were diagnosed clinically as AD. Clinical diagnosis of AD had a low sensitivity at the early dementia stage and low specificities at all stages. Among participants diagnosed as AD in the clinic, over 32% had concurrent LBD neuropathology at autopsy. Among participants diagnosed as LBD, 32% to 54% revealed concurrent autopsy-confirmed AD pathology. When three subtypes were missed by clinicians, "No cognitive impairment" and "primary progressive aphasia or behavioral variant frontotemporal dementia" were the leading primary etiologic clinical diagnoses. With increasing dementia stages, the clinical diagnosis accuracy of black participants became significantly worse than other races, and diagnosis quality significantly improved for males but not females.
These findings demonstrate that clinical diagnosis of AD, LBD, and AD+LBD are inaccurate and suffer from significant disparities on race and sex. They provide important implications for clinical management, anticipatory guidance, trial enrollment and applicability of potential therapies for AD, and promote research into better biomarker-based assessment of LBD pathology.
阿尔茨海默病（AD）和路易体病（LBD）是两种最常见的神经退行性痴呆，且可能合并出现（AD+LBD）。由于生物标志物和症状存在重叠，这些亚型的临床鉴别可能具有挑战性。然而，目前尚不清楚诊断不确定性的程度在不同痴呆谱系和人口统计学变量之间如何变化。我们旨在比较临床诊断与尸检确诊的病理结果，以评估这些因素对临床亚型诊断质量的影响。
我们研究了美国国立阿尔茨海默病协调中心在2005年至2019年期间记录的1920名参与者的数据。入选标准包括基于尸检的AD和LBD神经病理学评估，以及初次就诊时临床痴呆评定量表（CDR）处于正常、轻度认知障碍或轻度痴呆阶段。纵向来看，我们分析了每个后续CDR阶段的初次就诊情况。该分析包括临床诊断的阳性预测值、特异性、敏感性和假阴性率，以及按性别、种族、年龄和教育程度划分的差异。如果临床漏诊了经尸检确诊的AD和/或LBD，则分析替代临床诊断。
在我们的研究结果中，AD+LBD的临床诊断敏感性较差。超过61%经尸检确诊为AD+LBD的参与者在临床上被诊断为AD。AD的临床诊断在早期痴呆阶段敏感性较低，在所有阶段特异性均较低。在临床上被诊断为AD的参与者中，超过32%在尸检时伴有LBD神经病理学改变。在被诊断为LBD的参与者中，32%至54%在尸检时显示同时存在经确诊的AD病理改变。当临床医生漏诊三种亚型时，“无认知障碍”和“原发性进行性失语或行为变异型额颞叶痴呆”是主要的原发性病因临床诊断。随着痴呆阶段的增加，黑人参与者的临床诊断准确性明显低于其他种族，男性的诊断质量显著提高，而女性则不然。
这些研究结果表明，AD、LBD和AD+LBD的临床诊断不准确，且在种族和性别方面存在显著差异。它们对临床管理、预期指导、试验入组以及AD潜在治疗方法的适用性具有重要意义，并促进了对基于更好生物标志物的LBD病理学评估的研究。
