Jali Vidishaa, Zhang Qinglin, Chong Joyce Ruifen, Wong Damon, Tan Bingyao, Garhöfer Gerhard, Hilal Saima, Lai Mitchell K P, Schmetterer Leopold, Chen Christopher Li-Hsian, Chua Jacqueline
Department of Pharmacology, Memory Aging and Cognition Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore.
Department of Neurosurgery, Tsinghua University Yuquan Hospital, Beijing 100040, China.
Brain Commun. 2024 Dec 27;7(1):fcae472. doi: 10.1093/braincomms/fcae472. eCollection 2025.
Accurate and early diagnosis of Alzheimer's disease and vascular dementia is crucial for enabling timely interventions and improving patient outcomes. This study evaluates the diagnostic performance of plasma biomarkers (neurofilament light chain and phosphorylated tau181) and retinal biomarkers (retinal nerve fibre layer and ganglion cell-inner plexiform layer), individually and in combination, in differentiating moderate cognitive impairment and dementia from mild cognitive impairment and no cognitive impairment. A cross-sectional study was conducted involving 509 participants, aged 50 and older, recruited from a memory clinic. The participants were categorized as normal ( = 100), mild cognitive impairment ( = 144), moderate cognitive impairment ( = 90) or dementia ( = 175) based on detailed clinical assessments, neuropsychological testing and MRI scans. The thickness of the ganglion cell-inner plexiform layer ( < 0.001) and retinal nerve fibre layer ( = 0.030) decreased progressively from normal cognition to cognitive impairment and dementia. The thickest layers were observed in individuals with no cognitive impairment (mean ± standard deviation: ganglion cell-inner plexiform layer: 76 ± 11 µm, retinal nerve fibre layer: 92 ± 10 µm), while the thinnest layers were found in individuals with dementia (ganglion cell-inner plexiform layer: 72 ± 14 µm, retinal nerve fibre layer: 89 ± 12 µm). Plasma biomarker levels increased progressively from normal cognition to cognitive impairment and dementia ( < 0.001). Levels were lowest in individuals with no cognitive impairment [median (interquartile range): neurofilament light chain: 15 (9) pg/mL, phosphorylated tau181: 1.85 (1.00) pg/mL] and highest in those with dementia [neurofilament light chain: 34 (27) pg/mL, phosphorylated tau181: 3.24 (2.81) pg/mL]. After adjusting for retinal scan signal strength, neurofilament light chain showed a stronger negative association with retinal nerve fibre layer thickness [standardized beta estimate () = -0.184] and ganglion cell-inner plexiform layer thickness ( = -0.139) compared to phosphorylated tau181, which exhibited weaker associations with ganglion cell-inner plexiform layer ( = -0.091) and retinal nerve fibre layer ( = -0.059). While retinal parameters provided modest discriminatory ability (AUC = 0.60), plasma biomarkers demonstrated superior diagnostic performance (AUC = 0.76). Notably, neurofilament light chain had a stronger association with retinal thinning than phosphorylated tau181 and offered superior diagnostic value for identifying moderate cognitive decline. These findings underscore the potential of plasma biomarkers, particularly neurofilament light chain, for the early detection of dementia.
准确且早期诊断阿尔茨海默病和血管性痴呆对于及时进行干预并改善患者预后至关重要。本研究评估了血浆生物标志物（神经丝轻链和磷酸化tau181）以及视网膜生物标志物（视网膜神经纤维层和神经节细胞 - 内丛状层）单独及联合使用时，在区分中度认知障碍和痴呆与轻度认知障碍及无认知障碍方面的诊断性能。进行了一项横断面研究，纳入了从记忆诊所招募的509名年龄在50岁及以上的参与者。根据详细的临床评估、神经心理学测试和MRI扫描，将参与者分为正常组（ = 100）、轻度认知障碍组（ = 144）、中度认知障碍组（ = 90）或痴呆组（ = 175）。神经节细胞 - 内丛状层（ < 0.001）和视网膜神经纤维层（ = 0.030）的厚度从正常认知到认知障碍和痴呆逐渐降低。在无认知障碍的个体中观察到最厚的层（平均值±标准差：神经节细胞 - 内丛状层：76±11 µm，视网膜神经纤维层：92±10 µm），而在痴呆个体中发现最薄的层（神经节细胞 - 内丛状层：72±14 µm，视网膜神经纤维层：89±12 µm）。血浆生物标志物水平从正常认知到认知障碍和痴呆逐渐升高（ < 0.001）。在无认知障碍的个体中水平最低[中位数（四分位间距）：神经丝轻链：15（9）pg/mL，磷酸化tau181：1.85（1.00）pg/mL]，在痴呆个体中最高[神经丝轻链：34（27）pg/mL，磷酸化tau181：3.24（2.81）pg/mL]。在调整视网膜扫描信号强度后，与磷酸化tau181相比，神经丝轻链与视网膜神经纤维层厚度[标准化β估计值（） = -0.184]和神经节细胞 - 内丛状层厚度（ = -0.139）的负相关性更强，而磷酸化tau181与神经节细胞 - 内丛状层（ = -0.091）和视网膜神经纤维层（ = -0.059）的相关性较弱。虽然视网膜参数具有一定的鉴别能力（AUC = 0.60），但血浆生物标志物表现出更优的诊断性能（AUC = 0.76）。值得注意的是，神经丝轻链与视网膜变薄的相关性比磷酸化tau181更强，并且在识别中度认知衰退方面具有更高的诊断价值。这些发现强调了血浆生物标志物，尤其是神经丝轻链，在痴呆早期检测中的潜力。
