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人体测量学和人口统计学特征会影响不同痴呆综合征患者和认知正常成年人的脑脊液生物标志物的解读。

Anthropometric and Demographic Features Affect the Interpretation of Cerebrospinal Fluid Biomarkers in Patients with Different Dementia Syndromes and Cognitively Healthy Adults.

机构信息

Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), Rua Botucatu 740, Vila Clementino, São Paulo, SP, CEP 04023-900, Brazil.

Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.

出版信息

Neuromolecular Med. 2024 Nov 1;26(1):43. doi: 10.1007/s12017-024-08810-4.

Abstract

Clinical distinction between dementia with Lewy bodies (DLB) and late-onset Alzheimer's disease (AD) is difficult, while several features might affect the analyses of biomarkers. This study aimed to verify associations of anthropometric and demographic features with cerebrospinal fluid biomarkers, their ratios, and restructured traditional regression formulas in patients with DLB and AD, as well as in cognitively healthy controls. Consecutive outpatients with DLB were paired with outpatients with AD according to sex, dementia stage, and cognitive status, and with controls according to sex and age to investigate associations of sex, age, dementia duration, total sleep time, body mass index, alcohol use, smoking, sanitation, and APOE-ε4 alleles on the measurement of cerebrospinal fluid α-synuclein, biomarker ratios, and restructured traditional regression formulas involving amyloid-β (Aβ,Aβ,Aβ), tau, and phospho-tau Thr. Overall, 81 participants were included with DLB (n = 27;11 APOE-ε4 +) or AD (n = 27;12 APOE-ε4 +), and controls (n = 27;4 APOE-ε4 +); two thirds were women. Cerebrospinal fluid evidence of amyloidosis and tauopathy was more prevalent among women with AD, while Aβ/Aβ could also discriminate men with DLB from men with AD. Restructured traditional regression formulas had higher diagnostic accuracy for women with AD. Aging, higher body mass index, and APOE-ε4 alleles were associated with amyloidosis in DLB, while only in AD were higher body mass index associated with lower tau pathology load, and more alcohol use associated with higher phospho-tau Thr/Aβ. These findings confirm the effects of anthropometric and demographic features on cerebrospinal fluid biomarkers, and also differences in aberrant amyloidosis and tauopathy between DLB and AD.

摘要

路易体痴呆(DLB)与晚发性阿尔茨海默病(AD)的临床鉴别较为困难,而一些特征可能会影响生物标志物的分析。本研究旨在验证性别、年龄、痴呆持续时间、总睡眠时间、体重指数、酒精使用、吸烟、卫生条件和 APOE-ε4 等位基因等人体测量和人口统计学特征与 DLB 和 AD 患者以及认知健康对照者的脑脊液生物标志物、其比值以及重构的传统回归公式之间的相关性。根据性别、痴呆阶段和认知状态,将连续就诊的 DLB 患者与 AD 患者配对,并根据性别和年龄与对照组进行配对,以调查性别、年龄、痴呆持续时间、总睡眠时间、体重指数、酒精使用、吸烟、卫生条件和 APOE-ε4 等位基因对脑脊液 α-突触核蛋白、生物标志物比值以及涉及淀粉样蛋白-β(Aβ、Aβ、Aβ)、tau 和磷酸化 tau Thr 的重构传统回归公式的影响。共有 81 名参与者被纳入研究,包括 DLB(n=27;11 个 APOE-ε4+)或 AD(n=27;12 个 APOE-ε4+)和对照组(n=27;4 个 APOE-ε4+);三分之二为女性。AD 女性患者的脑脊液淀粉样蛋白和 tau 病理证据更为常见,而 Aβ/Aβ 也可区分 DLB 男性与 AD 男性。重构的传统回归公式对 AD 女性的诊断准确性更高。在 DLB 中,老龄化、更高的体重指数和 APOE-ε4 等位基因与淀粉样蛋白有关,而仅在 AD 中,更高的体重指数与更低的 tau 病理负荷有关,更多的酒精使用与更高的磷酸化 tau Thr/Aβ 有关。这些发现证实了人体测量和人口统计学特征对脑脊液生物标志物的影响,以及 DLB 和 AD 之间异常淀粉样蛋白和 tau 病理的差异。

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