Sex-specific associations with cerebrospinal fluid biomarkers in dementia with Lewy bodies
Sex-specific associations with cerebrospinal fluid biomarkers in dementia with Lewy bodies
复制标题
路易体痴呆中脑脊液生物标志物的性别特异性关联
DOI：
10.1186/s13195-020-00610-9
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
W. V. D. Flier
中科院分区：
文献类型：
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作者：
M. Beek;R. B. Mofrad;I. V. Steenoven;H. Vanderstichele;Ph. Scheltens;C. Teunissen;A. Lemstra;W. V. D. Flier
背景路易体痴呆（DLB）在男性中比女性更普遍。此外，尸检研究发现潜在病理学存在性别差异。目前尚不清楚这些差异是否也存在于死前体内生物标志物中，以及性别差异是否转化为临床表现的变异性。本研究的目的是评估脑脊液（CSF）生物标志物浓度的性别差异（即，α-突触核蛋白（α-syn）、淀粉样蛋白β1-42（Aβ42）、总tau（Tau）、磷酸化tau（pTau））和DLB的临床特征。方法我们纳入了223例来自阿姆斯特丹痴呆队列的DLB患者，其中39例为女性（17%，年龄70 ± 6，MMSE 21 ± 6），184例为男性（83%，年龄68 ± 7，MMSE 23 ± 4）。CSF生物标志物浓度的性别差异（即，使用年龄校正的一般线性模型（GLM）评价α-syn、Aβ42、Tau和pTau）。此外，我们分析了核心临床特征的性别差异（即，幻视、帕金森综合征、认知波动和REM睡眠行为障碍（RBD）以及使用年龄和教育调整的GLM的认知测试分数。结果女性CSF α-syn水平（F 1429 ± 164 vs M 1831 ± 60，p = 0.02）和CSF Aβ42水平（F 712 ± 39 vs M 821 ± 18，p = 0.01）低于男性。（p）Tau浓度无性别差异（p > 0.05）。临床上，女性年龄较大，主诉持续时间较短（F2 ± 1 vs M4 ± 3，p < 0.001），幻觉发生频率较高（58% vs 38%，p = 0.02），MMSE和流畅性任务评分较低（MMSE，p = 0.02;动物流畅性，p = 0.006）。男性和女性在波动、RBD、帕金森症或其他认知测试方面没有差异。结论女性的Aβ42和α-syn水平低于男性，且主诉持续时间较短。此外，在诊断时，女性的认知测试分数较低，幻觉更频繁。根据我们的研究结果，可以假设与男性相比，女性在DLB中具有更具侵略性的疾病过程。未来的研究应调查女性和男性DLB是否可能受益于性别特异性治疗策略。
Background Dementia with Lewy bodies (DLB) is more prevalent in men than in women. In addition, post-mortem studies found sex differences in underlying pathology. It remains unclear whether these differences are also present antemortem in in vivo biomarkers, and whether sex differences translate to variability in clinical manifestation. The objective of this study was to evaluate sex differences in cerebrospinal fluid (CSF) biomarker concentrations (i.e., alpha-synuclein (α-syn), amyloid β1-42 (Aβ42), total tau (Tau), phosphorylated tau at threonine 181 (pTau)) and clinical characteristics in DLB. Methods We included 223 DLB patients from the Amsterdam Dementia Cohort, of which 39 were women (17%, age 70 ± 6, MMSE 21 ± 6) and 184 men (83%, age 68 ± 7, MMSE 23 ± 4). Sex differences in CSF biomarker concentrations (i.e., α-syn, Aβ42, Tau, and pTau) were evaluated using age-corrected general linear models (GLM). In addition, we analyzed sex differences in core clinical features (i.e., visual hallucinations, parkinsonism, cognitive fluctuations, and REM sleep behavior disorder (RBD) and cognitive test scores using age- and education-adjusted GLM. Results Women had lower CSF α-syn levels (F 1429 ± 164 vs M 1831 ± 60, p = 0.02) and CSF Aβ42 levels (F 712 ± 39 vs M 821 ± 18, p = 0.01) compared to men. There were no sex differences for (p) Tau concentrations ( p > 0.05). Clinically, women were older, had a shorter duration of complaints (F 2 ± 1 vs M 4 ± 3, p < 0.001), more frequent hallucinations (58% vs 38%, p = 0.02), and scored lower on MMSE and a fluency task (MMSE, p = 0.02; animal fluency, p = 0.006). Men and women did not differ on fluctuations, RBD, parkinsonism, or other cognitive tests. Conclusions Women had lower Aβ42 and α-syn levels than men, alongside a shorter duration of complaints. Moreover, at the time of diagnosis, women had lower cognitive test scores and more frequent hallucinations. Based on our findings, one could hypothesize that women have a more aggressive disease course in DLB compared to men. Future research should investigate whether women and men with DLB might benefit from sex-specific treatment strategies.
路易体疾病范围内的脑脊液阿尔茨海默氏病生物标志物：来自大型多中心队列的结果。
DOI：
10.3233/jad-160322
发表时间：
2016
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
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作者：
vanSteenoven,Inger;Aarsland,Dag;Weintraub,Daniel;Londos,Elisabet;Blanc,Frédéric;vanderFlier,WiesjeM;Teunissen,CharlotteE;Mollenhauer,Brit;Fladby,Tormod;Kramberger,MilicaG;Bonanni,Laura;Lemstra,AfinaW;EuropeanDLBconsortium
通讯作者：
EuropeanDLBconsortium
影响因子：
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作者：
Barnes, LL;Wilson, RS;Bennett, DA
通讯作者：
Bennett, DA