缓解期老年期抑郁症患者的认知障碍与阿尔茨海默病相关的 CSF 生物标志物无关。
Cognitive impairment in remitted late-life depression is not associated with Alzheimer's disease-related CSF biomarkers.
机构信息
Laboratorio de Neurociencias LIM27, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil.
Laboratorio de Neurociencias LIM27, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brasil; UNESP- Universidade Estadual Paulista, Instituto de Biociências, Rio Claro, SP, Brasil.
出版信息
J Affect Disord. 2020 Jul 1;272:409-416. doi: 10.1016/j.jad.2020.03.166. Epub 2020 May 1.
BACKGROUND
Cognitive impairment is a common feature of late-life depression (LLD). Early studies using Alzheimer's disease (AD) biomarkers inferred a biological link between AD pathology and LLD, but recent findings have challenged this association. The aim of this investigation was to determine a panel of AD-related cerebrospinal fluid (CSF) biomarkers in a cross-section of elders with mild cognitive impairment (MCI) with and without LLD.
METHODS
Subjects comprised 102 older adults: 27 with 'pure' amnestic MCI (aMCI), 53 with major depression and cognitive impairment - encompassing 22 late-onset (LOD) and 31 early-onset depression (EOD), and 22 euthymic elders without cognitive impairment (controls). Participants underwent lumbar puncture for determination of CSF concentrations of Aβ, T-tau, and P-tau. Cut-off scores for suspected AD were: Aβ < 416p g/mL, P-tau > 36.1 pg/mL and Aβ/P-tau ratio < 9.53 (O. V. Forlenza et al. 2015). Statistical analyses consisted of analyses of variance (ANOVA), analyses of covariance (ANCOVA), Bonferroni post-hoc tests, and Pearson's chi-squared tests.
RESULTS
ANCOVA (age and schooling as covariates) displayed statistically significant results with respect to CSF biomarkers' profiles regardless of the socio-demographic divergencies previously identified by one-way ANOVA. Mean Aβ values (pg/mL) were: aMCI, 360.3 (p < 0.001); LOD, 486.6 (p < 0.001); EOD, 494.2 (p < 0.001); controls, 528.3 (p < 0.001); p< 0.05. Mean Aβ/P-tau ratio: aMCI, 7.9 (p < 0.001); LOD 14.2 (p < 0.001); EOD, 15.3 (p < 0.001); controls, 17.1 (p < 0.001); p < 0.05. Post-hoc tests indicated that patients with aMCI showed significant differences in biomarker profile compatible with AD signature.
LIMITATION
The main limitation is the relatively small sample.
CONCLUSION
Our findings suggest that, distinctively from aMCI, cognitive impairment in LLD is not associated with AD's CSF pathological signature.
背景
认知障碍是老年期抑郁症（LLD）的常见特征。早期使用阿尔茨海默病（AD）生物标志物的研究推断 AD 病理学与 LLD 之间存在生物学联系，但最近的发现对这种关联提出了挑战。本研究旨在确定一组 AD 相关的脑脊液（CSF）生物标志物，这些标志物存在于有和没有 LLD 的轻度认知障碍（MCI）老年人中。
方法
受试者包括 102 名老年人：27 名有“单纯”遗忘性 MCI（aMCI），53 名患有伴有认知障碍的重度抑郁症-包括 22 名晚发性（LOD）和 31 名早发性抑郁（EOD），以及 22 名无认知障碍的心境正常老年人（对照组）。参与者接受腰椎穿刺，以确定 CSF 中 Aβ、T-tau 和 P-tau 的浓度。疑似 AD 的截断值为：Aβ<416pg/ml，P-tau>36.1pg/ml 和 Aβ/P-tau 比值<9.53（O. V. Forlenza 等人，2015 年）。统计分析包括方差分析（ANOVA）、协方差分析（ANCOVA）、Bonferroni 事后检验和 Pearson's chi-squared 检验。
结果
无论先前通过单向方差分析确定的社会人口统计学差异如何，协方差分析（年龄和受教育程度为协变量）对 CSF 生物标志物谱显示出统计学上的显著结果。平均 Aβ 值（pg/ml）为：aMCI，360.3（p<0.001）；LOD，486.6（p<0.001）；EOD，494.2（p<0.001）；对照组，528.3（p<0.001）；p<0.05。平均 Aβ/P-tau 比值：aMCI，7.9（p<0.001）；LOD，14.2（p<0.001）；EOD，15.3（p<0.001）；对照组，17.1（p<0.001）；p<0.05。事后检验表明，aMCI 患者的生物标志物谱存在显著差异，与 AD 特征一致。
局限性
主要的限制是样本相对较小。
结论
我们的研究结果表明，与 aMCI 不同，LLD 中的认知障碍与 AD 的 CSF 病理特征无关。
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