背景:脑脊液(CSF)-淀粉样β(Aβ)42,CSF-Aβ40,CSF-Aβ38,CSF可溶性淀粉样前体蛋白α和β的异常,CSF-总-tau,CSF-磷酸化-tau,CSF-神经丝光蛋白(NF-L),CSF-神经颗粒素,血浆Aβ42,血浆Aβ40,血浆总tau,血浆-NF-L和,情感发作期间的血清S100B可能反映了可能影响双相情感障碍(BD)患者认知功能的大脑变化。该研究旨在调查这些指示阿尔茨海默病的生物标志物与反映神经变性的生物标志物之间的关联,以及它们对BD患者和健康对照者(HC)认知功能的影响。主要假设是基于来自BD和HC中的T0和T3的数据,GL和VL将随着CSF-Aβ42水平的增加而增加。
方法:在前瞻性中,在基线时(T0)和1年后(T3)正常时,通过临床评估和神经心理学测试对BD(N=85)和HC(N=44)患者的正常心理进行了评估.每周记录患者的情感状态,亚阈值水平,严重的抑郁症,或(低度)躁狂症。如果在随访期间发生了发作,还评估了患者的发作后精神状态.认知表现被测量为包括语言学习和记忆(VL)在内的四个认知领域的全局认知得分(GL)。
结果:在线性混合模型中,对于每增加1pg/ml的CSF-Aβ42,GL估计增加0.001(97.5%,CI0.00043-0.0018,调整后p=0.0005),而VL增加0.00089(97.5%,CI0.00015-0.0018,调整后-p=0.045)在BD和HC中的联合。协会很弱,然而,与HC相比,BD患者更强。其他生物标志物之间的关联,包括CSF-神经颗粒素,认知领域整体较弱,在多次测试调整后,没有一个仍然显著。
结论:样本量适中。仅从61名BD患者和38名HC患者获得了有关CSF-AB-42和认知测试得分的完整数据集。
结论:CSF-Aβ42可能与BD和HC患者的认知功能障碍有关。BD中的关联似乎更强,但置信区间重叠。因此,这种关联是普遍现象还是由BD驱动仍然不确定。
BACKGROUND: Abnormalities in cerebrospinal fluid (CSF)-
amyloid-beta (Aβ)42, CSF-Aβ40, CSF-Aβ38, CSF-soluble
amyloid precursor proteins α and β, CSF-total-tau, CSF-phosphorylated-tau, CSF-neurofilament light protein (NF-L), CSF-neurogranin, plasma-Aβ42, plasma-Aβ40, plasma-total-tau, plasma-NF-L and, serum-S100B during affective episodes may reflect brain changes that could impact cognitive function in patients with bipolar disorder (BD). The study aimed to investigate the association between these biomarkers indicative of Alzheimer\'s disease and those reflecting neurodegeneration alongside their impact on cognitive function in patients with BD and healthy control individuals (HC). The primary hypothesis was that GL and VL would increase with increasing levels of CSF-Aβ42 based on data from T0 and T3 in BD and HC jointly.
METHODS: In a prospective, longitudinal
case-control study euthymic patients with BD (N = 85) and HC (N = 44) were evaluated with clinical assessment and neuropsychological testing at baseline (T0) and during euthymia after a year (T3). Patients\' affective states were recorded weekly as euthymic, subthreshold level, major depression, or (hypo)mania. If an episode occurred during follow-up, the patient was also assessed in post-episode euthymia. Cognitive performance was measured as a global cognitive score (GL) for four cognitive domains including verbal learning and memory (VL).
RESULTS: Estimated in a linear mixed model GL increased with 0.001 for each increase of 1 pg/ml of CSF-Aβ42 (97.5%, CI 0.00043-0.0018, adjusted-p = 0.0005) while VL increased by 0.00089 (97.5%, CI 0.00015-0.0018, adjusted-p = 0.045) in BD and HC jointly. The association was weak, however stronger in patients with BD compared to HC. Associations between other biomarkers including CSF-neurogranin, and cognitive domains were overall weak, and none remained significant after adjustment for multiple testing.
CONCLUSIONS: Modest sample size. A complete data set regarding both CSF-AB-42 and cognitive test scores was obtained from merely 61 patients with BD and 38 HC individuals.
CONCLUSIONS: CSF-Aβ42 may be associated with cognitive dysfunction in patients with BD and HC individuals. The association appeared to be stronger in BD but with overlapping confidence intervals. Hence it remains uncertain whether the association is a general phenomenon or driven by BD.