心脑轴血管疾病患者的阿尔茨海默病和认知能力下降。
Alzheimer's Disease and Cognitive Decline in Patients with Cardiovascular Diseases Along the Heart-Brain Axis.
机构信息
Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam University Medical Center (Amsterdam UMC), Amsterdam, The Netherlands.
Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam, The Netherlands.
出版信息
J Alzheimers Dis. 2024;98(3):987-1000. doi: 10.3233/JAD-231096.
BACKGROUND
We hypothesize that Alzheimer's disease (AD)-related pathology may accelerate cognitive decline in patients with cardiovascular diseases.
OBJECTIVE
To investigate the association between blood-based biomarkers of AD, astrocyte activation, and neurodegeneration and cognitive decline.
METHODS
From the multi-center Heart-Brain study, we included 412 patients with heart failure, carotid occlusive disease or vascular cognitive impairment (age:68.6±9.0) and 128 reference participants (65.7±7.5). Baseline amyloid-β42/40 (Aβ42/40), phosphorylated-tau181 (pTau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were determined using SiMoA (Quanterix). Memory, attention, language, and executive functioning were evaluated (follow-up:2.1±0.3 years). We applied linear mixed models with terms for biomarker, time and biomarker*time interactions, adjusted for age, sex, education, and site, to assess associations between biomarkers and cognitive decline.
RESULTS
Among patients, Aβ42/40 was not associated with cognitive performance at baseline. However, lower Aβ42/40 was associated with steeper decline in global cognition (β±SE:0.04±0.02). Higher pTau181 was associated with worse baseline performance on global cognition (-0.14±0.04) and memory (-0.31±0.09) and with steeper decline in global cognition (-0.07±0.02), memory (-0.09±0.04), attention (-0.05±0.02), and language (-0.10±0.03). Higher GFAP was associated with worse baseline performance on global cognition (-0.22±0.05), memory (-0.43±0.10), attention (-0.14±0.06), language (-0.15±0.05), and executive functioning (-0.15±0.05) and steeper decline in global cognition (-0.05±0.01). Higher NfL was associated with worse baseline performance on global cognition (-0.16±0.04), memory (-0.28±0.09), attention (-0.20±0.06), and executive functioning (-0.10±0.04), but was not associated with performance over time. In reference participants, no associations were found.
CONCLUSIONS
Our findings suggest that blood-based biomarkers of AD-related pathology predict cognitive decline in patients with cardiovascular diseases.
背景
我们假设阿尔茨海默病（AD）相关病理可能会加速心血管疾病患者的认知能力下降。
目的
研究与 AD 相关的血液生物标志物、星形胶质细胞激活和神经退行性变与认知能力下降之间的关系。
方法
我们纳入了来自多中心 Heart-Brain 研究的 412 名心力衰竭、颈动脉闭塞性疾病或血管性认知障碍患者（年龄：68.6±9.0）和 128 名参考参与者（年龄：65.7±7.5）。使用 SiMoA（Quanterix）测定基线时的淀粉样蛋白-β42/40（Aβ42/40）、磷酸化 tau181（pTau181）、神经胶质纤维酸性蛋白（GFAP）和神经丝轻链（NfL）。（随访时间：2.1±0.3 年）。我们应用线性混合模型，包含生物标志物、时间和生物标志物*时间交互作用的项，调整年龄、性别、教育和地点，以评估生物标志物与认知能力下降之间的关系。
结果
在患者中，Aβ42/40 与基线时的认知表现无关。然而，较低的 Aβ42/40 与整体认知能力的下降更陡峭相关（β±SE：0.04±0.02）。较高的 pTau181 与整体认知能力（-0.14±0.04）和记忆（-0.31±0.09）的基线表现较差以及整体认知能力（-0.07±0.02）、记忆（-0.09±0.04）、注意力（-0.05±0.02）和语言（-0.10±0.03）的下降更陡峭有关。较高的 GFAP 与整体认知能力（-0.22±0.05）、记忆（-0.43±0.10）、注意力（-0.14±0.06）、语言（-0.15±0.05）和执行功能（-0.15±0.05）的基线表现较差以及整体认知能力（-0.05±0.01）的下降更陡峭有关。较高的 NfL 与整体认知能力（-0.16±0.04）、记忆（-0.28±0.09）、注意力（-0.20±0.06）和执行功能（-0.10±0.04）的基线表现较差有关，但与随时间的表现无关。在参考参与者中，未发现相关性。
结论
我们的研究结果表明，与 AD 相关的血液生物标志物可预测心血管疾病患者的认知能力下降。
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