Nair Ajay Kumar, Van Hulle Carol A, Bendlin Barbara B, Zetterberg Henrik, Blennow Kaj, Wild Norbert, Kollmorgen Gwendlyn, Suridjan Ivonne, Busse William W, Rosenkranz Melissa A
Center for Healthy Minds University of Wisconsin-Madison Madison Wisconsin USA.
Wisconsin Alzheimer's Disease Research Center School of Medicine and Public Health University of Wisconsin-Madison Madison Wisconsin USA.
Alzheimers Dement (N Y). 2022 Jul 8;8(1):e12315. doi: 10.1002/trc2.12315. eCollection 2022.
Evidence from epidemiology, neuroimaging, and animal models indicates that asthma adversely affects the brain, but the nature and extent of neuropathophysiological impact remain unclear.
We tested the hypothesis that asthma is a risk factor for dementia by comparing cognitive performance and cerebrospinal fluid biomarkers of glial activation/neuroinflammation, neurodegeneration, and Alzheimer's disease (AD) pathology in 60 participants with asthma to 315 non-asthma age-matched control participants (45-93 years), in a sample enriched for AD risk.
Participants with severe asthma had higher neurogranin concentrations compared to controls and those with mild asthma. Positive relationships between cardiovascular risk and concentrations of neurogranin and α-synuclein were amplified in severe asthma. Severe asthma also amplified the deleterious associations that apolipoprotein E ε4 carrier status, cardiovascular risk, and phosphorylated tau/amyloid beta have with rate of cognitive decline.
Our data suggest that severe asthma is associated with synaptic degeneration and may compound risk for dementia posed by cardiovascular disease and genetic predisposition.
Those with severe asthma showed evidence of higher dementia risk than controls evidenced by: higher levels of the synaptic degeneration biomarker neurogranin regardless of cognitive status, cardiovascular or genetic risk, and controlling for demographics.steeper increase in levels of synaptic degeneration biomarkers neurogranin and α-synuclein with increasing cardiovascular risk.accelerated cognitive decline with higher cardiovascular risk, genetic predisposition, or pathological tau.
来自流行病学、神经影像学和动物模型的证据表明，哮喘会对大脑产生不利影响，但神经病理生理学影响的性质和程度仍不清楚。
我们通过比较60名哮喘患者与315名年龄匹配的非哮喘对照参与者（45 - 93岁）的认知表现以及神经胶质细胞激活/神经炎症、神经退行性变和阿尔茨海默病（AD）病理的脑脊液生物标志物，来检验哮喘是痴呆症风险因素这一假设，该样本富含AD风险。
与对照组和轻度哮喘患者相比，重度哮喘患者的神经颗粒素浓度更高。在重度哮喘中，心血管风险与神经颗粒素和α - 突触核蛋白浓度之间的正相关关系被放大。重度哮喘还放大了载脂蛋白E ε4携带者状态、心血管风险以及磷酸化tau蛋白/淀粉样β蛋白与认知衰退率之间的有害关联。
我们的数据表明，重度哮喘与突触退化有关，可能会增加心血管疾病和遗传易感性导致的痴呆症风险。
重度哮喘患者比对照组表现出更高痴呆风险的证据包括：无论认知状态、心血管或遗传风险如何，且在控制人口统计学因素后，突触退化生物标志物神经颗粒素水平更高。随着心血管风险增加，突触退化生物标志物神经颗粒素和α - 突触核蛋白水平急剧上升。心血管风险较高、遗传易感性或病理性tau蛋白会加速认知衰退。
