阿尔茨海默病合并慢性阻塞性肺疾病患者神经递质水平与认知功能的相关性

Correlation between neurotransmitter levels and cognitive function in patients with comorbid Alzheimer's disease and chronic obstructive pulmonary disease

中文关键词:  阿尔茨海默病  慢性阻塞性肺疾病  神经递质  认知功能

英文关键词:Alzheimer's disease  Chronic obstructive pulmonary disease  Neurotransmitters  Cognitive function

中文摘要:

      背景 随着人口老龄化加剧，阿尔茨海默病（AD）患病率逐年升高，其中10%~20%的AD患者同时患有慢性阻塞性肺疾病（COPD）。与单纯AD或COPD患者相比，AD合并COPD患者表现出更严重的认知功能受损、生活质量降低以及疾病负担加重。AD和COPD患者均存在神经递质水平异常，并影响认知功能，但在AD和COPD共病状态下，神经递质水平与认知功能的关系尚不明确。目的 分析AD合并COPD患者的神经递质水平与认知功能的关系，为改善AD合并COPD患者的认知功能提供参考。方法 纳入2024年1月—9月在绵阳市第三人民医院住院治疗的、符合《国际疾病分类（第10版）》AD诊断标准的患者40例为AD组，符合《慢性阻塞性肺疾病全球倡议指南（2023）》COPD诊断标准的患者40例为COPD组，同时符合AD诊断标准及COPD诊断标准的患者40例为AD合并COPD组。同期选择40名在该院体检且身体健康者为对照组。采用脑涨落图仪检测γ-氨基丁酸（GABA）、谷氨酸（Glu）、去甲肾上腺素（NE）、5-羟色胺（5-HT）、乙酰胆碱（Ach）、多巴胺（DA）水平。通过简易精神状态评价量表（MMSE）和蒙特利尔认知评估量表（MoCA）评定认知功能。采用Spearman相关分析考查AD合并COPD患者神经递质水平与认知功能的相关性。采用多元线性回归分析考查AD合并COPD患者认知功能的影响因素。结果 ①四组MMSE和MoCA评分比较，差异均有统计学意义（H=126.323、128.489，P均<0.01）。AD合并COPD组MMSE和MoCA评分均低于COPD组、AD组和对照组，差异均有统计学意义（P均<0.05）。②四组GABA、Glu、Ach、NE、DA水平比较，差异均有统计学意义（H=61.094、46.665、135.289、15.089、129.636，P均<0.01）。与COPD组、AD组和对照组相比，AD合并COPD组的GABA、Ach、DA水平更低，Glu水平更高，差异均有统计学意义（P均<0.05）。③AD合并COPD组的GABA、Ach、DA水平与MMSE评分均呈正相关（r=0.633、0.876、0.580，P均<0.05），Glu水平与MMSE评分呈负相关（r=-0.377，P=0.013）。④Ach水平（B=0.253，95% CI：0.153~0.352）、GABA水平（B=0.137，95% CI：0.013~0.261）、年龄（B=-0.212，95% CI：-0.356~-0.069）以及受教育年限（B=-0.367，95% CI：-0.608~-0.126）是AD合并COPD患者认知功能的影响因素。结论 与COPD组、AD组和对照组相比，AD合并COPD患者的认知功能受损更严重，且GABA、Ach、DA水平更低，Glu水平更高；Ach和GABA水平可能是AD合并COPD患者认知功能的潜在影响因素。

英文摘要:

      Background With the intensification of population aging， the prevalence of Alzheimer's disease （AD） has been increasing， and 10% to 20% of AD patients also suffer from chronic obstructive pulmonary disease （COPD）. Compared to patients with a single disease， those with comorbid AD and COPD show more severe cognitive impairment， reduced quality of life， and a greater disease burden. Both AD and COPD patients exhibit abnormal levels of neurotransmitters， which affect cognitive function. However， the alterations in neurotransmitter levels in patients with comorbid AD and COPD and their association with cognitive function remain unclear.Objective To analyze the relationship between neurotransmitter levels and cognitive function in patients with AD combined with COPD， and to provide references for improving the cognitive function in this population.Methods A total of 120 patients who were hospitalized at The Third Hospital of Mianyang from January to September 2024 were divided into three groups： 40 patients meeting the International Classification of Diseases， tenth edition （ICD-10） diagnostic criteria for AD were defined as AD group， 40 patients meeting the diagnostic criteria for COPD according to the Global Initiative for Chronic Obstructive Lung Disease （GOLD） 2023 guidelines were defined as COPD group， another 40 patients meeting the diagnostic criteria for both conditions were defined as AD combined with COPD group. Additionally， 40 healthy individuals undergoing physical examination at the same hospital during the same period were selected as the control group. Encephalofluctuograph was used to detect the levels of γ-aminobutyric acid （GABA）， glutamate （Glu）， norepinephrine （NE）， 5-hydroxytryptamin （5-HT）， acetylcholine （Ach）， and dopamine （DA）. Cognitive function of the subjects was assessed using the Mini-Mental State Examination （MMSE） and the Montreal Cognitive Assessment （MoCA）. Spearman correlation analysis was used to investigate the correlation between neurotransmitter levels and cognitive function in AD combined with COPD patients. Multiple linear regression analysis was adopted to investigate the influencing factors of cognitive function in this population.Results ①Significant differences were observed in MMSE and MoCA scores across all four groups （H=126.323， 128.489， P<0.01）. The AD combined with COPD group demonstrated significantly lower MMSE and MoCA scores compared with COPD group， AD group， and control group （P<0.05）. ②Statistically significant differences were found in the levels of GABA， Glu， Ach， NE，and DA among the four groups （H=61.094， 46.665， 135.289， 15.089， 129.636， P<0.01）. Compared with the COPD group， AD group， and control group， the AD combined with COPD group showed significantly lower levels of GABA， Ach， and DA， but higher Glu levels， with all differences being statistically significant （P<0.05）. ③In the AD combined with COPD group， the levels of GABA， Ach， and DA showed positive correlations with MMSE scores （r=0.633， 0.876， 0.580， P<0.05）， while Glu levels were negatively correlated with MMSE scores （r=-0.377， P=0.013）. ④The levels of Ach （B=0.253， 95% CI： 0.153–0.352）， GABA （B=0.137， 95% CI： 0.013–0.261）， age （B=-0.212， 95% CI： -0.356–-0.069） and education duration （B=-0.367， 95% CI： -0.608–-0.126） were the influencing factors of cognitive function in patients with AD combined with COPD.Conclusion Compared with the COPD group， AD group， and control group， patients with AD combined with COPD exhibited more severe cognitive impairment， along with lower levels of GABA， ACh， and DA， but higher Glu levels. Ach and GABA levels are potential influencing factors of cognitive function in AD combined with COPD patients.