Pistorio Sabrina, Scotto di Tella Gianluca, Canzanella Vittoria, Merenda Raffaella, Cuomo Gianluigi, Iacotucci Paola, Carnovale Vincenzo, Bencivenga Leonardo, Vargas Maria, Manes Annalaura, Cataldi Mauro, Rengo Giuseppe, Zanetti Michela, Femminella Grazia Daniela
Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy.
Front Med (Lausanne). 2025 Feb 12;12:1505007. doi: 10.3389/fmed.2025.1505007. eCollection 2025.
Drugs with anticholinergic properties are frequently prescribed to patients with cognitive impairment. The cholinergic system plays an important role in learning processes, memory, and emotions regulation. The aim of this research is to report use of anticholinergic drugs in a clinical population and to investigate the correlation between the use of anticholinergic drugs and the risk of presenting with more severe behavioral and psychological symptoms (BPSD).
Patients with a diagnosis of subjective cognitive impairment, mild cognitive impairment (MCI) or dementia were recruited. Screening tests for cognitive impairment (MMSE) and functional status (ADL, IADL) were performed. BPSD were evaluated with the Neuropsychiatric Inventory (NPI). The anticholinergic burden was calculated using the ACB calculator. We compared patients at low risk of anticholinergic adverse effects (ACB < 3) versus patients at high risk (ACB ≥ 3). Chi-square test and Mann-Whitney test were used to compare the two groups. A multiple linear regression was performed to identify factors associated with higher NPI score and a logistic regression model was built to identify drug classes associated with ACB ≥ 3.
A total of 173 patients (mean age 74 ± 7, 74 men) were included in the study; 132 patients with ACB < 3 (low risk) versus 41 patients with ACB ≥3 (high risk) were compared. No statistically significant differences were found between the two groups in terms of demographics (age, sex) and anamnestic variables (education, marital status, family history of dementia, hypertension, diabetes, smoking, dyslipidemia, atrial fibrillation, coronary heart disease and use of alcohol). Significantly higher NPI scores were found in patients with ACB ≥ 3 (mean scores 47.3 ± 34.8 versus 25.5 ± 24.6, < 0.001). Patients with ACB ≥ 3 showed lower MMSE (18.5 ± 8.6 versus 22.4 ± 7, = 0.004) and more IADLs lost. In the multivariate regression analysis, after adjusting for age, sex, polypharmacy and IADLs lost, only the MMSE and the ACB scores were independent predictors of the NPI score. Being on antipsychotics, antidepressants and antidiabetic drugs was associated with increased risk of higher anticholinergic burden.
In conclusion, the anticholinergic burden might play a significant role as a risk factor for developing more severe BPSD in patients with cognitive decline, independently from their degree of cognitive impairment.
具有抗胆碱能特性的药物经常被开给认知障碍患者。胆碱能系统在学习过程、记忆和情绪调节中起着重要作用。本研究的目的是报告临床人群中抗胆碱能药物的使用情况，并调查抗胆碱能药物的使用与出现更严重的行为和心理症状（BPSD）风险之间的相关性。
招募诊断为轻度认知障碍、轻度认知障碍（MCI）或痴呆的患者。进行认知障碍筛查测试（MMSE）和功能状态评估（ADL、IADL）。使用神经精神科问卷（NPI）评估BPSD。使用抗胆碱能负担计算器计算抗胆碱能负担。我们比较了抗胆碱能不良反应低风险患者（ACB＜3）和高风险患者（ACB≥3）。采用卡方检验和曼-惠特尼检验比较两组。进行多元线性回归以确定与较高NPI评分相关的因素，并建立逻辑回归模型以确定与ACB≥3相关的药物类别。
本研究共纳入173例患者（平均年龄74±7岁，男性74例）；比较了132例ACB＜3的低风险患者和41例ACB≥3的高风险患者。两组在人口统计学特征（年龄、性别）和既往史变量（教育程度、婚姻状况、痴呆家族史、高血压、糖尿病、吸烟、血脂异常、心房颤动、冠心病和饮酒情况）方面未发现统计学显著差异。ACB≥3的患者NPI评分显著更高（平均评分47.3±34.8对25.5±24.6，P＜0.001）。ACB≥3的患者MMSE评分更低（18.5±8.6对22.4±7，P = 0.004），且失去更多IADL能力。在多变量回归分析中，在调整年龄、性别、多种药物联用和失去的IADL能力后，只有MMSE评分和ACB评分是NPI评分的独立预测因素。使用抗精神病药物、抗抑郁药物和抗糖尿病药物与抗胆碱能负担增加的风险相关。
总之，抗胆碱能负担可能作为认知功能下降患者发生更严重BPSD的风险因素发挥重要作用，独立于其认知障碍程度。
