Lombardi G, Lombardi N, Bettiol A, Crescioli G, Ferrari C, Lucidi G, Polito C, Berti V, Bessi V, Bagnoli S, Nacmias B, Vannacci A, Sorbi S
IRCCS Fondazione Don Carlo Gnocchi, via di Scandicci 269, 50143, Florence, Italy.
Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, viale Pieraccini 6, 50139, Florence, Italy.
Eur J Clin Pharmacol. 2022 Jul;78(7):1155-1163. doi: 10.1007/s00228-022-03325-y. Epub 2022 Apr 28.
To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression.
We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10.
At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09-0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14-0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70-0.96) were associated with a significantly lower risk of AD progression.
Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage.
评估长期使用阿尔茨海默病（AD）常用的不同药物对其临床病程的影响，并确定与AD进展延迟相关的临床和治疗因素。
我们回顾性纳入了50例在卡雷吉大学医院（佛罗伦萨）神经科就诊、随访至少24个月的患者。AD诊断根据可能/疑似AD痴呆的临床诊断标准做出，且至少有一项生物标志物支持。记录临床特征、诊断时及每6个月评估的MMSE评分，以及至少使用6个月的AD药物。进行Cox回归分析以估计AD进展的风险比（HR），将进展到更严重疾病阶段定义为MMSE评分低于10作为“最终事件”。
基线时，MMSE评分中位数为22。在随访期间（中位数为41个月），56%的患者进展到更严重疾病阶段。单独使用美金刚（HR 0.24；95%CI 0.09 - 0.60）或与乙酰胆碱酯酶抑制剂联合使用（HR 0.35；95%CI 0.14 - 0.88）以及基线时较高的MMSE评分（HR 0.82；95%CI 0.70 - 0.96）与AD进展风险显著降低相关。
目前，尚无有效的AD疾病修饰疗法。然而，当确诊后，我们的结果支持长期使用现有药物治疗的优势，尤其是联合使用，可延缓AD进展到更严重疾病阶段。
