Sárkány Zsuzsa, Damásio Joana, Macedo-Ribeiro Sandra, Martins Pedro M
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Alzheimers Dement. 2025 May;21(5):e70213. doi: 10.1002/alz.70213.
This retrospective study investigates whether exposure to levodopa/carbidopa (LA/CA) medication is associated with modified Alzheimer's disease (AD) trajectories.
Multivariate analysis used cerebrospinal fluid (CSF) biomarker information included in the National Alzheimer's Coordinating Center Uniform Data Set for subjects with normal cognition (NC), mild cognitive impairment (MCI), and dementia (DE). Survival analyses examined the progression to MCI/DE and death events.
LA/CA use is associated with lower levels of CSF amyloid beta, phosphorylated-tau (p-tau) and total-tau. After adjusting for age, sex, and apolipoprotein E (APOE) ε4 allele presence, that effect was quantified by negative coefficients of the fitted linear mixed models: p-values < 0.01 in all cases except for p-tau in the MCI subgroup (p = 0.02). No similar effects were identified for other antiparkinsonians. Exposure to LA/CA decreased the progression from MCI to DE (p = 0.03).
The identified association between LA/CA exposure, AD biomarkers, and progression deserves further investigation in controlled clinical trials.
LA/CA is associated with lower levels of CSF biomarkers for AD. This effect is not observed when other antiparkinsonian drugs are used. LA/CA is also associated with delayed progression to dementia by AD patients with MCI.
这项回顾性研究调查了左旋多巴/卡比多巴（LA/CA）药物暴露是否与阿尔茨海默病（AD）病程的改变有关。
多变量分析使用了纳入国家阿尔茨海默病协调中心统一数据集的脑脊液（CSF）生物标志物信息，这些数据来自认知正常（NC）、轻度认知障碍（MCI）和痴呆（DE）的受试者。生存分析考察了进展为MCI/DE和死亡事件的情况。
使用LA/CA与较低水平的脑脊液淀粉样蛋白β、磷酸化tau蛋白（p-tau）和总tau蛋白相关。在调整年龄、性别和载脂蛋白E（APOE）ε4等位基因存在情况后，通过拟合线性混合模型的负系数对该效应进行了量化：除MCI亚组中的p-tau外（p = 0.02），所有情况下p值均<0.01。未发现其他抗帕金森药物有类似效应。暴露于LA/CA可降低从MCI进展为DE的发生率（p = 0.03）。
LA/CA暴露、AD生物标志物与疾病进展之间已确定的关联值得在对照临床试验中进一步研究。
LA/CA与较低水平的AD脑脊液生物标志物相关。使用其他抗帕金森药物时未观察到这种效应。LA/CA还与MCI的AD患者痴呆进展延迟有关。
