Dipartimento di Neuroscienze, Salute Mentale e Organi di Senso, Sapienza Università di Roma, Italy.
IRCCS Fondazione Santa Lucia, Roma, Italy.
Curr Neuropharmacol. 2023;21(5):1214-1223. doi: 10.2174/1570159X20666220905102144.
Symptoms of cognitive impairment are rather common since the early stage of Parkinson's disease (PD); they aggravate with disease progression and may lead to dementia in a significant proportion of cases. Worsening of cognitive symptoms in PD patients depends on the progression of subcortical dopaminergic damage as well as the involvement of other brain neurotransmitter systems in cortical and subcortical regions. Beyond the negative impact on disability and quality of life, the presence and severity of cognitive symptoms may limit adjustments of dopamine replacement therapy along the disease course. This review focuses on the consequences of the administration of monoamine-oxidase type Binhibitors (MAOB-I) on cognition in PD patients. Two drugs (selegiline and rasagiline) are available for the treatment of motor symptoms of PD as monotherapy or in combination with L-DOPA or dopamine agonists in stable and fluctuating patients; a further drug (safinamide) is usable in fluctuating subjects solely. The results of available studies indicate differential effects according to disease stage and drug features. In early, non-fluctuating patients, selegiline and rasagiline ameliorated prefrontal executive functions, similarly to other dopaminergic drugs. Benefit on some executive functions was maintained in more advanced, fluctuating patients, despite the tendency of worsening prefrontal inhibitory control activity. Interestingly, high-dose safinamide improved inhibitory control in fluctuating patients. The benefit of high-dose safinamide on prefrontal inhibitory control mechanisms may stem from its dual mechanism of action, allowing reduction of excessive glutamatergic transmission, in turn secondary to increased cortical dopaminergic input.
认知障碍症状在帕金森病（PD）的早期就相当常见；随着疾病的进展，这些症状会加重，并在很大一部分病例中导致痴呆。PD 患者认知症状的恶化取决于基底节多巴胺能损伤的进展以及皮质和皮质下区域其他脑神经递质系统的参与。除了对残疾和生活质量产生负面影响外，认知症状的存在和严重程度可能会限制多巴胺替代疗法在疾病过程中的调整。这篇综述重点关注单胺氧化酶 B 抑制剂（MAOB-I）对 PD 患者认知的影响。有两种药物（司来吉兰和雷沙吉兰）可用于治疗 PD 的运动症状，作为单一疗法或与 L-DOPA 或多巴胺激动剂联合用于稳定和波动的患者；另一种药物（沙芬酰胺）仅可用于波动的患者。现有研究结果表明，根据疾病阶段和药物特点，效果存在差异。在早期、非波动的患者中，司来吉兰和雷沙吉兰改善了前额叶执行功能，与其他多巴胺能药物相似。在更晚期、波动的患者中，尽管前额叶抑制控制活动有恶化的趋势，但一些执行功能仍有改善。有趣的是，高剂量沙芬酰胺改善了波动患者的抑制控制。高剂量沙芬酰胺对前额叶抑制控制机制的益处可能源于其双重作用机制，允许减少过度的谷氨酸能传递，这反过来又继发于皮质多巴胺能输入的增加。
