Paradoxical effect of dopamine medication on cognition in Parkinson's disease: relationship to side of motor onset.
Paradoxical effect of dopamine medication on cognition in Parkinson's disease: relationship to side of motor onset.
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DOI：
10.1017/s1355617715000181
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Lyons KE
中科院分区：
文献类型：
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作者：
Hanna-Pladdy B;Pahwa R;Lyons KE
帕金森病(PD)的特点是出现不对称的运动症状，归因于患侧对侧多巴胺神经元的更大程度的变性。然而，运动不对称是否预测帕金森病患者的认知特征，以及多巴胺在多大程度上影响认知仍然存在争议。这项研究通过测量基于大脑半球不对称的多巴胺替代疗法(DRT)的不同反应来评估帕金森病的认知变异性。对36例有左侧或右侧运动性发作症状的轻度帕金森病患者进行DRT对认知功能的影响。所有受试者接受DRT前后的神经心理学测量，并与对照组(n=42)进行比较。帕金森病患者的执行、记忆和运动领域受损，与运动发作的一侧无关，尽管左脑功能障碍的患者表现出更严重的认知障碍。右脑功能障碍患者接受DRT治疗后，感觉运动障碍明显改善，注意力和言语记忆功能也相应改善。相反，左半球多巴胺严重缺乏的患者在接受DRT后，注意力功能没有改善，言语记忆能力下降。这些发现支持早期帕金森病患者存在广泛的轻度认知缺陷，而单靠多巴胺耗竭并不能完全解释这一点。通过反映多巴胺耗竭程度的精细运动损伤程度和对左旋多巴的感觉运动反应来预测左旋多巴对言语记忆的矛盾影响。这些发现针对影响早期帕金森病患者不同认知特征的因素进行了讨论，包括大脑半球的不对称性和基于预测改善或过量用药的多巴胺水平对左旋多巴的差异反应。
Parkinson's disease (PD) is characterized by asymmetric motor symptom onset attributed to greater degeneration of dopamine neurons contralateral to the affected side. However, whether motor asymmetries predict cognitive profiles in PD, and to what extent dopamine influences cognition remains controversial. This study evaluated cognitive variability in PD by measuring differential response to dopamine replacement therapy (DRT) based on hemispheric asymmetries. The influence of DRT on cognition was evaluated in mild PD patients (n = 36) with left or right motor onset symptoms. All subjects were evaluated on neuropsychological measures on and off DRT and compared to controls (n = 42). PD patients were impaired in executive, memory and motor domains irrespective of side of motor onset, although patients with left hemisphere deficit displayed greater cognitive impairment. Patients with right hemisphere deficit responded to DRT with significant improvement in sensorimotor deficits, and with corresponding improvement in attention and verbal memory functions. Conversely, patients with greater left hemisphere dopamine deficiency did not improve in attentional functions and declined in verbal memory recall following DRT. These findings support the presence of extensive mild cognitive deficits in early PD not fully explained by dopamine depletion alone. The paradoxical effects of levodopa on verbal memory were predicted by extent of fine motor impairment and sensorimotor response to levodopa, which reflects extent of dopamine depletion. The findings are discussed with respect to factors influencing variable cognitive profiles in early PD, including hemispheric asymmetries and differential response to levodopa based on dopamine levels predicting amelioration or overdosing.