Almkvist O, Darreh-Shori T, Stefanova E, Spiegel R, Nordberg A
Neurotec Department, Karolinska Institutet, Stockholm, Sweden.
Eur J Neurol. 2004 Apr;11(4):253-61. doi: 10.1046/j.1468-1331.2003.00757.x.
Cholinesterase inhibitors (ChEIs) have shown positive symptomatic effects on cognition, activities of daily living, and behavior in patients with Alzheimer's disease (AD). Rivastigmine is a slowly reversible ChEI that inhibits acetylcholinesterase and butyrylcholinesterase. We evaluated the effects of long-term rivastigmine treatment on cognitive function and plasma levels of ChE activity, and the relationship between ChE activity and cognition. Patients with mild AD (n = 11) treated with rivastigmine for 12 months were compared with matched groups of untreated patients with AD (n = 21) or mild cognitive impairment (MCI; n = 22) representing the natural course of the pre-clinical and very early stage of disease. For untreated AD patients, neuropsychological assessment was made at baseline and 12 months. Determination of ChE activity in plasma and assessment of global cognition, episodic memory, visuospatial ability, and attention were performed at 0 (baseline), 3, 6, and 12 months for treated AD patients and untreated MCI patients. At 12 months, cognitive function was slightly improved or maintained in mild AD patients treated with rivastigmine. In contrast, cognition was markedly worsened in untreated AD patients and unchanged or slightly worsened in untreated MCI patients. In the group of treated AD patients, there was a significant correlation between plasma ChE inhibition and cognition, particularly in relation to attention. This effect was most apparent at 3 months of treatment. In conclusion, a clear beneficial effect of rivastigmine was shown on cognitive function for patients with mild AD and plasma values of ChE inhibition were associated with attention.
胆碱酯酶抑制剂(ChEIs)已在阿尔茨海默病(AD)患者的认知、日常生活活动及行为方面显示出积极的症状改善作用。利伐斯的明是一种可逆性较慢的胆碱酯酶抑制剂,可抑制乙酰胆碱酯酶和丁酰胆碱酯酶。我们评估了长期使用利伐斯的明治疗对认知功能及血浆胆碱酯酶(ChE)活性水平的影响,以及ChE活性与认知之间的关系。将11例接受利伐斯的明治疗12个月的轻度AD患者与未治疗的AD患者匹配组(21例)或轻度认知障碍(MCI;22例)进行比较,MCI组代表疾病临床前期和极早期的自然病程。对于未治疗的AD患者,在基线和12个月时进行神经心理学评估。对接受治疗的AD患者和未治疗的MCI患者,在0(基线)、3、6和12个月时测定血浆ChE活性,并评估整体认知、情景记忆、视觉空间能力和注意力。12个月时,接受利伐斯的明治疗的轻度AD患者认知功能略有改善或维持稳定。相比之下,未治疗的AD患者认知明显恶化,未治疗的MCI患者认知无变化或略有恶化。在接受治疗的AD患者组中,血浆ChE抑制与认知之间存在显著相关性,尤其是在注意力方面。这种效应在治疗3个月时最为明显。总之,利伐斯的明对轻度AD患者的认知功能显示出明显的有益作用,血浆ChE抑制值与注意力相关。