Department of Psychiatry, University of Szeged, Szeged, Hungary.
J Alzheimers Dis. 2014;38(2):371-7. doi: 10.3233/JAD-131139.
Neurotransmitter enhancement therapy with acetylcholinesterase inhibitors (AChEIs) is a clinically proven approach for patients with Alzheimer's disease (AD). Donepezil is one of the three currently approved AChEIs for treating AD symptoms delaying the decline in cognitive function. In addition to cholinergic hypofunction, there are several factors in AD pathogenesis. For example, adipocytokines released from adipose tissue are also thought to play a role in the progress of dementia. Adipokines, i.e., leptin and adiponectin, are involved in the modulation of certain cognitive functions in the brain. The goal of our study was to elucidate effects of donepezil therapy on the serum levels of certain adipokines, such as leptin and adiponectin in AD patients. Clinically diagnosed mild-to-moderate AD patients (n = 26) were involved in this open-labeled, single-center, prospective self-control study. ApoE polymorphism, serum adiponectin, leptin, LDL, HDL, triglyceride levels, and BMI were determined before and at 12 and 24 weeks intervals of donepezil treatment, respectively. Twenty-four weeks of donepezil treatment induced a linear decrease of serum leptin levels (p = 0.013) and a linear elevation of serum adiponectin levels (p = 0.007). BMI (p < 0.001) and abdominal circumference (p = 0.017) were significantly lower at 24 weeks as compared to control values. None of the other examined metabolic parameters were changed during the treatment period. This previously unrecognized serum adipokine regulating potential of donepezil may be relevant in its therapeutic, disease modifying effect in AD by transferring protective (by increasing serum adiponectin levels) and detrimental (by decreasing serum leptin levels) effects onto the neurodegenerative process at the same time.
神经递质增强疗法，使用乙酰胆碱酯酶抑制剂（AChEIs），是一种经过临床验证的治疗阿尔茨海默病（AD）的方法。多奈哌齐是目前三种被批准用于治疗 AD 症状的 AChEIs 之一，可延缓认知功能下降。除了胆碱能功能低下外，AD 的发病机制还有其他几个因素。例如，脂肪组织释放的脂肪细胞因子也被认为在痴呆症的进展中起作用。脂肪细胞因子，即瘦素和脂联素，参与大脑某些认知功能的调节。我们的研究目的是阐明多奈哌齐治疗对 AD 患者血清中某些脂肪细胞因子（如瘦素和脂联素）水平的影响。我们纳入了这项开放标签、单中心、前瞻性自身对照研究中的 26 例临床诊断为轻中度 AD 的患者。在多奈哌齐治疗前、12 周和 24 周时，分别测定载脂蛋白 E 多态性、血清脂联素、瘦素、LDL、HDL、甘油三酯水平和 BMI。24 周的多奈哌齐治疗导致血清瘦素水平呈线性下降（p = 0.013），血清脂联素水平呈线性升高（p = 0.007）。与对照组相比，24 周时 BMI（p < 0.001）和腰围（p = 0.017）明显降低。在治疗期间，其他检查的代谢参数均无变化。多奈哌齐以前未被认识到的调节血清脂肪细胞因子的能力，可能与其在 AD 中的治疗、疾病修饰作用有关，因为它同时将保护作用（通过增加血清脂联素水平）和有害作用（通过降低血清瘦素水平）转移到神经退行性过程中。
