Serum Adipokine Levels Modified by Donepezil Treatment in Alzheimer's Disease

Abstract

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.

Role of insulin impairment, adiponectin and dyslipidemia in peripheral and central neuropathy in mice

“…Another study did not find any significant difference between individuals with AD and control subjects (Warren et al, 2012), whereas others found that serum levels of adiponectin were significantly lower in individuals with mild cognitive impairment (MCI) or AD compared with control subjects (Teixeira et al, 2013). In addition, in AD patients, donepezil, one of the currently approved treatments for AD, restored plasma adiponectin levels (Pákáski et al, 2014). In our study, adiponectin levels were significantly decreased in the plasma of Swiss Webster mice but not in C57 mice that did not experience learning deficits.…”

Potential Neuroprotective Effects of Adiponectin in Alzheimer’s Disease

“…Donepezil is one of the four acetylcholinesterase inhibitors that are marketed drugs for the symptomatic treatment of AD. Intriguingly, the serum adiponectin levels progressively increased in AD patients who were administered with Donepezil [91]. Adiponectin has been considered as a therapeutic target to treat metabolic syndromes because of its potent protective effects to both the CNS and peripheral tissues.…”

Importance of adiponectin activity in the pathogenesis of Alzheimer's disease

“…Inhibition of tau aggregation may be an efficient strategy to inhibit sequestration of APN by tau, and a clinical study of tau immunization for progressive supranuclear palsy is ongoing 68. However, stimulating endogenous production of APN using compounds such as PPAR‐ γ agonists,69 acetylcholinesterase inhibitors,70 and vitamin E71 may be detrimental in terms of the toxic gain of function of APN.…”