this manifestation , widely known as post - operative cognitive dysfunction ( pocd ) , is characterized by disordered thinking and impaired consciousness with later onset and fluctuating course [ 24 ] .
pocd , as mentioned above , is common in elderly patients , and probably has a pathogenesis similar to that of ad and may even evolve into ad .
unfortunately , it has been demonstrated that 41.4% of aged patients have pocd at hospital discharge .
leptin is synthesized and secreted by adipocytes , and has been recognized as having an important role in coordinating the peripheral and central signals , ultimately regulating food intake and body weight [ 811 ] . although the biological effects of leptin are thought to regulate eating behavior and energy expenditure , a prospective clinical study with 785 participants showed that higher circulating levels of leptin contribute to reduce ad incidence .
a preclinical study has shown that leptin can reduce pathology and improve memory in a transgenic mouse model of ad .
collectively , these findings indicate that leptin has unique therapeutic effects on cognitive dysfunction , which is the primary pathological feature of ad .
in addition to pocd , it is also characterized by cognitive dysfunction and shares similar pathogenesis with ad .
we hypothesized that leptin has prophylactic and therapeutic effects on pocd , and that the leptin signaling pathway may be involved in the pathogenesis of pocd . a previous study by doherty et al
.   indicated that leptin prevents hippocampal synaptic disruption and neuronal cell death induced by amyloid- ( a ) . a study by marwarha et al .  
has shown that leptin treatment reversed the 27-hydroxycholesterol - induced increase in a and tau phosphorylation ( p - tau ) .
ad , a progressive neurodegenerative disease , is characterized by the accumulation of a peptide - containing neuritic plaques and neurofibrillary tangles composed of p - tau . in this
regard , pocd is also characterized by abnormal deposition of a and p - tau .
these findings strongly support the hypothesis that leptin may have beneficial effects for the treatment of pocd by down - regulation of a and dephosphorylation of p - tau .
amp - activated protein kinase ( ampk ) , a ser / thr kinase , has a critical role in the maintenance of energy metabolism at cellular and body levels .
furthermore , leptin is capable of decreasing the levels of tau phosphorylation by activation of ampk in rat cortical neurons .
it is widely known that pocd and ad are both aging - related diseases , and slowing the aging process may have therapeutic effects .
ampk is a major regulator , which can activate the autophagic pathway , while activation of ampk inhibits mtor , an inducer of autophagy .
our recent study proposed a hypothesis that inhibiting mtor activates the autophagic pathway , thereby leading to therapeutic effects for pocd .
leptin probably has prophylactic and therapeutic effects in pocd , and the leptin signaling pathway may be involved in the pathogenesis of pocd .
further investigations are needed to determine whether leptin has unique effects in the treatment of pocd , and to make certain whether leptin signaling pathway is involved in the pathogenesis of pocd .
 leptin plays a critical role in neuronal development and also promotes structural and functional activities in the central nervous system . 
 recent studies have demonstrated that leptin could produce therapeutic effects for cognitive impairments of patients with alzheimer s disease ( ad ) . 
 post - operative cognitive dysfunction ( pocd ) , defined as a significant dysfunction in cognitive performance for several weeks after surgery , probably has a pathogenesis similar to that of ad . 
 specifically , they are both characterized by cognitive impairment . in this regard 
 , we hypothesized that leptin probably has a therapeutic benefit of alleviating symptoms of patients with pocd , and the leptin signaling pathway may be involved in the pathogenesis of pocd . 
Background
Hypothesis
Conclusions