Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment

Abstract

Vascular dementia (VaD) is a progressive neurodegenerative disease with a high prevalence. Several studies have recently reported that VaD patients present cholinergic deficits in the brain and cerebrospinal fluid (CSF) that may be closely related to the pathophysiology of cognitive impairment. Moreover, cholinergic therapies have shown promising effects on cognitive improvement in VaD patients. The precise mechanisms of these cholinergic agents are currently not fully understood; however, accumulating evidence indicates that these drugs may act through the cholinergic anti-inflammatory pathway, in which the efferent vagus nerve signals suppress pro-inflammatory cytokine release and inhibit inflammation, although regulation of oxidative stress and energy metabolism, alleviation of apoptosis may also be involved. In this paper, we provide a brief overview of the cholinergic treatment strategy for VaD and its relevant mechanisms of anti-inflammation.

Is There a Specific Pattern of Attention Deficit in Mild Cognitive Impairment with Subcortical Vascular Features? Evidence from the Attention Network Test

“…It is likely that the subcortical vascular damage in these patients impaired the cholinergic system and thereby affected covert orienting responses of attention, which are modulated by acetylcholine (Ach) [8]. The vascular determinants of cholinergic deficits in vascular dementia (VaD) patients have been widely investigated and discussed in the literature [18,19]. Animal models attempting to reproduce VaD consistently reveal decreases in cholinergic markers [18,19].…”

“…The vascular determinants of cholinergic deficits in vascular dementia (VaD) patients have been widely investigated and discussed in the literature [18,19]. Animal models attempting to reproduce VaD consistently reveal decreases in cholinergic markers [18,19]. Postmortem studies in animals have also shown significant reductions in choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity following chronic (rather than acute) vascular damage [20,21].…”

Paeoniflorin attenuates hippocampal damage in a rat model of vascular dementia

“…As the population ages and cerebrovascular disease prevalence increases, the occurrence of VD increases as well (6). Etiopathogenic mechanisms causing VD include oxidative stress, cytotoxicity of reactive oxygen species, mitochondrial dysfunction and apoptosis (7,8). The rat bilateral common carotid artery occlusion (BCCAO) model is the most common model used to investigate the effect of chronic cerebral hypoperfusion-induced cognitive dysfunction, and is used to screen drugs with potential therapeutic value for VD (9).…”

Mulberry Fruits Extract Mitigate Vascular Dementia

“…It was found that level of oxidative stress markers such as Malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) (Shi et al, 2012) were elevated while the antioxidant systems such as the level of vitamin E (Ryglewicz et al, 2002) were decreased in VaD patients (Gustaw-Rothenberg et al, 2010). In addition, the cholinergic system was also reported to involve in cognitive impairment in VaD (Roman, 2005;Wang et al, 2009). Current approaches to dementia-related neurodegenerative diseases still highly rely on relieving symptoms.…”