Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials

Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model

“…This prompted us to speculate that cholinergic stimuli also possess angiogenesis-promoting effects. ACh clearly promoted angiogenesis and acceleration of tube formation; however, it is quite difficult to apply ACh directly to an in vivo model, because ACh evokes life threatening side effects, i.e., bronchospasm, enhanced secretion, and diarrhea [27,28]. Therefore, instead of ACh, we selected donepezil, which is globally used in clinical settings without side effects and has been demonstrated to increase tissue ACh levels [9,10,21].…”

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

“…However, galantamine provided no significant benefits over placebo in patients with pure VaD. In the second larger trial, cognition and executive function were significant enhanced by galantamine compared to placebo, although fewer data were generated [45,115] . Moreover, a post-ischemic single administration of galantamine also showed a beneficial effect on the recovery of learning ability in rats [116] , which suggests a direct effect of galantamine on the early pathologic changes of CNS damage.…”

“…Cholinergic agents include ACh precursors, which increase the synthesis of ACh; nicotinic or M1 muscarinic agonists, which directly stimulate cholinergic receptors or allosterically modulate nAChR [41] ; and synaptic AChE inhibitors, which prevent the degradation of ACh. Recent preclinical and clinical evidence indicates that treatment with cholinergic agents has beneficial effects on dementia of vascular origin [42][43][44][45][46][47][48] .…”

“…In a later study, donepezil was further demonstrated to significantly improve cognitive function, global function, and activities of daily living versus placebo-treated subjects in a randomized, double-blind, placebo-controlled, 24-week clinical trial comprising 1219 patients with mild to moderate cognitive decline due to probable or possible VaD (according to the NINCDS/AIREN criteria and the Hachinski Ischemia Scale), although adverse effects were reported in the higher-dose group [71,92,94,95] . Moreover, a recent randomized double-blind trial of donepezil in CADASIL showed a significant benefit on executive function and processing speed [46] , although this result was later questioned by Schneider [45] .…”

Is It Possible to Treat Vascular Dementia?

“…Several studies have tried to determine the effect of cholinesterase inhibitors on vascular dementia, but the results are also limited and inconsistent. A recent meta-analysis of randomized controlled trials concluded that cholinesterase inhibitors and memantine produce small benefits in cognitive function and do not necessarily have clinical significance in patients with mild to moderate vascular dementia [30]. According to the authors, there are insufficient data to support widespread use of these drugs in vascular dementia.…”