Introduction: The most frequent dementia is senile dementia or Alzheimer disease. Meanwhile, antiCholinergic drugs can potentially modify the risk factors. As different studies have achieved dissimilar results and the clinical findings of these interventions have not been conclusive, the objective of this research will be to evaluate the effect of antiCholinergic drugs on the risk of dementia.  Methods: This systematic review and meta-analysis with no language limitation will search WoS, EMBASE, and MEDLINE via PubMed, Scopus, ProQuest electronic databases, and Grey Literature between December 15, 1988, and December 15, 2021. Our search strategy with suitability criteria covers cohort, case-control, nested case-control, randomized, and non-randomized clinical trial studies evaluating the effect of antiCholinergic drugs on the risk of dementia. Two authors will independently implement the selection phase, data extraction, and quality assessment. The reviewers will evaluate the risk of bias using the Newcastle-Ottawa, Cochrane risk of bias tool and ROBINS-I (risk of bias in non-randomized studies - of interventions)  quality assessment scale. We will conduct a meta-analysis with a random or fixed effect model according to the severity of methodological heterogeneity. The results will be presented via the forest plot for the final studies’ data composition, demonstrating the separated and combined frequency and their corresponding 95% CIs, summary tables, and narrative summaries.  Conclusion: The results of different studies in this field are various. This study’s findings and other studies will help physicians and other health professionals before prescribing these drugs. Older people, especially those with polypharmacy, should be carefully assessed for the risk of dementia, Alzheimer or a variety of cognitive disorders.

In the present study, the effects of the histamine and Cholinergic systems on memory retention in adult male rats were investigated. Post-training intracerebroventricular injections were carried out in all the experiments. Cholinoceptor agonists, acetylcholine (1-10 mg/rat) or nicotine (1-10 mg/rat) increased, while a cholinoceptor antagonist, scopolamine (5-20 mg/rat), decreased memory retention. The response to acetylcholine was attenuated by scopolamine. Administration of histamine (5-20 mg/rat) reduced, but the histamine H1 receptor antagonist, pyrilamine (10-50 mg/rat), and the histamine H2 receptor antagonist, cimetidine (1-50 mg/rat) increased memory retention in rats. The histamine receptor antagonists attenuated the response to histamine. Histamine reduced the acetylcholine- or nicotine-induced enhancement. The histamine receptor antagonists enhanced the nicotine- or acetylcholine-induced response. Histamine potentiated the inhibitory effect induced by scopolamine. It is concluded that histaminergic and Cholinergic systems have opposing effects on memory retention. Also, the histaminergic system elicits an interaction with the Cholinergic system in memory retention.

The present study investigated the effects of microinjections of acetylcholine (a Cholinergic agonist), physostigmine (a cholinesterase inhibitor), atropine (an antagonist of muscarinic Cholinergic receptors) and hexamethonium (an antagonist of nicotinic Cholinergic receptors) into the parafascicular nucleus of thalamus on the acute corneal nociception in rats. Acute corneal nociception was induced by putting a drop of 5 M NaCl solution onto the corneal surface of the eye and the number of eye wipes was counted during the first 30s. Both acetylcholine and physostigmine at the same doses of 0.5, 1 and 2 mg significantly (P<0.05) reduced the number of eye wipes. The intensity of corneal nociception was not changed when atropine and hexamethonium were used alone. Atropine (4 mg), but not hexamethonium (4 mg) significantly (P<0.05) prevented acetylcholine (2 mg) - and physostigmine (2 mg) -induced antinociceptive effects. The results indicated that at the level of the parafascicular nucleus of thalamus, the muscarinic Cholinergic receptors might be involved in the antinociceptive effects of acetylcholine and physostigmine.

Introduction: Recent studies suggest that glucocorticoids modulate memory reconsolidation. Moreover, Cholinergic system is involved in memory reconsolidation. Since glucocorticoids interact with brain Cholinergic system in modulating memory processing, we investigated whether glucocorticoid influences on the reconsolidation of emotionally arousing training depend on the Cholinergic system.Methods: Mice were trained (1mA, 3s footshock) in an inhibitory avoidance task. Forty-eight hours after training, memory reactivation was occurred (Test 1), and different treatments were given. Two (Test 2), five (Test 3), and seven days (Test 4) after memory reactivation (Test 1), animals were retested for fear memory retention.Results: In the first experiment, we observed that administration of corticosterone (CORT, 0.3, 1 and 3 mg/kg) following memory reactivation impaired subsequent expression of memory in a dose-dependent manner. In the second experiment, we found that CORT-induced impairment of memory reconsolidation was reversed by the muscarinic receptor antagonist atropine (0.5 and 2 mg/kg). In the third experiment, the nicotinic receptor antagonist mecaylamine (0.5 or 2 mg/kg) was not able to block the corticosterone response.Discussion: These findings indicate that glucocorticoids impair memory reconsolidation by a muscarinic Cholinergic mechanism.

The Cholinergic anti-inflammatory pathway (CAP) first described by Wang et al, 2003 has contemporary interest arising from the COVID-19 pandemic. While tobacco smoking has been considered an aggravating factor in the severity of COVID-19 infections, it has been suggested by some that the nicotine derived from tobacco could lessen the severity of COVID-19 infections. This spotlight briefly describes the CAP and its potential role as a therapeutic target for the treatment of COVID-19 infections using vagus nerve stimulation or selective alpha7 nicotinic acetylcholine receptor agonists.