According to a Swedish study(eurheartj.oxfordjournals.org) published recently in the European Heart Journal, use of cholinesterase inhibitors (ChEIs) to treat subjects diagnosed with mild to moderate Alzheimer's disease was associated with a reduced risk of myocardial infarction (MI) and death.
The observational study, which drew data from a cohort of more than 7,000 patients diagnosed with Alzheimer's dementia or Alzheimer's mixed dementia and enrolled in the Swedish Dementia Registry(www.ucr.uu.se), was based on the premise that the medications' anti-inflammatory properties and, perhaps, vagotonic side effects, could play a role in reducing the risk of cardiovascular disease (CVD), including MI.
In fact, study researchers found that ChEI use was associated with an approximate 35 percent reduced risk of MI or death and that the risk decreased as ChEI dosage increased.
"This risk reduction was similar in subcohorts of subjects according to different age, gender and cognitive function, presence of CVD or not, and diagnosis of Alzheimer's dementia or Alzheimer's mixed dementia," the authors wrote. "This risk reduction was also similar in case-control cohorts that were matched based on all potential confounders. The risk of both MI and death decreased with an increasing dose of ChEI.
"However, given that this is an observational study, it would be of value if the findings could be confirmed in a randomized controlled trial."
In speculating about the possible mechanisms of action underlying the cardiovascular effects found, the study authors noted that ChEIs' treatment effects on Alzheimer's disease, as demonstrated in randomized-controlled studies, "have been attributed to the reduced breakdown of acetylcholine, a neurotransmitter that has been associated with memory function, by the blockage of the enzyme acetylcholinesterase."
Previous research, they added, has documented the anti-inflammatory properties of ChEIs due to reduced acetylcholine breakdown, as well as their ability to reduce peripheral cytokine production.
"Given that atherosclerosis, which underlies most forms of CVD, is considered to be an inflammatory disease, such effects could be of interest with respect to CVD."
Of course, other, and perhaps more likely, mechanisms may contribute to the associations, the authors acknowledged. The vagotonic side effects associated with ChEI use, for example, primarily affect the gastrointestinal system, but also may "be of interest with respect to the risk of CVD," said the authors.
Overall, they concluded, "With respect to our results, effects on the cardiac system from ChEI use … could reduce oxygen demands, improve cardiac function and, thereby, reduce the risk of MI and death."