Drugs that are anticholinergic-they block the brain's key neurotransmitter, acetylcholine-appear to have a direct bearing on longevity. Acetylcholine sends messages between nerve cells, and it's already known that dementia is associated with a reduction in acetycholine activity, whereas Alzheimer's drugs such as Aricept are supposed to boost activity levels.
But researchers from the University of East Anglia fear that anticholinergic drugs aren't only speeding mental decline-a fact established in earlier studies-they are also responsible for the patient's premature death.
Taking one drug with anticholinergic effects may not hasten a person's death-but a cocktail of these drugs just might. The over-65s take a third of all prescribed pharmaceuticals every year, even though they represent just 13 per cent of the population. On average, someone aged 65 and over takes six drugs a day for a variety of ailments or as a just-in-case measure, such as for lowering levels of cholesterol or high blood pressure, and many of these may be anticholinergic. Polypharmacy-as multiple-drug use is called-is even worse in hospitals and care homes, where the average rises to seven drugs a day.
The researchers have gauged the anticholinergic capacity of a wide range of drugs as part of the Medical Research Council's Cognitive Function and Ageing Studies, a project that set out to discover ways of reducing the risk of dementia and cognitive decline as we age.
The researchers recruited more than 13,000 men and women aged 65 years and older who were taking around 80 different drugs-prescription and over-the-counter ones-among them. Half the drugs were anticholinergic.
These anticholinergic drugs, which include popular painkillers such as codeine, were ranked for their effects-from one for mild to three for severe-in a measure the researchers call the 'anticholinergic burden' (ACB). Drugs with the highest ACB include the antidepressants amitriptyline and clomipramine, tranquillizers such as chlorpromazine, the bladder medication oxybutynin and anti-histamines such as chlorphenamine (see Factfile, below).
Twenty per cent of the participants taking drugs with a combined ACB score of four or more were dead by the end of the two years the study ran compared with just seven per cent of those taking drugs with a combined zero ACB score.
This was the first time that a link between anticholinergic activity and mortality has been demonstrated. The researchers also discovered that the odds of dying increased by 26 per cent for every additional point added to the ACB load (J Am Geriatr Soc,published online, June 24, 2011).
Lead researcher Dr Chris Fox said: "This is the first large-scale study into the long-term impact of medicines which block acetylcholine . . . and our results show a potentially serious effect on mortality."
In other findings, the research team confirmed discoveries made by earlier studies that anti-cholinergics also contribute to mental decline. People taking drugs with a combined ACB load of five or more recorded scores in a cognitive function test that were four per cent lower than those achieved by those taking drugs with a zero ACB score.
Researchers at the University of Florida, in Gainesville, came to similar conclusions when they assessed cognitive decline in elderly people taking a drug with anticholinergic activity. However, unlike the University of East Anglia researchers, they discovered that any anticholinergic drug could speed mental decline, regardless of whether or not it was taken as part of a cocktail of similar drugs (Proceedings of the 60th Annual Meeting of the American Academy of Neurology, Chicago, IL, 17 April 2008, Abstr, S51.001).
At the time, the drugs known to be anticholinergic were limited to medications for an overactive bladder and a few others; it has taken the latest research to uncover most-if not all-of the medications that block brain cell function.
However, other research suggests that many drugs contribute to mental decline, whether they are anticholinergic or not. Researchers at the Medical University of South Carolina, in Charleston, have discovered that almost every prescription and over-the-counter preparation can produce symptoms that resemble dementia in the elderly. Common side-effects of most medications include confusion and memory loss, and these reactions are magnified when more than one drug is taken, they found (J R Soc Med, 2000; 93:457-62).
WDDTY VOL 22, ISSUE 6
Factfile: Drugs that can cause dementia
Drugs with anticholinergic qualities according to their degree of impact (from mild to severe). Taking only one drug in the third (severe) column, or taking a combination of drugs with a combined score of 3 or higher, may have serious effects.
|ACB Score 1 (mild)||ACB Score 2 (moderate)|