Research funded by the Medical Research Council (MRC) – the Cognitive Function and Ageing Studies (CFAS) project - has found that anticholinergic activity, an adverse effect of many commonly used medicines, appears to increase the risks of both cognitive brain impairment and death in older people. Groups of medicines with the greatest impact include: anti-depressants such as amitriptyline, imipramine and clomipramine; antipsychotics such as chlorpromazine and trifluoperazine; anti-muscarinic medication such as oxybutynin; and antihistamines such as chlorphenamine.

CFAS is a large, multi-centre initiative being led by the University of East Anglia (UEA). It was launched over 20 years ago to examine health and cognitive function in older adults. The UEA researchers worked in collaboration with the University of Cambridge, Indiana University and NHS clinicians. The current two year cohort study was initiated as part of the drive to find ways of reducing risk factors for dementia. It was conducted between 1991 and 1993 in Nottingham, Newcastle, Liverpool, Wales, Oxford and Cambridgeshire.

More than 13,000 men and women aged 65 and over from across the UK were involved in the study, half of whom were using a medication with potential anticholinergic properties. The researchers examined the medication records of participants using a tool they developed which grades levels of blockade of acetylcholine. Each drug taken by the participants was given a ranking based on the strength of its anticholinergic activity, or AntiCholinergic Burden (ACB) – 0 for no effect, 1 for mild effect, 2 for moderate effect and 3 for severe effect. The key findings were (direct from UEA source):

The key findings were:

• Twenty per cent of participants taking drugs with a total ACB of four or more had died by the end of the two-year study, compared with only 7 per cent of those taking no anticholinergic drugs.  - the first time a link between anticholinergics and mortality has been shown.
• For every additional ACB point scored, the odds of dying increased by 26 per cent.
• Participants taking drugs with a combined ACB of five or more scored more than 4 per cent lower in a cognitive function test than those taking no anticholinergic medications – confirming evidence from previous smaller studies of a link between anticholinergics and cognitive impairment.
• The increased risks from anticholinergic drugs were shown to be cumulative, based on the number of anticholinergic drugs taken and the strength of each drug’s anticholinergic effect.
• Those who were older, of lower social class, and with a greater number of health conditions tended to take the most anticholinergic drugs.

The lead researcher for the study said: “Our results show a potentially serious effect on mortality. Clinicians should conduct regular reviews of the medication taken by their older patients, both prescribed and over the counter, and wherever possible avoid prescribing multiple drugs with anticholinergic effects.” He told BBC news that he wanted to conduct further research to investigate how anticholinergic drugs might increase mortality.

Dr Clare Gerada, chairperson of the Royal College of GPs, told BBC news that the findings of the study were important. She advised patients: "The first thing is not to worry too much, the second thing is to discuss it with your doctor or the pharmacist, and the third thing is do not stop your medicines without taking advice first."

The Head of Research at the Alzheimer's Society told BBC news that a 4% drop in brain function for a healthy person would feel like a “slow, sluggish day.” She added, "If you are at a level where one little thing pushes you over into confusion, then that is much more serious. However, it is vital that people do not panic or stop taking their medication without consulting their GP."

A question and answer document is available at the UEA link below.

Nb: The study is due to be published early online in the Journal of the American Geriatrics Society and was not available at time of writing. A link to the journal homepage is provided below.