Drug Effects on Alzheimers Patients ReassuringResearchers have added further detail to their findings on the risks of common drugs for elderly people.

Dr. Chris Fox of the University of East Anglia, UK, and colleagues found that anticholinergic drugs — which block a key neurotransmitter called acetylcholine and include many drugs often taken by older adults — may cause cognitive impairment.

Drugs which have anticholinergic activity range from antidepressants to antihistamines. They include Benadryl, Dramamine, Excedrin PM, Nytol, Sominex, Tylenol PM, and Unisom. Others available only by prescription include Paxil, Detrol, Demerol and Elavil. Older people are more at risk because they tend to be greater users of these drugs.

Now, the research team has looked in detail at these drugs’ effects on people already suffering from dementia. They studied 224 people with established Alzheimer’s disease who were taking low levels of anticholinergic drugs. The majority (71 percent) were women, and their mean age was 81 years.

The participants’ cognitive function was remeasured six and 18 months into the study using the Mini-Mental State Exam, the Severe Impairment Battery (which assesses specific behavioral and cognitive deficits associated with severe dementia), and the cognitive section of the Alzheimer’s Disease Assessment Battery. Their exposure to anticholinergic drugs also was recorded.

No differences were seen in cognitive functioning for individuals with high or low exposure to anticholinergic drugs at either six or 18 months, once cognitive function at the start was taken into account.

“Medications with anticholinergic effect in patients with Alzheimer’s disease were not found to effect deterioration in cognition,” the researchers reported.

“Our study did not support a continuing effect of these medications on people with Alzheimer’s disease who are established on them.”

Dr. Fox commented: “We found that taking a low dose of medication with a low degree of anticholinergic activity does not appear to lead to more impaired cognition or a more rapid cognitive decline in people with dementia. We hope that this will provide some reassurance to families and carers of those with dementia.”

But he added that the team is still concerned about the impact on frail older people who have no signs or mild signs of impaired cognition before they start to take the drugs. “More work is needed in this area,” he states. “In addition, we need studies on mortality in the more advanced dementia with these medicines.”

Co-author Dr. Ian Maidment of Kent University, UK, added: “One possible explanation for the different results is that in people with dementia, their cholinergic system is already impaired and therefore introducing a further insult to the cholinergic system has little effect. These results do, however, highlight the complexity of the issue and the need for further in-depth research.”

Future research also needs to assess the impact of medication doses, say the experts. The study is published in the journal Age and Ageing.

In a 2012 review of the effect of anticholinergic drugs on cognitive decline, several of the same authors explain that Alzheimer’s disease “is characterized by a cholinergic deficit in the basal forebrain.” They write that there is increasing evidence that this brain area is already affected prior to dementia, early in the course of Alzheimer’s disease.

This loss of cholinergic activity may be a crucial component since it is associated with cognitive impairment and behavioral changes in many types of dementia, they explain. And anticholinergic drugs may exacerbate the process. For example, an increase in plaque density has been observed in Parkinson’s patients treated with anticholinergics.

“The most important clinical issue,” they warn, “is that a high proportion of the older population are exposed to multiple drugs with low anticholinergic activity, and the cumulative burden of these medications over many years may be associated with accelerated cognitive decline.”

Clinicians should consider, as part of every older person’s medication review, whether each medication is necessary and whether it could and should be stopped, recommend the experts.

“One caveat to this is that people with established Alzheimer’s disease may be stable on their current medication and not exhibit, paradoxically, any medication-related decline in cognition, as the damage to their cholinergic systems has already occurred,” explain the authors, referring to their previous study. “These patients may be able to tolerate a relatively large anticholinergic load.


Fox, C. et al. The impact of anticholinergic burden in Alzheimer’s Dementia – the Laser-AD study. Age and Ageing published online September 19, 2011 doi:10.1093/ageing/afr102

Fox, C. et al. Anticholinergic medication use and cognitive impairment in the older population: the medical research council cognitive function and ageing study. Journal of the American Geriatrics Society August 2011, Vol. 59, No. 8, pp. 1477-83. doi: 10.1111/j.1532-5415.2011.03491.x.

Smithard, D. G. et al. Do anticholinergic drugs contribute to functional and cognitive decline? Aging Health February 2012, Vol. 8, No. 1, pp. 57-60, doi: 10.2217/ahe.11.87