Anticholinergic Drugs May Increase Cognitive Decline

["M.Schild" <mmoo@xxxxxxxxxxxxxxxx>]

Anticholinergic Drugs May Increase Cognitive Decline 

  
Susan Jeffrey  
Medscape Medical News 2008. Â 2008 Medscape 
 
 April 18, 2008 (Chicago, Illinois) â A new study finds that the use of drugs 
with anticholinergic activity is associated with a more rapid decline in 
cognitive performance in older individuals.  
The findings suggest that physicians should take this possible effect into 
account when prescribing anticholinergic medication or drugs that have 
anticholinergic properties, said lead author Jack Tsao, MD, DPhil, associate 
professor of neurology at Uniformed Services University, in Bethesda, 
Maryland. 
Dr. Tsao presented the results here at the American Academy of Neurology 60th 
Annual Meeting. 
Anticholinergic Properties
Their study arose from experience with a patient seen by study coauthor 
Kenneth Heilman, MD, from the University of Florida at Gainesville, Dr. Tsao 
told Medscape Neurology & Neurosurgery. The woman had come in with memory 
complaints and hallucinations. However, Dr. Tsao said, "Her cognitive testing 
was essentially normal except for the memory issues, so she didn't fit the 
diagnosis of Alzheimer's-type dementia."
This patient had just begun treatment with tolterodine (Detrol, Pfizer) a drug 
to treat overactive-bladder problems. "Because Dr. Heilman had seen a 
previous case of another woman who had memory complaints that reversed after 
stopping her bladder medicine, we did the same for this lady, and her memory 
improved," he said. "This prompted us to ask the question of whether 
anticholinergic medicines or medicines that have anticholinergic properties 
actually can impair thinking in normal individuals."
Anticholinergic drugs range from the overactive-bladder agents and the 
Parkinson's-disease agents that are known to be strongly anticholinergic, to 
drugs such as warfarin, furosemide (Lasix, Sanofi-Aventis), 
hydrochlorothiazide, and ranitidine (Zantac, GlaxoSmithKline), an antireflux 
drug, that have weaker anticholinergic properties, Dr. Tsao said. 
"When we actually looked through the literature, a lot of medicines that are 
not advertised as anticholinergic in nature actually have anticholinergic 
properties in vitro," he said. 
To look more closely at this potential problem in a wider population, they 
used data from the Rush Religious Orders Study, a longitudinal cohort study 
enrolling older Catholic nuns and clergy without known dementia at 
enrollment. Of these, 870 had at least 1 follow-up evaluation. 
During baseline and annual clinical evaluations, medication and supplement use 
was determined by direct observation of pill bottles, and global cognitive 
function was measured using a 21-item neuropsychological battery.
They divided subjects into those who had taken any of the drugs on the list 
they had compiled of those with anticholinergic properties (n = 679); 
subjects who had never taken any of these agents (n = 191) were used as the 
reference group. 
The subjects were observed for a mean of 7.8 person-years, the authors note. 
In piecewise-regression models adjusted for age, sex, and education, the 
level and annual rate of cognitive decline for individuals before and after 
starting an anticholinergic drug were compared with the intercept and slope 
for the reference group. 
Dr. Tsao and colleagues report that the level and annual rate of change were 
not significantly different between the medication and reference groups prior 
to the use of an anticholinergic agent. However, compared with the reference 
group, the rate of cognitive decline after anticholinergic use was 0.045 
units/year more rapid (P = .0044), the authors write. 
"As all subjects were cognitively normal at the time of entry into the 
Religious Order Study and none were taking medications with anticholinergic 
effects, we conclude that initiation of medications with anticholinergic 
activity is associated with a more rapid decline in cognitive performance," 
the authors conclude. 
In future work, they plan to stratify these agents on the basis of the 
relative potency of their anticholinergic effects to see whether more potent 
drugs may have a greater effect on memory compared with those that are less 
potent, Dr. Tsao concluded. "We're also going to try to see whether those 
subjects who might have mild cognitive impairment fare worse."
The study was supported by a grant from the American Philosophical Society and 
the National Institute on Aging. Dr. Tsao reports that he has received 
personal compensation for activities with CME LLC as an independent reviewer; 
holds stock and/or stock options in Amgen; and has received research support 
from Defense Spinal Cord and Column Injury Program, Uniformed Services 
University, and the Comprehensive Neuroscience Program. Disclosures for 
coauthors appear in the abstract.
American Academy of Neurology 60th Annual Meeting: Abstract S51.001. Presented 
April 17, 2008.

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