Use of anticholinergic drugs
Of the 372 elderly people recruited from general practices in the south of France, 51 (14%, 95% confidence interval 10% to 17%) were taking at least one anticholinergic drug at the start of the study (42 taking one anticholinergic drug and nine taking more than one). None was taking acetylcholinesterase inhibitors. At one-year follow-up, 30 of these 51 participants were still taking anticholinergic drugs regularly, 26 taking the same drug. Twenty one participants had stopped taking anticholinergic drugs during the year, while 24 had started taking them. The following analyses thus concerned the 297 participants who had taken no anticholinergic drugs at baseline or in the following year and the 30 (9%, 6% to 12%) who had used anticholinergic drugs throughout the year. lists the drugs used and their estimated anticholinergic burden.
List of anticholinergic drugs used by study participants. All drugs had an anticholinergic burden classification of 3 (see Methods for details) unless stated otherwise
The 30 consistent users of anticholinergic drugs were predominantly women (77%) and, compared with the 297 consistent non-users, were older (mean (SD) age 80.9 (8.0) v 74.8 (7.4) years, P < 0.001) and less likely to have had tertiary education (10% v 19%).
Assessment of cognitive performance
compares the cognitive performance of the consistent users of anticholinergic drugs with that of the consistent non-users. The drug users showed significantly poorer simple reaction time, attention, immediate and delayed visuospatial memory, narrative recall, verbal fluency, and, to a lesser extent, object naming and visuospatial construction. A difference in immediate and delayed recall of names and name-face associations lost significance when adjusted for age, and the two groups showed no significant difference for implicit memory and logical reasoning.
Cognitive performance of consistent users of anticholinergic drugs and consistent non-users. Values are means (SD) test scores unless stated otherwise
Conversion of raw scores to z scores permitted direct comparison of performance across different tests. The shows the mean z scores for the two groups. While the non-users of anticholinergic drugs showed a relatively even performance across the tests, the users not only performed worse but showed considerable variability in their cognitive profile.
Mean z scores for 30 consistent users of anticholinergic drugs and 297 consistent non-users on tests of cognitive performance
A comparison of participants with a substantial anticholinergic burden (scoring 2 or 3 on our classification) with non-users of anticholinergic drugs showed that those with a burden score of 3 had poorer cognitive scores, but the differences between groups did not reach significance, possibly because of the small numbers of individuals.
Assessment of mild cognitive impairment
Among the 297 consistent non-users of anticholinergic drugs, mild cognitive impairment was diagnosed in 105 (35%, 95% confidence interval 30% to 41%). Among the 30 consistent users of anticholinergic drugs, however, 24 (80%, 66% to 94%) met the criteria for mild cognitive impairment, giving an attributable risk of 19%. To assess the extent to which a diagnosis of mild cognitive impairment was due to anticholinergic drug use, we created a logistic regression model to predict such a diagnosis at one-year follow-up, taking into account anticholinergic drug use over the previous year and other identified risk factors for cognitive impairment (age, sex, education, untreated depression, treated hypertension). After adjustment for other possible causes of cognitive impairment, the only highly significant predictors of mild cognitive impairment were anticholinergic drug use (odds ratio 5.12, 1.94 to 13.51; P = 0.001) and age (1.09, 1.06 to 1.13, P < 0.001). The other possible risk factors lost significance when age and anticholinergic drugs use were entered into the model.
Development of dementia
Although the consistent users of anticholinergic drugs were significantly more likely to have a diagnosis of mild cognitive impairment at one-year follow-up (80%) than consistent non-users (35%), we found no difference in overall dementia rates at eight-year follow-up between the drug users (16%) and non-users (14%). Small numbers of individuals made it impossible to make a statistical comparison of rates of conversion.