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Anticholinergic activity of medications may produce significant cognitive decline in Parkinson's disease.
In this issue, Ehrt et al (see page 160) report that patients with Parkinson's disease (PD) treated with a variety of medications with anticholinergic activity had a significantly greater cognitive decline than patients with PD never medicated with those drugs. This is the first longitudinal study to show a detrimental effect of drugs with anticholinergic activity in PD. The relevance of the findings is increased by the large sample included in the study, the fact that patients were recruited from a community based cohort, by the relatively long follow-up and the classification of anticholinergic activity based on a standardised method.
Cognitive deficits related to the use of anticholinergic drugs are a well known phenomenon in PD. Some studies showed that anticholinergic induced deficits specifically affect executive functions1 while studies with a short follow-up showed that anticholinergic drugs may be detrimental to short-term memory performance.2
Ehrt et al are to be commended for their clinically relevant study, which highlights the importance of checking all the medications administered to PD patients. Results, however, may also be interpreted in different but still interesting ways. The fact that 82% of the patients in the anticholinergic activity group were on antidepressants suggests a high frequency of depression in this group. Previous studies demonstrated a significant cognitive decline in depressed patients with major depression compared with non-depressed patients.3 Therefore, the presence of more severe psychopathology in the anticholinergic activity group may account (at least partially) for the cognitive decline. The drop in Mini-Mental State Examination scores in the anticholinergic activity group is rather large to be solely explained by anticholinergic activity, and the mean Mini-Mental State Examination score of 25 in the anticholinergic activity group suggests that this group may have included some patients with early dementia. One methodological limitation is that the duration of treatment with anticholinergic activity drugs was not provided, and whether some patients were on these drugs for a short period only could not be ascertained. It is not stated whether the no anticholinergic activity group were on psychoactive drugs without anticholinergic activity. If this group received less psychoactive treatment than the anticholinergic activity group, findings could be construed as showing that the use of psychoactive compounds (regardless of their anticholinergic activity) are related to a faster cognitive decline. Clarifying these issues will help to unravel an important ethical dilemma, given that a recent study demonstrated the efficacy of the tricyclic nortriptyline (with known anticholinergic activity) to treat depression in PD.4
In conclusion, Ehrt et al demonstrated for the first time a significant association between a higher use of drugs with anticholinergic activity and cognitive decline in PD. Whether this decline is fully accounted for by anticholinergic activity, the use of psychoactive medication or by increased psychopathology will require further studies.
Competing interests None.
Provenance and peer review Commissioned; not externally peer reviewed.
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