The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 2 • June 2015

FDA Approved Anticholinergic Drugs Prescribed for “Overactive Bladder” May Increase the Risk of Dementia and Alzheimer’s Disease

We have found additional reports in the literature, as far back as 2003,1,2 that warn of increased Alzheimer pathology in anticholinergic (antimuscarinic) drugs prescribed to treat “overactive bladder” in the elderly. These drugs do not have black box warnings about these disastrous potential side effects.

Although mildly effective in treating motor symptoms in Parkinson’s disease, but more often prescribed in these patients for bladder dysfunction, the use of antimuscarinic drugs has been shown to be associated with impaired neuropsychiatric and cognitive function. Clinical evidence suggests that M1 mAChR [M1 muscarinic acetylcholinergic receptor] antagonism may account for these unwanted side effects, as M1 AChR antagonists such as benztropine, orphenadrine, and trihexyphenidyl (Artane®) have been shown to increase amyloid plaque and neurofibrillary tangle densities similar to that found with Alzheimer’s disease pathology.

A 2003 paper1 reported on the autopsy findings for 120 neuropathologically confirmed Parkinson’s disease (PD) cases. The PD cases were divided into three subgroups depending on how long they had been using anti­muscarinic drugs for movement or bladder control. “None” indicated no use of such drugs, short term use was less than 2 years, long term greater than 2 years. They also had two subgroups according to the use for 1–10 years of tricyclic antidepressants (also antimuscarinics).

As we indicated in the first part of this article (see it in the May 2015 Life Enhancement magazine), one way to test for anticholinergic effects is whether or not a drug causes dry mouth. Tricyclic antidepressants do that. Not all drugs that cause dry mouth, however, are anticholinergics, so if you do experience dry mouth, you will need to check a reference to find out whether what you are taking has anticholinergic effects.

The results1 showed that there were no differences in Alzheimer pathology between the short-term use or no use (“None”) of antimuscarinics. However, plaques were more than twofold higher in the group chronically treated long term with antimuscarinics, tangles were twofold higher in the long-term treated as compared to the group exposed to no antimuscarinics. In the group treated with tricyclic antidepressants, plaques and tangles were more than twofold higher in the treated as compared to the untreated group though this did not reach significance and the authors note that depression itself may promote Alzheimer pathology. The authors conclude that their data are consistent with the possibility that prolonged use of antimuscarinic drugs “accelerates beta amyloidosis and senile plaque formation in the aging brain in subjects with PD.”

The commentary2 that discussed the above paper mentioned several anticholinergic medications used in the treatment of movement disorders (trihexyphenidyl, benztropine), urinary incontinence (tolterodine, oxybutynin) and dizziness (meclizine). The commentary notes that “[a]bundant evidence now implicates amyloidogenesis as a critical event in AD pathogenesis.” The authors then refer to evidence that muscarinic cholinergic stimulation can reduce amyloid beta formation in vitro and in vivo in animal studies, thus suggesting the way that antimuscarinics could be deleterious in AD. “The significance of these findings for the millions of healthy elderly patients taking anticholinergic drugs remains to be clarified.” They suggest that physicians prescribe these drugs cautiously and with frequent review and assessment of their benefits. We think that a strong warning should be required. When using a drug to treat a non-life threatening condition (urinary bladder incontinence), the acceptable potential downside should certainly itself be non-life threatening. That does not appear to be the case with anticholinergics for the treatment of urinary incontinence and we ourselves would avoid them entirely for this purpose.


  1. Perry, Kilford, Lees, et al. Increased Alzheimer pathology in Parkinson’s disease related to antimuscarinic drugs. Ann Neurol. 54:235–8 (2003)
  2. Allan I. Levey, MD, PhD. Chronically made as a hatter: anticholinergics and Alzheimer’s disease pathology. Ann Neurol. 54(2):144–6 (2003).

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