Many drugs have anticholinergic effects, which may be their main therapeutic action, or an additional effect. Anticholinergic drugs block the activity of the neurotransmitter acetylcholine (ACh). ACh slows the heart rate, induces vasodilation, constricts the pupils, and triggers bladder contraction and intestinal motility.₁ In the central nervous system, ACh is involved in memory, learning and cognition, motor regulation, reward and arousal. Dementia and Parkinson’s disease are both linked to abnormalities in cholinergic pathways in the brain.₁ 

Anticholinergic drugs are used to manage hay fever, motion sickness, COPD, depression, psychosis, and overactive bladder. Between 27 and 51 per cent of older adults take medications with anticholinergic effects._2,3 However, these drugs have a long list of potential adverse effects to which older adults are especially vulnerable, including constipation, urinary retention, hypotension, blurred vision, sedation, confusion, reduced cognition, and delirium. All these increase the risk of falls.₁ 

Anticholinergic drugs can be classified by their impact on the ageing brain. One tool is the Anticholinergic Cognitive Burden (ACB) scale which includes four categories:_3,6 

0. No anticholinergic action.
1. Possible anticholinergic effects e.g. beta-blockers, ACE inhibitors, digoxin, warfarin, opioids, thiazide & loop diuretics, some antihistamines.
2. Moderate anticholinergic effects e.g. many phenothiazines (antipsychotics), amantadine (for Parkinson’s), cimetidine, carbamazepine, scopolamine, loratadine, loperamide.
3. Strong anticholinergic effects e.g. many atypical antipsychotics, tricyclic antidepressants such as amitriptyline, atropine, drugs treating overactive bladder (oxybutynin, solifenacin, tolterodine), and antiparkinson’s drugs such as procyclidine.

Increased mortality is seen with higher scores: every additional ACB point increases the risk of dying by 26 per cent.₄ It is possible to have a high score through use of multiple ACB-1 drugs only.₆

But now there is research from the UK directly linking some anticholinergics to the development of dementia. The case-controlled study—where differences in exposure to a risk factor (eg. anticholinergic drugs) are compared to development of an outcome (eg. dementia)— showed an 11 per cent increase in the risk of dementia for people taking at least one ACB-3 anticholinergic.₅ Greatest risk was with drugs for Parkinson’s, overactive bladder and depression. ACB-1 anticholinergics did not increase risk and nor did class 3 gastrointestinal drugs, antipsychotics or antihistamines.₅ 

While this study shows an association between the drugs and dementia, it does not explain causation. Further, the data were from a prescribing database which cannot reveal over-the-counter drug use or treatment adherence.₅ The increase in risk is small: ten out of 100 people aged 65 to 70 in the UK develop dementia over 15 years but with exposure to these drugs only an extra 2 cases will occur.₅ It is important to consider risk versus benefit for any drug and any patient, but especially older adults who are already at risk of impaired cognition. Any reduction in the burden of anticholinergic drugs without adversely affecting health should be considered.

References

1. Rang, H. et al., (2016). Rang and Dale’s Pharmacology. (8^th ed.). London: Churchill Livingstone/Elsevier.
2. Gray, S. & Hanlon, J. (2018). Anticholinergic drugs and dementia in older adults. BMJ. 361:k1722.
3. Maples, J. et al. (2015). Concordance between anticholinergic burden scales. Journal of the American Geriatrics Society. 63(10): 2120-2124.
4. Fox, C. et al. (2011). 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. 59(8): 1477-1483.
5. Richardson, K. et al. (2018). Anticholinergic drugs and risk of dementia: case-control study. BMJ. 361:k1315 
6. Parkinson, L. et al. (2015). Anticholinergic burden in older women: not seeing the wood for the trees? Medical Journal of Australia. 2010(2): 91-94.
7. Anticholinergic burden. The ACB Calculator. http://www.acbcalc.com/pages/about