Use of some anticholinergic drugs increases risk of dementia
Some classes of anticholinergic drugs (antidepressants, antiparkinsons and urologicals) are strongly associated with the risk of a diagnosis of dementia up to 20 years after exposure, according to a recent study. On the other hand, other anticholinergics do not appear to be linked to dementia risk, and risks for other drugs remain uncertain.
“This could be caused by a class-specific effect or by drugs being used for very early symptoms of dementia,” researchers said.
“Clinicians should continue to be vigilant with respect to the use of anticholinergic drugs and should consider the risk of long-term cognitive effects, as well as short-term effects, associated with specific drug classes when performing their risk-benefit analysis,” they added.
A total of 14,453 (35 percent) patients and 86,403 (30 percent) controls received a prescription of at least one anticholinergic drug with an Anticholinergic Cognitive Burden (ACB) score of 3 (definite anticholinergic activity) during the exposure period. Any anticholinergic drug with an ACB score of 3 had an adjusted odds ratio of 1.11 (95 percent CI, 1.08–1.14). [BMJ 2018;361:k1315]
There was an association between dementia and an increasing average of ACB score. Consideration by drug class showed that gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia.
Furthermore, greater exposure to antidepressant, urological and antiparkinson drugs with an ACB score of 3 increased the risk of dementia, and this finding was also observed for exposure 15–20 years prior to a diagnosis.
“Possible explanations for our findings are that other actions of specific groups of anticholinergic drugs may underlie observed effects, or that the drugs are markers of prodromal symptoms or dementia risk factors,” researchers said. “Alternatively, the class-specific association we have observed may reflect a difference in the ability of different groups of anticholinergics to cross the blood-brain barrier.”
There is limited mechanistic evidence linking anticholinergic drugs with dementia incidence, but neuropathological studies in humans and mice indicate that anticholinergics may have a role in neurodegenerative pathology. [Neurodegener Dis 2015;15:140-148; Ann Neurol 2003;54:235-238]
Moreover, a recent cross-sectional analysis of Alzheimer’s Disease Neuroimaging Initiative and Indiana Memory and Ageing Study data associated anticholinergic drug use with reduced glucose metabolism and increased brain atrophy, as well as with future mild cognitive impairment or Alzheimer’s disease incidence among cognitively normal participants. However, this study did not disaggregate drug subclasses, according to researchers. [JAMA Neurol 2016;73:721-732]
“Evidence from anticholinergic cessation trials have not shown improvement in cognitive function, but these have been underpowered and focused on short-term outcomes,” they added. [Int J Clin Pract 2008;62:1792-1800]
The present case-control study included 40,770 patients aged 65–99 years with a dementia diagnosis between April 2006 and July 2015, and 283,933 controls without dementia. Interventions involved daily defined doses of anticholinergic drugs coded using the ACB scale, in total and grouped by subclass, prescribed 4–20 years before a diagnosis of dementia.
“Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure,” researchers said.