Delia Bishara1, Gayan Perera2, Daniel Harwood3, David Taylor4, Justin Sauer4, Nicola Funnell3, Robert Stewart4, Christoph Mueller4. 1. King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom. Electronic address: delia.bishara@slam.nhs.uk. 2. King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom. 3. South London and Maudsley NHS Foundation Trust, London, United Kingdom. 4. King's College London, Institute of Psychiatry, Psychology and Neuroscience, London, United Kingdom; South London and Maudsley NHS Foundation Trust, London, United Kingdom.
Abstract
OBJECTIVES: To investigate the associations between central anticholinergic burden and mortality, hospitalization, and cognitive impairment in people with dementia prescribed anticholinergic drugs for urinary symptoms. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients diagnosed with dementia receiving anticholinergic medication for bladder conditions (N = 540), assembled from a large healthcare database. METHODS: Central anticholinergic burden related to bladder drugs was estimated using the anticholinergic effect on cognition scale. Data were linked to national mortality and hospitalization data sources, and serially recorded Mini-Mental State Examination scores were used to investigate cognitive decline. RESULTS: Patients had a median survival of 4.1 years. Urinary drugs with a high anticholinergic effect on cognition score (tolterodine, oxybutynin) were associated with a 55% increased mortality risk (hazard ratio 1.55; 95% confidence interval 1.19‒2.01; P = .001) compared with drugs with low or no central anticholinergic burden (darifenacin, fesoterodine, trospium, mirabegron, solifenacin). Cognitive decline over a 24-month period around diagnosis was only detectable in the high central anticholinergic group, but there was no significant difference in cognitive trajectories between the high and low/no anticholinergic bladder drug groups. No increase of emergency hospitalization risk was seen in relation to central anticholinergic burden. CONCLUSIONS AND IMPLICATIONS: Urinary drugs with high central anticholinergic burden cause more harm than those acting peripherally and should be avoided in people with dementia. Further research is needed to test whether centrally acting anticholinergic agents in general cause worse outcomes in dementia.
OBJECTIVES: To investigate the associations between central anticholinergic burden and mortality, hospitalization, and cognitive impairment in people with dementia prescribed anticholinergic drugs for urinary symptoms. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Patients diagnosed with dementia receiving anticholinergic medication for bladder conditions (N = 540), assembled from a large healthcare database. METHODS: Central anticholinergic burden related to bladder drugs was estimated using the anticholinergic effect on cognition scale. Data were linked to national mortality and hospitalization data sources, and serially recorded Mini-Mental State Examination scores were used to investigate cognitive decline. RESULTS: Patients had a median survival of 4.1 years. Urinary drugs with a high anticholinergic effect on cognition score (tolterodine, oxybutynin) were associated with a 55% increased mortality risk (hazard ratio 1.55; 95% confidence interval 1.19‒2.01; P = .001) compared with drugs with low or no central anticholinergic burden (darifenacin, fesoterodine, trospium, mirabegron, solifenacin). Cognitive decline over a 24-month period around diagnosis was only detectable in the high central anticholinergic group, but there was no significant difference in cognitive trajectories between the high and low/no anticholinergic bladder drug groups. No increase of emergency hospitalization risk was seen in relation to central anticholinergic burden. CONCLUSIONS AND IMPLICATIONS: Urinary drugs with high central anticholinergic burden cause more harm than those acting peripherally and should be avoided in people with dementia. Further research is needed to test whether centrally acting anticholinergic agents in general cause worse outcomes in dementia.
Authors: Shanna C Trenaman; Austin Harding; Susan K Bowles; Susan A Kirkland; Melissa K Andrew Journal: Front Pharmacol Date: 2022-06-22 Impact factor: 5.988