A new study published in BMC from a leading Parisian memory clinic has raised concerns about the safety of widely prescribed medications in older adults with cognitive decline. The research suggests that anticholinergic drugs, commonly used to treat urinary incontinence, depression, and allergies, may significantly increase the risk of death, particularly among individuals showing biological signs of Alzheimer’s disease.
The analysis included 927 patients aged 65 and older who had been diagnosed with either mild or major neurocognitive disorders. Each participant underwent cerebrospinal fluid testing to measure three key Alzheimer’s-related biomarkers namely amyloid, phosphorylated tau, and total tau. Based on these results, patients were classified into amyloid tau neurodegeneration profiles, a framework used to stage Alzheimer’s and related neurodegenerative conditions.
Anticholinergic medications interfere with the brain’s cholinergic system by blocking acetylcholine, a neurotransmitter essential for memory and cognition. These drugs act on muscarinic and nicotinic receptors and have long been associated with adverse cognitive effects.
To assess drug exposure, researchers applied the Anticholinergic Cognitive Burden scale, which ranks medications by their impact on brain function. Patients were grouped into three categories: no burden with a score of zero, low to moderate burden with a score of one to two, and high burden with a score of three or more. Results showed that individuals with high anticholinergic burden had a 30% higher risk of death compared to those with no burden. However, this association weakened after adjusting for age, sex, clinical status, and genetics.
Abnormal ATN biomarker profiles continued to strongly predict mortality risk. When high anticholinergic exposure was combined with Alzheimer’s-like biomarker patterns, particularly the A + T + Nx profile which reflects amyloid positivity, tau positivity, and neurodegeneration positivity along with additional biomarker abnormalities, the risk of death more than doubled. This suggests a potential synergistic effect between drug burden and underlying disease pathology.
These results are consistent with earlier findings by Weigand and colleagues, who reported that anticholinergic exposure increased the likelihood of mild cognitive impairment and cognitive decline, especially in individuals carrying genetic risks or Alzheimer’s biomarkers.
The study highlights the urgent need for a more personalized approach to dementia care. By integrating pharmacological risks with biological markers, clinicians may be able to better predict outcomes and tailor treatments. Reducing unnecessary exposure to anticholinergic drugs could serve as a relatively simple yet effective strategy to lower mortality in vulnerable patients.
As the global population ages and Alzheimer’s diagnoses rise, the findings underscore the critical need for cautious prescribing of medications. For older adults with cognitive decline, balancing treatment benefits with long-term safety is crucial. Clinicians are urged to review prescriptions carefully, minimize unnecessary anticholinergic use, and consider safer alternatives. Aligning treatments with biological risk factors could help improve survival and quality of life in this vulnerable population.
References
- Decaix, T., Dumurgier, J., Cognat, E. et al. Dual risk of anticholinergic burden and CSF Alzheimer’s biomarkers in older patients: a mortality follow-up study from daily medical practice. Alz Res Therapy 17, 162 (2025).
- Ghossein N, Kang M, Lakhkar AD. Anticholinergic Medications. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Sept 15]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK555893/
- eigand AJ, Bondi MW, Thomas KR, Campbell NL, Galasko DR, Salmon DP, Sewell D, Brewer JB, Feldman HH, Delano-Wood L; Alzheimer’s Disease Neuroimaging Initiative. Association of anticholinergic medications and AD biomarkers with incidence of MCI among cognitively normal older adults. Neurology. 2020 Oct 20;95(16):e2295-e2304.