Adverse Effects of Anticholinergic Drugs on Cognition and Mobility: Cutoff for Impairment in a Cross-Sectional Study in Young–Old and Old–Old Adults
Drugs with anticholinergic properties are commonly prescribed in older adults despite growing evidence of their adverse outcomes. Several issues regarding these detrimental effects remain unresolved, such as the putative existence of a threshold above which anticholinergic drug consumption impairs cognitive or mobility performance.
We aimed to investigate the number of anticholinergic drugs and the anticholinergic burden that leads to mobility or cognitive impairment and compare the effects in community-dwelling older adults in two age groups (“young–old” 55–74 vs. “old–old” ≥ 75 years).
In a cross-sectional study, we identified drugs with anticholinergic (antimuscarinic) properties using the Anticholinergic Drug Scale. Cognition was assessed using the Mini Mental State Examination (MMSE) and the Trail Making Test (TMT-A and TMT-B), and mobility was assessed using the Timed Up and Go (TUG) test.
The study population consisted of 177 volunteers, 114 of whom were classed as young–old and 63 were classed as old–old adults. Despite the lack of cutoff values for impaired outcomes in young-old adults, impaired MMSE were significantly more numerous in users than in nonusers of anticholinergic drugs. In old–old adults, receiver operating characteristic (ROC) curve analysis indicated that taking a single anticholinergic drug per day was associated with impaired TMT-B completion time, TMT difference score (B–A), and TUG scores. The cutoff for anticholinergic burden was also one for these same outcomes. Based on these cutoff values, multivariate logistic regressions in old–old adults showed that the increased risk of impaired cognition and mobility was independent of confounding factors, including comorbidities. They also suggested that anticholinergic drugs would affect mobility through executive functions.
Drugs with anticholinergic (antimuscarinic) properties are associated with cognitive impairment in individuals as young as 55 years, and only one such drug per day, regardless of its anticholinergic burden, is associated with both impaired cognition and impaired mobility in old–old adults. Therefore, wherever possible, clinicians should avoid prescribing drugs with anticholinergic properties.
The authors thank Drs. Valérie Caridroit, Thiphaine Ciappucini, Murielle Michel, and Pascale Lescure for their participation in the medical examinations, Kristell Pothier for her significant contribution to the experimental part, Anita Jamet for her contribution to the recruitment of participants, and Valérie Constans for English proofreading.
Compliance with Ethical Standards
This work was supported by the French Ministry of Health (PHRC Programme Hospitalier de Recherche Clinique 2011 no. 2011-A00534-37), and E. Attoh-Mensah was supported by the Togolese Ministry of Higher Education and Research (No. 525/MESR/SG/DBS) and the Normandy Association for Physiology Research (ANDREP).
Conflict of interest
EA-M, GL, PS-B, RM, PD, CM, and CC have no conflicts of interest that are directly relevant to the content of this article.
The Lower Normandy Ethics Committee approved this study (no. 2011-A00534-37; clinical trial registration number: NCT02292316).
Each participant signed and provided written informed consent.
- 2.Dauphinot V, Mouchoux C, Veillard S, Delphin-Combe F, Krolak-Salmon P. Anticholinergic drugs and functional, cognitive impairment and behavioral disturbances in patients from a memory clinic with subjective cognitive decline or neurocognitive disorders. Alzheimers Res Ther. 2017;9(1):58.CrossRefGoogle Scholar
- 5.de Germay S, Lapeyre-Mestre M, Montastruc J-L, Montastruc F. Atropinic burden and anticholinergic drugs: interest and application in clinical practice in the elderly. Therapie. 2018.Google Scholar
- 6.Andre L, Gallini A, Montastruc F, et al. Anticholinergic exposure and cognitive decline in older adults: effect of anticholinergic exposure definitions in a 3-year analysis of the Multidomain Alzheimer Preventive Trial (MAPT) study. Br J Clin Pharmacol. 2018.Google Scholar
- 16.Chuang Y-F, Elango P, Gonzalez CE, Thambisetty M. Midlife anticholinergic drug use, risk of Alzheimer’s disease, and brain atrophy in community-dwelling older adults. Alzheimers Dement (N Y). 2017;3(3):471–9.Google Scholar
- 29.de Groot V, Beckerman H, Lankhorst GJ, Bouter LM. How to measure comorbidity. A critical review of available methods. J Clin Epidemiol. 2003;56(3):221–229.Google Scholar
- 32.Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–198.Google Scholar
- 38.Kalafat M, Hugonot-Diener L, Poitrenaud J. The Mini Mental State (MMS): French standardization and normative data [Standardisation et étalonnage français du “Mini Mental State” (MMS) version GRÉCO]. Revue de Neuropsychologie. 2003;13:209–36.Google Scholar
- 44.Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev. 2012;(9):CD007146.Google Scholar