333: Anticholinergic drug use, M1 receptor affinity and dementia risk- apharmacoepidemiological analysis using claims data

Background: Dementia is characterized by cumulative cognitive decline andprogressive inability for independent living. The lack of suitable therapies for terminatingthe progression of this disease underlines the importance of the detection of risk factors.Anticholinergic drugs have been shown to enhance cognitive decline in the elderly. Theclassification of anticholinergic drugs according to their anticholinergic burden, however,is inconsistent. Since cholinergic transmission is mainly mediated by the M1 muscarinicacetylcholine receptor in the brain, we classified anticholinergic drugs fromanticholinergic risk lists according to their affinity for the M1 receptor subtype andcalculated the risk for the onset of incident dementia.Methods: Our analyses are based on claims data of the public health insurance fundAOK. Data include information of inpatient and outpatient diagnoses and treatment from2004 to 2011. Inclusion criteria comprised the initial absence of dementia and age of 75years or older in 2004. Anticholinergic drugs were taken from three anticholinergic risklists. The PDSP-database and literature search were used to define Ki-values for thesubstances. Hazard ratios were calculated using time-dependent Cox regressionincluding covariates like age, gender, and several comorbidities.Results and Conclusion: Anticholinergic drug exposure increases the risk fordementia. We found that anticholinergics with small Ki-values are at a higher risk thanthose with greater Ki-values. Furthermore, conventional risk factors for dementia (e.g.age, depression, stroke) could be confirmed.In conclusion, the intake of anticholinergic drugs increases the risk for incident dementiain the elderly. Taking into account the M1 receptor affinity may be a contribution indetermining the anticholinergic load in view of the risk for incident dementia.