An increasing number of longitudinal cohort studies have identified a risk increase for dementia by the chronic use of drugs with anticholinergic properties. The respective data from the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe) also showing risk increase (hazard ratio = 2.081) are reported here. The mechanisms by which the risk increase is transported are still unknown. Irritation of compensated alterations of cholinergic transmission at the pre-dementia stage of Alzheimer's disease (AD) or acceleration of neuroinflammation by disturbance of the anti-inflammatory effect of cholinergic innervation are discussed. In terms of dementia prevention, centrally acting anticholinergic drugs should be strictly avoided, because of long-term dementia risk increase in addition to acute negative effects on cognition.