Markedly Increased Risk
Over a mean follow-up of 7.3 years, 23% of all of the subjects developed dementia, and 19% were considered to have possible or probable Alzheimer's. Of those who showed signs of dementia, 79% ultimately went on to be diagnosed with Alzheimer's.
The risk was clearly associated with exposure to anticholinergic drugs, and it correrlated strongly with cumulative dose.
Among people with the highest and longest exposure, the risk of Alzheimer's was 77% higher than those who never took anticholinergics during the study period. Exposure to these drugs was expressed in terms of Total Standardized Daily Dose (TSDD) of 1095 or greater, based on a reference level of 5 mg oxybutyin representing 1 TSDD (Gray SL, et al. JAMA Intern Med. 2015; 175(3): 401-407).
Taking an anticholinergic daily for the equivalent of three years or more was associated with a 54% higher dementia risk than taking the same dose for three months or less.