Cholinesterase Inhibitors and Neuropathology of Cerebrovascular Disease and Other Dementias in Patients with Alzheimer’s Disease: A Study of NACC Autopsy and Medical History Data, 2005 – 2017

In vitro testing of cholinesterase inhibitors suggested protective effects against neuronal toxicity from multiple sources. Investigations in primates found ChEI restored cerebral blood flow. Work in animals suggests ChEI may have a neuroprotective effect, though not necessarily impacting pathologies associated with Alzheimer’s Disease. Imaging studies had inconsistent results. Our objective was to assess the impact of ChEI on cerebrovascular or neurodegenerative pathologies in patients with AD. Using the National Alzheimer’s Coordinating Center database, we identified 2245 individuals with at least two annual visits where medications were recorded, an etiologic clinical diagnosis of AD, and who had died and completed neuropathological examination at autopsy. Generalized Estimating Equations were used to calculate the association between use of AD or cardiovascular medications and dementia pathology. Approximately 67% of the study population reported using a ChEI. Microinfarcts were negatively associated with rivastigmine (OR: 0.61; 95% CI: 0.37 – 0.99) and AD pathology was positively associated with use of donepezil (OR: 1.43; 95% CI: 1.04 – 1.96). Our findings suggest some value in further exploring the pathological impacts of ChEI.