Translational Identification of Medication Repurposing Candidates to Slow Cognitive Decline in Dementia

Dementia creates a great personal and societal burden and there are currently no treatments to stop memory loss. Many patients with dementia take medications to treat other conditions, e.g. high blood pressure and cholesterol. Some of these medications may have central effects on the pathophysiological processes leading to dementia.

Medication repurposing is a cost and time-effective way to discover new treatments. Swedish registers are a unique tool to detect medication candidates for repurposing. The Swedish Dementia Registry (SveDem) has >100000 patients and ca. 144000 measures of cognition over time (measured with the Mini-Mental State Examination-MMSE), making it perfect to examine whether certain medications are associated with less cognitive decline in patients with dementia. Cholesterol and kidney function affect treatment and cognition and are available for 25000 patients. The investigators propose a study combining traditional cohort studies and newer artificial intelligence (machine learning) techniques to detect medications associated with slower cognitive decline in patients from SveDem. The investigators will test pre-specified hypotheses since the investigators suspect specific medications are better candidates to prevent cognitive decline, but the investigators will also let the machine learning algorithms explore the data to find associations that the investigators do not suspect in advance. Finally, the candidate medications will be tested in animal and cellular models to determine the mechanisms of their effects.