PhD defence A. Alghamdi

Medication use and cognitive outcomes in older adults

Investigating drug repurposing potential for Alzheimer’s disease prevention

This thesis investigated whether existing medications could be repurposed to help prevent or delay Alzheimer’s disease (AD), the most common form of dementia worldwide. Because current Alzheimer’s treatments only relieve symptoms and do not stop disease progression, there is an urgent need for new preventive strategies. Developing entirely new drugs is costly and time-consuming, so this research focused on “drug repurposing,” which means finding new uses for already approved medicines.

The research used large healthcare databases in the Netherlands, including the IADB.nl prescription database and the Lifelines population cohort. Several medication groups were studied, including cardiovascular drugs, respiratory drugs, and antiviral medications. The thesis also examined patterns of polypharmacy, defined as the use of multiple medications, in older adults before an Alzheimer’s diagnosis.

The findings showed that people later diagnosed with Alzheimer’s disease used more medications overall and were more frequently exposed to drugs that may negatively affect cognition. Studies on beta-blockers and beta-agonists showed mixed and inconclusive results regarding cognitive protection. However, the strongest findings involved antiherpetic drugs such as valacyclovir, acyclovir, and famciclovir. These medications were consistently associated with a lower risk of later Alzheimer’s treatment initiation. Evidence from herpes zoster vaccination studies also suggested a reduced risk of dementia. Overall, the thesis supports the idea that some existing medications, particularly antiviral therapies, may have potential in Alzheimer’s disease prevention and deserve further clinical investigation.

Supervisors:prof. dr. E. (Eelko) Hak, prof. dr. B.C. (Barbara) van Munster