A Lack of Progress Towards Drugs that Improve Cognitive Function in Old Age

For many topics in aging for which there is presently little progress, it is nonetheless possible to find a great deal of relevant research and drug development undertaken over the past few decades. It is just that none of it managed to produce therapies, largely small molecule drugs given the primary focus of the research and development communities, that have a large enough effect to be interesting. This is the case for the improvement of cognitive function in old people. This review is a short tour through the highlights of past therapeutic development, and the summary at the end of the day is that nothing attempted to date can much improve on the effects of structured exercise programs. We can hope that this will change as more attention is given to targeting the underlying causes of aging, rather than the use of small molecules to manipulate specific protein interactions that are far downstream from those causes.

Aging is associated with cognitive impairment, including dementia and mild cognitive impairment (MCI). Successful drug development for improving or maintaining cognition in seniors is critically important. Although many novel targets are being explored for improving cognition in the past two decades, there are only several drugs approved to improve cognition in Alzheimer's disease (AD) and no drug has been approved for cognitive protection in MCI patients.

A growing number of studies show that non-pharmacological interventions can enhance cognition in the last decade. Emerging evidence indicates exercise not only promotes physical health but also contributes to the preservation of cognition function. The mechanisms account for the neuroprotective effects of exercise on the brain include evaluated neurotrophic factor levels, increased synaptogenesis, improved vascularization, decreased systemic inflammation, and reduced abnormal protein deposition.

Various pharmacological (cholinesterase inhibitors, memantine, antidiabetic agents, probiotics, cerebrolysin) and non-pharmacological interventions (cognition-oriented treatments, non-invasive brain stimulation, physical exercise, and lifestyle-related interventions) have been proposed for cognitive impairment in older people. Although a variety of new drug targets has been identified for cognition enhancement in older adults, these new drugs are still in development. The existing potential drug targets should be further exploited, and discovering new drug targets could be a solution to the lack of effective drugs. Most non-pharmacological interventions showed a small to moderate beneficial effect on cognitive function in cognitive impairment old people. Thus, combinations of pharmacological and non-pharmacological interventions or combinations of different types of non-pharmacological interventions may be more efficient in improving or preserving cognition.

Link: https://doi.org/10.3389/fnins.2022.1060556