Aging and Dementia

Aging is clearly associated with a decrease in cognitive functions. Older people progressively experience forgetfulness. This is especially frustrating when learning new things. Besides memory function, other cognitive domains are affected as well, including attention and executive function. Cognitive decline comes with aging, but in some cases the deterioration accelerates beyond normal aging. This can ultimately lead to dementias like Alzheimer’s disease. In these cases, we observe a progressive and irreversible loss of cognitive functions. Currently, the treatment options are very limited. Available treatments have transient and minor positive effects, and are accompanied by adverse side-effects.

Our department has a long-standing history in researching novel targets for the treatment of cognitive deficits associated with aging or dementia. We conduct basic research in animal models in which we try to find new therapeutic targets to improve memory performance. This work is based on the seminal studies of Nobel Prize winner Prof. Eric Kandel. From these studies, it became clear that enhancement of neuronal function is not always best achieved through receptor activation. Instead, targeting intracellular signaling cascades might provide a more optimal target to modulate memory function. We use several pharmacological neurotherapeutics to stimulate or inhibit targets along the cyclic nucleotide signaling cascades. We modulate the spatiotemporal dynamics of these cascades either up- or downstream of cyclic nucleotides. For example, we are conducting studies using the phosphodiesterase type 4 (PDE4) inhibitor roflumilast as neurotherapeutic to enhance neuroplasticity and improve memory performance in human participants. After validating the concept in animal studies, we have shown in clinical studies that roflumilast can improve memory performance in humans.

The Memory Function of Sleep

Sleep loss is a common hallmark of modern society, which affects people of all ages and has a severe impact on body and brain. Even a brief period of sleep deprivation can result in cognitive deficits, particularly in the case of hippocampus-dependent memories. Several misregulated signaling mechanisms have been identified that may contribute to these cognitive impairments. The formation of memories requires consolidation processes both during the day and during the night. When we sleep, memories undergo both systems and synaptic consolidation. These processes are suggested to be linked to slow-wave sleep (SWS) and rapid eye movement (REM) sleep, respectively. The exact contribution of each stage to the formation of persistent memories is subject of debate and topic of active investigation within our department.

Despite that the molecular pathways responsible for how sleep loss causes memory loss are known at least to some extent, the question remains whether lack of sleep causes the full loss of information storage or whether the memory trace is merely too weak to be naturally retrieved. Both result in a memory deficit, however the latter provides opportunity for therapeutic intervention. In fact, our combined optogenetic and pharmacological studies have provided first evidence for the hypothesis that information remains in the brain and can thus, be it artificially, retrieved. These findings are currently being translated to human studies by following the Research Domain Criteria (RDoC) principles and using clinically-applicable substitutes for optogenetic reactivation of memory engrams.

Smart Pills

Everyone would like to have better memory. We always forget things when we need to remember something. When we get older, we tend to forget more. What can we do to improve our memory performance? On the internet you can find many solutions to improve your memory.

For example, there are hundreds different pills you can buy that will boost your performance. Just Google ‘pills memory’ and you will find things like Brain Smart, Braineffect, Focus, Sharp Mind etc. There are some nice quotes from people who buy these pills: ‘I finally get my work done’, ‘I can focus much more on my work’, and similar kinds of remarks. Many of these pills contain different ingredients like caffeine, ginkgo biloba extract, tyrosine, L-theanine. All these ingredients have shown some beneficial effects in experimental studies. Recently, we conducted a study in which we compared the cognition-enhancing effects of one of these so-called smart drugs with just caffeine or placebo. Although caffeine had a positive effect on cognition (better than placebo), the smart drug that contained different ingredients (including caffeine) had no effect. So, drinking coffee may be sufficient to boost your cognitive performance. Moreover, it’s cheaper!

Clearly, more studies are needed to test whether these smart drugs have a positive effect on cognition. The effects that people report on the website could easily be related to a placebo effect. Interestingly, the placebo effect in cognitive functions is not well investigated. Currently, we are planning studies in which we would like to examine how big this effect is and which factors lead to this placebo effect.