Can we get smarter and remember better and how?
I have placed (labeled) this post as belonging in the neuromechanics box because developing a cognitive enhancing drug should logically be based on detailed knowledge of how cognitive functions like learning or memory work. Unfortunately we have only a fuzzy sketch of the neural basis of how we think, learn, and remember which limits our ability to develop a cognitive enhancer. This should not stop us from wishing or talking about it. However given our weak knowledge base that defines the neurobiology of cognition claims of the discovery of cognitive enhancing agents should trigger not just surprise and excitement but loads of skepticism.
How might a cognitive enhancing drug work? For that matter we might also ask what do we mean by a behavioral treatment that can improve cognition. An agent might act directly on the components of the brain circuitry that is the basis of some cognitive operations such as memory or attention (this would be called a mediation effect). For example a drug that improves the functioning of neurotransmitters that are involved in memory might be a candidate for treating memory problems in patients with Alzheimer’s disease or age related memory loss. Some agents might act to stimulate cognition via and indirect route (a modulatory effect). That is the mode of action effects some aspect of our behavior such as how aroused or awake we are and this has a secondarily effect on cognition. For example, if someone is performing their job while being very sleepy treating them with a stimulant may make someone more alert and therefore more cognitively effective since being sleepy impairs learning, memory or attention. In considering what may be a cognitive enhancer one should also ask whether the agent of change is designed to reverse a deficit as in a clinical condition or a deficit state of mind in contrast to improving cognitive functions in normal individuals (i.e., inducing super cognitive performance).
You should realize that cognitive enhancers have been around for well over 50 years. During World War II bomber pilots flying long missions used stimulants such as amphetamine to remain more alert and to function more effectively (a modulatory effect in normals). Other examples of modulatory cognitive drug effects may account for how Adderall and Ritalin act to treat mental functions in Attention deficit/Hyperactivity Disorder. The positive effects of these ‘stimulants’ are not through boosting the efficiency of the attention system directly but rather by blunting impulsivity, distractibility, and restlessness. Cognitive impairments are common in depressed patients. An effective antidepressant will improve cognitive functioning when depressed symptoms subside. The cognitive effects are modulatory because they are secondary to effects on depression rather than on cognition directly.
Many avenues of research have been explored in the search for drugs that can improve cognitive functioning in patients with Alzheimer’s disease or in those with age-related cognitive decline. Most of this research is built on what we know about the pathophysiology of Alzheimer’s disease and brain changes associated with aging along with our understanding of the neurochemistry of memory. The focus of this research is to find drugs that target the mediators rather than the moderators of cognitive functions like memory. So far several drugs have been developed and tested in the clinic but with very modest effects. For example drugs, such as Tacrine, which target the memory relevant cholinergic nervous system, have been accepted as anti dementia drugs by the Food and Drug Administration. To date no strong viable candidate drugs have emerged but claims of effectiveness are nevertheless rampant.
There has been a sprinkling of reports of healthy normals self-reporting that stimulants such as Adderall along with a newer drug Provigil (catchy name) have positive effects on cognition. Few controlled studies have substantiated such claims. One report in a science journal did show that Provigil improved working memory in normal individuals but the size of that effect may be of the same order as large doses of caffeine.
The explosion of cognitive neuroscience research and knowledge will continue to fuel the search for cognitive enhancers. Trying to find ways to boost our mental functions and perhaps help patients along the way is an irresistible venture.
However, we are all suckers for scams and promises that we will become smarter, better looking, more successful and all we need is……..plus shipping and handling.