Novel and Emerging Treatments
Guanfacine is a drug approved by the Food and Drug Administration for treating attention deficit hyperactivity disorder (ADHD), and it has gained interest as a treatment for memory problems (Flight 2011). Guanfacine works by stimulating parts of the brain that respond to the hormone epinephrine (Decamp 2011). This drug was found to improve working memory and attention in animal models (Arnsten 1988; Decamp 2011; McAllister 2011). It has also been shown to improve working memory in humans (Jakala 1999; Swartz 2008). Although this drug has not yet been approved for the treatment of memory disorders in humans, its potential for helping to slow or reverse memory decline remains intriguing, especially as it has already been approved for use in other conditions (Flight 2011).
Piracetam is a synthetic derivative of the inhibitory neurotransmitter gamma-amino butyrate (GABA). There are several piracetam analogues, known as the “racetams,” and these compounds have been studied for their neurological and vascular effects in conditions ranging from ischemic stroke to Alzheimer’s disease since the 1960’s (ClinicalKey 2013). Piracetam has gained interest as researchers work to find treatments for memory problems (Waegemans 2002; Samartgis 2012). Although the exact mechanism by which piracetam works is not fully understood (Rao 2012), it appears to improve cell membrane fluidity (an important aspect of neuronal health), and modulate the flow of ions in and out of neurons (ions are integral components of neuronal signal transduction). Piracetam has been shown to reduce neuron damage associated with oxygen deprivation and reoxygenation in cell culture studies (Solanki 2011) and to improve memory and anxiety in animal models of amnesia (Grossman 2011; Samartgis 2012). Case reports also show that it may be useful in treating amnesia in humans, though there are some concerns in patients with psychiatric disease, as evidence suggests the possibility that piracetam could worsen conditions such as psychosis (Rao 2012). Although more studies are needed to determine if piracetam exerts a meaningful benefit in amnesia, its long history of safe use and its ability to modulate neuronal properties make it a candidate for future research in this area.
Applying electrical currents to the brain may also treat amnesia. Two different techniques for supplying these currents have been studied. The least invasive is transcranial direct current stimulation, which uses saline-soaked sponge electrodes applied to the surface of the head to deliver mild electrical currents (Hansen 2012). It appears that these mild electrical currents can modulate the way that neurons work (Zaehle 2011; Hansen 2012). Studies have found that transcranial direct current stimulation improves working memory and recognition memory (Ferrucci 2008; Ohn 2008; Tseng 2012; Zaehle 2011). Another method of delivering electrical currents is called deep brain stimulation, in which electrodes are surgically placed inside the brain to deliver mild electrical currents to specific brain regions. One of the first journal articles to describe this possibility was a case report of a man who was receiving deep brain stimulation as a treatment for obesity and, unexpectedly, noticed improved memory (Hamani 2008). Since then, scientists have performed a small study using deep brain stimulation on patients with epilepsy who did not respond to drugs, and have found that these currents could improve the formation of memories of spatial information (Cheng 2012; Suthana 2012).
Hormones and Hormone Replacement Therapy
Changes in hormone levels may also play a role in amnesia. A class of hormones called neurosteroids are synthesized within the nervous system and modulate several aspects of brain function. Two neurosteroids in particular have been implicated in memory disorders: pregnenolone and dehydroepiandrosterone (DHEA) (George 2010). In animals, increasing age has been associated with lower pregnenolone levels. Moreover, memory impairment was associated with low pregnenolone levels, and several animal models revealed that pregnenolone administration into the nervous system improved memory (Mayo 2001; Vallée 1997; Chen 2010; Petit 2011).
In addition to its direct effects on the brain, pregnenolone also serves as a precursor for DHEA. Much like pregnenolone, DHEA levels drop dramatically (by as much as 80%) in old age. This decrease in DHEA may play a role in the gradual decline of memory and cognitive function in the elderly as well as in patients with Alzheimer’s disease (Sorwell 2010). Animal studies found that DHEA supplementation improves memory (Bazin 2009; Ducharme 2010). Although human studies on the effects of DHEA are limited, DHEA also may improve memory in young healthy males (Alhaj 2006).
Other hormones, including estrogen, have also been found to play a role in preventing amnesia in animal models (Gibbs 2011; Durham 2012). In humans, verbal declarative memory was found to be increased in the postmenstrual period of the menstrual cycle, when estrogen levels are high as compared to in the premenstrual period, and verbal memory appears to improve after the administration of estrogens in women who surgically enter menopause (Protopopescu 2008; Henderson 2009). Estrogen supplementation is an especially intriguing target as estrogen has been found to increase the levels of a compound called brain-derived neurotrophic factor (BDNF), which increases the connections between neurons and aids in making memories (Sanchez 2006; Luine 2013).
Progesterone, another important hormone that has neurological functions, may be useful for treating amnesia. Like other neurosteroids, progesterone also affects the growth and development of neurons (Mannella 2012). In animal models, progesterone has been shown to affect the number of connections between nerve cells (Woolley 1993). Progesterone has also been found to reduce chemically induced amnesia in animal models (Tanabe 2004). In addition, post-menopausal women who receive early hormone replacement therapy, including progesterone, have more brain activity in the hippocampus (Smith 2011). Progesterone supplementation has also shown promise in improving the neurological function, and it improved the outcome in patients who suffered traumatic brain injury (Ma 2012; Wright 2007).
Individuals interested in learning more about the benefits of hormone restoration therapy and how to move forward with hormone supplementation are encouraged to review Life Extension’s Male Hormone Restoration or Female Hormone Restoration protocol.