Obesity and cognitive dementia are among the most serious threats to human health and well-being. Both disorders have received an enormous amount of research attention, yet their root causes remain to be elucidated. Furthermore, short of artificially imposing severe restrictions on food intake by surgically remodeling the gastrointestinal tract, there appear to be no proven effective therapies that produce sustained weight loss in people. Similarly, effective interventions that prevent, reduce, or reverse the debilitating effects of AD-like dementias and other severe forms of cognitive decline are not yet available. The goal of research in the LBNH is to address these gaps in knowledge.
Our work is based on a novel theoretical conceptualization which suggests that both obesity and cognitive dementia may arise from common dietary origins and brain pathologies. These pathologies result in a progressive deterioration of the ability to engage cognitive processes that contribute to the inhibitory control of intake. Interference with these processes, which appear to involve the hippocampus and its connections to other brain regions, can promote overeating of the same type of dietary factors that produced the pathologies. Our theoretical model describes how this can lead to a " vicious cycle" of excess intake, obesity, and progressive cognitive decline, which could begin early in life and which could extend to failures in other forms of cognitive and memory functioning. By increasing understanding of how energy dysregulation and cognitive dysfunction may be interrelated in human and nonhuman animals, our research promises to yield new interventions that may more effectively treat or prevent both disorders.
Research with our collaborators at American University and at other universities is also beginning to examine the implications of our empirical findings and theoretical framework in two important domains. One goal is to identify and describe the relationships among diet, obesity, and cognitive functioning in school-age children. Similar to the population at large, the incidence of obesity has doubled in children ages 6-11 and has tripled in adolescents ages 12-19 since 1980. Although the most obvious and debilitating symptoms of cognitive dementias are manifested in old-age, there is evidence that brain pathologies underlying these disorders can begin at least 50 years earlier. Consistent with these reports are recent findings which link obesity to cognitive deficits that are revealed in childhood and that can continue to develop across the lifespan. Thus, while obesity is becoming widely recognized as a serious threat to the current and future physical health of our children, the threat posed by obesity to our children's cognitive health will also receive our research attention.
In addition, we are also beginning to extend our conceptual framework to the problem of drug abuse and addiction. There are many behavioral and physiological parallels between excessive drug and food intake. It appears that the set of brain pathologies and cognitive/memory deficits that we have shown to be associated with overeating are also involved with drug abuse. We aim to explore these apparent interrelationships with the goals of advancing knowledge about the mechanisms that cause addictive behaviors (i.e., both drug and food "addictions") and to identify important new targets for therapeutic interventions.
Join the Lab
Undergraduate students have the opportunity to learn about and participate in research on the inter-relationships among three pernicious and widespread threats to human health and well-being. Studying both rodents and humans, we explore the shared neural, hormonal, and cognitive processes that underlie obesity and addiction, and we investigate how both disorders can accelerate age-related cognitive decline, potentially culminating in dementia. Our work has shown that unhealthy diets and drugs of abuse can weaken the defenses of the hippocampus, a brain structure critical to important memory functions, to a variety of insults. Our current goal is to identify interventions that can protect the hippocampus from diet- and drug-induced damage.
Members of our research team will get hands-on experience conducting behavioral studies that evaluate the effects of dietary, hormonal, and pharmaceutical manipulations on hippocampal-dependent memory functions. Students will also take part in weekly lab meetings to discuss data we collect and weekly reading meetings where new findings from other laboratories are considered. Many students will also have the opportunity to co-author professional research papers or to present their findings at regional and national research conferences. Laboratory staff will provide students with all training needed to a participate in a research project. Although there are limited number of openings, beginning, as well as advanced, undergraduate students, who are conscientious, dedicated, and responsible, are welcome join our laboratory group.
Contact Dr. Terry Davidson:
On learning predictive relationships between sweet tastes and calories:
"It is likely that one of the earliest associations formed by humans and other animals is that based on the signaling relationship between sweet taste in the mouth and the subsequent arrival and absorption of calories in the gut. This type of signaling relationship is thought to enable sweet taste to evoke physiological responses that anticipate and promote the efficient utilization of the energy contained in foods and fluids. Therefore, if consuming non-caloric sweeteners weakens this relationship, the ability to regulate intake of sweet, high calorie foods and beverages could also be degraded (from Davidson, Martin, Clark, & Swithers, 2011).
Why do we eat or why can't we refrain from eating?
"When food and stimuli associated with food are encountered, these cues may evoke vigorous appetitive and consummatory responding on some occasions and little or no responding at other times. A common interpretation of this pattern of behavior is that animals engage in appetitive and eating behavior until they become satiated and then refrain from making these responses until satiety wanes. How does satiety inhibit, and the absence of satiety promote, appetitive responding? The answer to this question may depend on an animal's ability to resolve a predictable ambiguity by learning that satiety signals predict when food cues will not be followed by an appetitive postingestive outcome" (Davidson, Kanoski, Schier, Clegg, & Benoit, 2007).
On the role of motivational concepts in theories of feeding behavior.
"While our analysis refers to terms such as "sweet taste," "satiety signals," and "appetitive" and "aversive postingestive consequences,"we used these terms descriptively: not as explanations of behavior in their own right. That is, in our model sweet taste refers to a sensory rather than a hedonic property of food; satiety signals refer to sensory events of internal origin that suppress behavior, without ascribing that suppressive effect to any motivational property of satiety itself; appetitive and aversive consequences refer to outcomes of intake that promote or suppress, respectively, behavior that is instrumental to obtaining and consuming food, without the additional claims that those outcomes incentivize or reward the behaviors that are associated with them" (From Davidson, Sample, & Swithers, 2013).
Linking western diet consumption to obesity and cognitive disorders:
"It may be that the ability of a Western diet to interfere with hippocampal-dependent learning and memory processes is causally linked to its capacity to promote excessive energy intake and obesity. Research from our laboratory and elsewhere has shown that Western diet-induced learning and memory impairments can precede the development of diet-induced obesity. It may be the case that impairments in hippocampal-dependent processes promote intake and body weight gain by interfering with learned control of energy regulation" (from Kanoski & Davidson, 2011).
On potential links between obesity and Alzheimer's Disease (AD):
"Obesity and Alzheimer's Disease are two of the most serious health challenges facing Western cultures. At present, there are no effective therapies for either disease. Although most clinicians and scientists view these disorders as having distinct etiologies and underlying pathologies, the present findings suggest that both may have common dietary origins and brain substrates. Our results join with other recent findings in pointing to the need for a more integrative research approach that could help describe shared neuronal and behavioral mechanisms that may underlie obesity and AD and help identify effective new treatments to prevent or ameliorate both of these serious threats to well-being". (Kanoski, Zhang, Zheng, & Davidson, 2010).
On early-life cognitive deficits and late-life cognitive dementias:
"The results of human studies suggest that obesity is associated with cognitive decline across the lifespan, from relatively mild deficiencies early in life to severe dementia in old age Furthermore, the hippocampus and structures comprising the larger hippocampal formation have been identified as early targets of brain pathologies that give rise to progressive deterioration of cognitive function as such pathologies spread to additional medial temporal lobe structures and then to other areas of the brain. It may be that consuming diets high in saturated fat and carbohydrate produces changes in the brain that impair hippocampal-dependent cognitive functioning; these changes precede and perhaps contribute to overeating, leading not only to obesity and metabolic disease, but also to further interference with the hippocampus and perhaps other substrates for cognitive functioning. From this perspective, early detection of mild forms of hippocampal-dependent cognitive dysfunction and early therapeutic interventions that effectively treat these forms of cognitive disorder should also help to prevent subsequent weight gain and stop the initiation of a vicious-cycle of obesity and cognitive decline" (From Davidson, Hargrave, Swithers, Sample, Fu, Kinzig, & Zheng, 2013).