Neurodegenerative diseases that degrade regions of the brain will eventually become

Maren Johnson CD 730 Research Paper What is the underlying neurological explanation for overeating in Frontotemporal Dementia? Does the change in overeating affect swallowing? Neurodegenerative diseases that degrade regions of the brain will eventually become salient enough to cause behavioral changes that can be observed in people. In diseases such as Frontotemporal dementia, a neurodegenerative disease noted by atrophy in the frontal and temporal lobes, can cause striking and varied behavioral changes. These changes in behavior can encompass a large variety of categories that distinguish it from other neurodegenerative diseases. Behavioral features that were noted to differ from others include: loss of insight, disinhibition, apathy, mood changes, stereotypic behavior, and abnormal eating behavior (Bozeat et al., 2000). Although many of these features are also seen in neurodegenerative diseases, the heterogeneity of symptoms of Frontotemporal dementia make it different in its presentation. One factor in particular that stands out is overeating. One of the more striking and salient characteristics in the pathology of this disease is the changes in eating behavior. Researchers noticed changes in eating patterns by examining the results of caregiver surveys that covered a range of areas. The characteristic that was most noticeable was the changes in eating (Bozeat et al., 2000, Snowden et al., 2001). Many individuals, according to the surveys, struggled with controlling weight gain, ate to excess and ate everything that was present in front of them. In a study looking at the differences between Frontotemporal dementia and Alzheimer s disease, researchers found that 30% of people diagnosed with Frontotemporal dementia gained 7.5 kg (16 pounds) or more as compared to only 7% of people with Alzheimer s disease (Ikeda et al., 2002). With almost three times the 1

percentage of people demonstrating significant weight gain in Frontotemporal dementia as compared to Alzheimer s disease, it is clear that the underlying neuropathology in each disease must progress differently and attack different regions of the brain. Researchers have attempted to find out how and where the brain mediates normal levels of food consumption. Most adults maintain a constant weight throughout their life suggesting that there is regulation of eating. Many theorize that food intake is controlled to match energy intake and expenditure so that weight homeostasis is facilitated throughout the adult life (Shin et al., 2009). In order to facilitate this homeostasis, many researchers have speculated that there is a neurological control network responsible for the maintenance of weight and food intake. Studies have shown that during eating, the body releases hormones to decrease the drive to eat. One of these hormones is leptin which act on leptin-sensitive neurons in the hypothalamus. When leptin reaches the corresponding receptors, it acts as an inhibitor for eating. This region of the brain acts as a relay station of many hormones from the brainstem (Shin et al., 2009). In order to maintain appropriate levels of food consumption, the hypothalamus must integrate signals such as those from leptin levels by decreasing the consumption of food when leptin levels rise. Not only does the hypothalamus regulate eating but it is an area that integrates and disperses signals from many regions of the brain. The act of eating in humans is a highly regulated phenomena that is motivated by the integration of many signals from the body. Specifically, eating involves: reward, motivation, learning and memory and sensory input from olfaction, visual stimuli and motor coordination (Shin et. al., 2009). Each of these processes are mediated by a different region of the brain. Despite this, all of the neurological signals are relayed through the hypothalamus (Morton et al., 2

2006, Shin et al., 2009). With several integration networks running through the hypothalamus, damage to this region could result in changes in eating behavior. In their study attempting to create distinct profiles for Frontotemporal dementia, some of the most striking pieces of information was the frequency of overeating, eating continually if food was in front of them, and cramming of food. For Frontotemporal dementia the frequencies were 83% for overeating, 50% for continuous eating when food is present, and 50% for food cramming. With such large percentages of people diagnosed with Frontotemporal dementia suffering these same symptoms, a body of research has looked into explaining these bizarre eating patterns. All of the behaviors listed are in direct contrast to normal eating patterns in humans. Humans consume food in discrete bouts or meals in a process that is regulated by saiety signals that are sent to the brain when food is ingested (Morton et al., 2006). Eating everything that is present is a feature of Frontotemporal dementia that is in direct contrast to the homeostasis discussed by researchers studying typical patterns of eating. Not only did half the people eat everything in front of them but half also crammed food both of which are not necessary components of normal consumption. Both of these factors suggest that people diagnosed with Frontotemporal dementia have some neuropathology that causes their eating patterns to deviate from the norm. Researchers attempting to explain this phenomena have looked into the underlying neurological changes and attempted to explain it through atrophy of the temporal region, specifically the posterior hypothalamus (Ikeda et al., 2002). Such striking changes in behavior would be expected to stem from profound levels of damage to the hypothalamus. Other groups have also measured the changes in the posterior hypothalamus through examining postmortem autopsies of people who had Frontotemporal dementia. On average the 3

hypothalamus size decreased by 35% as compared with healthy controls (Piguet et al., 2011). Along this same line, higher levels of disturbance to feeding were noted with smaller posterior hypothalamus compared to people with less change in eating behavior. Differing levels of atrophy in the hypothalamus had equivalent levels of behavioral changes in eating (Piguet et al., 2011). This group also used fmri imaging to look at the hypothalamus and found that decreases in size and integrity could be distinguished within 2 years of the original diagnosis of Frontotemporal dementia (Piguet et al., 2011). If changes in eating could occur that early in the pathology of this disease and only more neural atrophy occurring throughout its progression, it is likely that the symptoms of overeating will worsen with time. Along with atrophy in the hypothalamus, researchers have noted that damage also occurs in the frontal lobes of the brain. Like the changes that damage to the hypothalamus cause; damage to the frontal lobes can be linked to distinct behavioral changes. Another salient change in behaviors for many people diagnosed with Frontotemporal dementia is the decrease in control of impulsivity. Scientists believe that changes in inhibition control can be caused by the atrophy seen in Frontotemporal dementia. Specific regions in the frontal lobes that are compromised by atrophy include the orbitomedial parts of the frontal lobes as well as the temporal poles. Damage to these areas can cause a variety of behavioral changes and can account for the heterogeneous nature of Frontotemporal dementia (Snowden et al., 2001). With many connection pathways flowing between the frontal lobe and the hypothalamus, it is logical that damage to both would cause even more extreme behavioral changes. One of the factors found in Frontotemporal dementia is a lack of inhibition control. Atrophy to the orbitomedial parts of the frontal lobes can account for some of the changes in inhibition. The loss of inhibitory pathways in the brain can lead to overactivity of peptidergic 4

pathways and the consequent feeding disturbances in Frontotemporal dementia (Piguet et al., 2011). One of the major roles of inhibition control the levels and expression of hormones and peptides. When damage occurs to the regions responsible for inhibition control, higher levels of peptides and hormones build up. In turn this causes the brain to signal to continue eating. Not only do people continue to eat but when examining swallow studies of people with Frontotemporal dementia, the patients also took in larger boluses than normal (Langmore et al., 2007). With overeating, cramming and consuming larger boluses as hallmarks of Frontotemporal dementia it seems reasonable that these factors could lead to dysphagia and other health complications as a result. Overeating with little to no inhibition and behaviors such as cramming and eating everything available puts people at increased risk for dysphagia. In a study that compared healthy controls to matched people with Frontotemporal dementia, two distinct swallowing behaviors emerged in the latter group. People with Frontotemporal dementia allowed excessive time of food leakage into the pharynx during mastication. Healthy control groups had a mean time of leakage of 1.20 seconds as compared to 3.06 seconds on average for the Frontotemporal dementia group. One person with Frontotemporal dementia had 45 seconds of leakage time into the pharynx before a swallow (Langmore et al., 2007). Consequently with longer leakage time, the bolus were able to travel further down the pharynx before a swallow was initiated. If not cleared properly the bolus could penetrate the airway. Another unexpected finding was the clearance of bolus. In healthy controls, pharyngeal clearance was complete as compared to people with Frontotemporal dementia where one third of people had residual (Langmore et al., 2007). Both of these changes in swallowing comparing healthy controls to people with Frontotemporal dementia show how people with Frontotemporal dementia are in danger for 5

airway penetration and potentially complications of aspiration such as pneumonia. During the course of the study, only one person aspirated during the swallow examination. The researchers did however speculate that the incidence was low because participants were only allowed to consume controlled amounts of food and if they were allowed to eat everything in front of them, cramming could have led to higher levels of aspiration (Langmore et al., 2007). More research is needed in how people with Frontotemporal dementia manage food leakage and residual clearance. It is clear however that the changes in eating patterns can put people at risk for other health complications other than weight gain. Atrophy in both the frontal and temporal lobes in Frontotemporal dementia cause profound and drastic changes to eating behaviors. Through the atrophy of the posterior hypothalamus, the processing of peptides and hormones is disrupted. This combined with decreases in inhibition control lead to overeating, cramming and finally dysphagia that is not observed in healthy age-matched controls. Clinicians encountering people who have been diagnosed with Frontotemporal dementia will have to assess not only social and communication skills but also assess the eating habits. When encountering patients with similar changes in behaviors as listed above, clinicians must monitor eating for penetration and aspiration to ensure the best quality of life for their patients. 6

Works Cited Bozeat, S., Gregory, C., Lambon Ralph, M., & Hodges, J. (2000). Which neuropsychiatric and behavioural features distinguish frontal and temporal variants of frontotemporal dementia from Alzheimer's disease? J Neurol Neurosurg Psychiatry, 69, 180-185. Ikeda, M., Brown, J., Holland, A., Fukuhara, R., & Hodges, J. (2002). Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer's disease. J Neurol Neurosurg Psychiatry, 73, 371-375. Langmore, S., Olney, R., Lomen-Hoerth, C., & Miller, B. (2007, January). Dysphagia in Patients with Frontotemporal Lobar Dementia. Arch Neurol, 64, 58-62. Morton, G., Cummings, D., Baskin, D., Barsh, G., & Schwartz, M. (2006, September 21). Central nervous system control of food intake and body weight. Nature, 443, 289-294. Piguet, O., Petersen, A., Yin Ka Lam, B., Gabery, S., Murphy, K., Hodges, J., & Halliday, G. (2011, February). Eating and Hypothalamus Changes in Behavioral-Variant Frontotemporal Dementia. Annuals of Neurology, 69(2), 312-318. Shin, A., Zheng, H., & Berthoud, H. (2009). An expanded view of energy homeostasis: Neural integration of metabolic, cognitive, and emotional drives to eat. Physiology and Behavior, 97, 572-578. Snowden, J., Bathgate, D., Varma, A., Blackshaw, A., Gibbons, Z., & Neary, D. (2001). Distinct behavioural profiles in frontotemporal dementia and semantic dementia. J Neurol Neurosurg Psychiatry, 70, 323-332. 7