Chemosensory Perception and Psychophysics in the Aged

描述(由申请人提供)：最佳的健康、功能和营养状况是美国老年人生活质量的关键。超过3500万美国人年龄在60岁以上，年龄最大的老年人是美国人口中增长最快的部分。老年人更频繁地使用保健服务，当健康状况不佳时，也更频繁地使用长期护理设施。这些服务的成本是相当高的。味觉和嗅觉功能受损会对老年人的饮食选择、营养状况、发病率和死亡率产生负面影响(Schiffman，1997)。虽然老年人的虚弱和体重减轻是虚弱和死亡的不良预测因素，但中年肥胖症的流行增加以及与心血管疾病、糖尿病、痴呆症和“代谢综合征”相关的风险正在造成巨大的公共卫生负担，并对下一代老年人产生严重影响(Poirier等人，2006年)。中年肥胖者在晚年入住养老院的风险更高，因此降低肥胖率可能会减少后来养老院护理的社会负担(Elkins等人，2006年)。明确阐明饥饿和饱腹期间大脑对食欲刺激反应的年龄相关变化，可能会建议进行干预，以调节食物摄入量、中年人的肥胖和老年人的虚弱。与肥胖类似，阿尔茨海默病(AD)是一种病理过程，中年存在风险，老年出现严重后果。在非痴呆老年人中，由于APOE e4等位基因而存在AD遗传风险的生物行为标记物对临床前期的信号疾病具有潜在的临床意义。AD患者表现出早期和戏剧性的记忆丧失，特别是气味记忆，他们在老年表现出严重的嗅觉功能障碍(Murphy，et al.，1990)。化学感觉、行为和代谢异常导致营养不良和体重减轻，进一步增加了这一危险疾病人群的发病率(Guirin等人，2005年；Reynish等人，2001年综述)。尽管在肥胖和阿尔茨海默病的与年龄相关的进展过程中，阐明中央过程对营养异常的影响很重要，但在这两个人群中，化学感觉功能和大脑处理都没有在中年队列中直接得到解决。神经成像是唯一能够揭示活人大脑皮质对化学感觉刺激反应的年龄相关差异的精确空间信息的方法。本研究将使用功能磁共振成像的能力，在处理味觉和气味信息的同时对老化的大脑进行成像，以检验最重要的假设，即中枢神经系统活动的功能变化，可在功能磁共振成像的皮质表征中检测到，构成正常衰老和AD患者化学感觉功能和偏好改变的主要神经底物。对化学感觉功能和偏好的更好理解可能会为优化美国老年人的健康和生活质量提供途径。与公共健康相关：在大多数发达国家，中年肥胖已经成为一种流行病，具有严重的公共健康后果和“代谢综合征”，这是一组密切相关的疾病，会使心血管疾病的风险增加一倍，糖尿病的风险增加两倍，并影响认知功能，影响四分之一的成年人(Poirier等人，2006年)。肥胖导致人均医疗保健支出增加约50%，费用随着年龄和肥胖程度的增加而上升，而且由于中年肥胖与慢性病、未来的痴呆症、住院和老年疗养院入院的增加相关，因此降低肥胖率可能会减少后来长期疗养院护理的社会负担(Elkins等人，2006年；惠特默等人，2005年)。阐明大脑对食欲化学感觉刺激的反应与年龄相关的变化，可能会为调节中年人的食物摄入量和肥胖，以及老年人的代谢性疾病和认知障碍提供途径。

Description (provided by applicant): Optimum health, functioning and nutritional status are key to the quality of life in the older American. More than 35 million Americans are over the age of 60, and the oldest old represent the fastest growing segment of the American population. Older persons are more frequent consumers of health care services and, when health fails, of long-term care facilities. The costs of these services are considerable. Impairment of taste and olfactory function can negatively impact dietary selection, nutritional status, morbidity and mortality in older persons (Schiffman,1997). While frailty and weight loss in the elderly are poor prognostic factors for debility and mortality, epidemic increase in middle-aged obesity with associated risk for cardiovascular disease, diabetes, dementia and "metabolic syndrome" is creating an enormous public health burden with grave implications for the next generation of older adults (Poirier et al., 2006). The middle aged obese have a higher risk of nursing home admission in late life and reducing obesity rates may thus reduce the later societal burden of nursing home care (Elkins et al., 2006). Clear elucidation of age-related changes in brain response to appetitive stimuli, during hunger and satiety, may suggest interventions to modulate food intake, obesity in middle aged and frailty in older adults. Similar to obesity, Alzheimer's disease (AD) is a pathologic process for which risk exists in middle age and severe consequences emerge in old age. Bio-behavioral markers in non-demented older adults at genetic risk for AD because of the APOE e4 allele have potential clinical significance for signaling disease in the pre- clinical period. AD patients show early and dramatic loss of memory, and particularly odor memory, and they demonstrate profound olfactory dysfunction in old age (Murphy, et al., 1990). Chemosensory, behavioral, and metabolic abnormalities lead to malnutrition and weight loss, furthering morbidity in this precarious disease population (Guirin et al, 2005; reviewed in Reynish et al., 2001). Despite the importance of clarifying the impact of central processes on nutritional aberrations in the age-related progression of both obesity and Alzheimer's disease processes, in neither population has chemosensory function and brain processing been directly addressed in a middle-aged cohort. Neuroimaging is the only method capable of revealing precise spatial information about age-related differences in cortical response to chemosensory stimuli in living humans. The present study will use the power of fMRI to image the aging brain while it is processing taste and odor information in order to test the overarching hypothesis that functional changes in central nervous system activity, detectable in the cortical representation on fMRI, constitute a major neural substrate for altered chemosensory function and preference in normal aging and AD. A better understanding of chemosensory function and preference may suggest avenues to optimize health and qualify of life in aging Americans. PUBLIC HEALTH RELEVANCE: Middle aged obesity has become an epidemic with serious public health consequences and the "metabolic syndrome," a cluster of closely related disease states that doubles risk of cardiovascular disease, triples risk of diabetes, and impacts cognitive function, affects one in four adults in most developed countries (Poirier et al., 2006). Obesity is responsible for increased per capita health care spending of approximately 50%, with costs rising by age and degree of obesity, and because midlife obesity is associated with increased chronic illnesses, future dementia, hospitalizations, and nursing home admission in old age, reducing obesity rates may thus reduce the later societal burden of long-term nursing home care (Elkins et al., 2006; Whitmer et al., 2005). Elucidation of age-related changes in brain response to appetitive chemosensory stimuli may suggest avenues to modulate food intake and obesity in middle age, and metabolic disease and cognitive impairment in older adults.