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3500万美国人年龄超过60岁，最年长的老年人是美国人口中增长最快的部分。老年人是保健服务的更经常消费者，在健康不佳时，老年人是长期护理设施的消费者。这些服务的费用相当可观。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年）。虽然老年人的虚弱和体重减轻是虚弱和死亡的不良预后因素，但中年肥胖症的流行性增加与心血管疾病、糖尿病、痴呆和“代谢综合征”的相关风险正在产生巨大的公共卫生负担，对下一代老年人具有严重影响（Poirier et al.，2006年）。中年肥胖者在晚年入住疗养院的风险更高，因此降低肥胖率可以减少疗养院护理的后期社会负担（埃尔金斯等人，2006年）。明确阐明年龄相关的变化，大脑对食欲刺激的反应，在饥饿和饱腹感，可能会建议干预措施，以调节食物摄入量，肥胖的中年和老年人的脆弱。与肥胖相似，阿尔茨海默病（AD）是一种病理过程，其风险存在于中年，严重后果出现在老年。由于APOE e4等位基因而具有AD遗传风险的非痴呆老年人的生物行为标志物对于临床前阶段的疾病信号具有潜在的临床意义。AD患者表现出早期和显著的记忆丧失，特别是气味记忆丧失，并且他们在老年时表现出严重的嗅觉功能障碍（Murphy等人，1990年）。化学感觉、行为和代谢异常导致营养不良和体重减轻，进一步增加了这种不稳定疾病人群的发病率（Guirin等人，2005;综述于Wenish等人，2001年）。尽管澄清的重要性，在与年龄相关的进展的肥胖和阿尔茨海默氏病的过程中，营养畸变的中央过程的影响，在这两个人口的化学感觉功能和大脑处理被直接解决在中年队列。神经影像学是唯一的方法，能够揭示精确的空间信息与年龄相关的差异，在大脑皮层反应的化学感觉刺激在活着的人。本研究将使用功能磁共振成像的权力，以图像老化的大脑，而它是处理的味道和气味的信息，以测试的总体假设，中枢神经系统活动的功能变化，检测功能磁共振成像的皮质表示，构成一个主要的神经基板改变化学感觉功能和偏好在正常老化和AD。更好地了解化学感觉功能和偏好可能会建议途径，以优化健康和老年美国人的生活质量。公共卫生相关性：中年肥胖症已经成为一种流行病，具有严重的公共卫生后果，并且“代谢综合征”是一组密切相关的疾病，其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，影响大多数发达国家四分之一的成年人（Poirier et al.，2006年）。肥胖导致人均医疗保健支出增加约50%，成本随着年龄和肥胖程度而增加，并且由于中年肥胖与老年慢性疾病、未来痴呆、住院和疗养院入院的增加有关，因此降低肥胖率可以减少长期疗养院护理的后期社会负担（埃尔金斯等人，2006; Whitmer等人，2005年）。阐明大脑对食欲化学感觉刺激反应的年龄相关变化可能表明调节中年食物摄入和肥胖以及老年人代谢疾病和认知障碍的途径。

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.