Preliminary data from our positron emission tomographic (PET) studies suggests cerebral reorganization of human olfactory processing in healthy aging. This application requests pilot funds to verify this age-related reorganization, and to elucidate mechanisms of olfactory sensation, discrimination, and identification in the aging human brain. Olfaction declines in healthy aging, affecting quality of life and the ability to detect danger. Olfaction is also severely affected by Alzheimer disease (AD), in which mesial temporal olfactory cortex shows early degeneration. Correspondingly, we reported that olfactory stimulation during PET detects functional decline in mesial temporal lobe regions of AD patients (Kareken, et al., submitted). However, no research has used functional imaging to study normal age-related changes in cerebral olfactory networks. Imaging studies of young subjects report bilateral orbital and piriform activity in young subjects. Our preliminary study of healthy elderly found robust right piriform activity, and only weak left orbital activation. Therefore, our hypotheses are that: A) Right piriform cortex is activated by olfactory sensory stimulation in young and old subjects to an equivalent degree. B) Aging results in reduced left piriform and bilateral orbital activation during olfactory stimulation. C) Orbitofrontal and left piriform regions are more closely related to higher order olfactory tasks (discrimination and identification). D) Healthy elderly show reduced activity in these association areas during odor discrimination and identification.
Our specific aims are to: 1) Identify patterns of cerebral activation in young and old subjects during olfactory sensory stimulation. We will perform PET during suprathreshold olfactory stimulation in healthy young and older subjects. We will perform exploratory analyses to determine cortical regions that differ between younger and older subjects. 2) Characterize regional activation produced by odor discrimination and identification. We will study the same sample performing olfactory discrimination and identification tasks during PET. We will characterize regional activity produced by these tasks in young subjects, and compare their regional cerebral activation patterns to those of simple sensory stimulation. 3) Identify candidate regions involved in odor discrimination and identification that are affected by aging. We will compare the activation patterns of younger and older subjects during olfactory discrimination and identification tasks, and identify regions that show potential differences. These data will support application for further study through an R01 application. Findings from these studies can elucidate how the aging human brain changes its ability to process odor information. By examining these normal age related changes, we lay a foundation for understanding the early functional changes found in the temporal lobes of patients with AD.
| Kareken, David A; Sabri, Merav; Radnovich, Alexander J et al. (2004) Olfactory system activation from sniffing: effects in piriform and orbitofrontal cortex. Neuroimage 22:456-65 |
| Kareken, David A; Mosnik, Diane M; Doty, Richard L et al. (2003) Functional anatomy of human odor sensation, discrimination, and identification in health and aging. Neuropsychology 17:482-95 |
| Kareken, D A; Doty, R L; Moberg, P J et al. (2001) Olfactory-evoked regional cerebral blood flow in Alzheimer's disease. Neuropsychology 15:18-29 |
| Kareken, D A; Lowe, M; Chen, S H et al. (2000) Word rhyming as a probe of hemispheric language dominance with functional magnetic resonance imaging. Neuropsychiatry Neuropsychol Behav Neurol 13:264-70 |
