Olfactory Imaging Probes of Alzheimer's Disease

Recent studies indicate that patients with Alzheimer’s disease (AD) exhibit profound impairments in the sense of smell. Deficits of odor discrimination, identification, and memory, in the absence of elementary olfactory dysfunction, are commonly observed in early stages of AD and may even pre-date the onset of more classical symptoms. The impaired sense of smell likely reflects the anatomical intersection of AD pathology with limbic brain regions implicated in olfactory processing, including entorhinal cortex, amygdala, and piriform cortex. These findings provide compelling evidence that the olfactory system is susceptible to the pathological effects of AD, and that this vulnerability is manifested early in disease. An important implication is that odor stimuli might be effectively used as biological probes of limbic dysfunction in the setting of AD, providing a potential non-invasive diagnostic marker of AD onset and progression.

Using an olfactory version of fMRI cross-adaptation, our lab has begun testing the hypothesis that odor quality codes in piriform cortex are degraded in patients with AD. Specifically, the prediction is that in age-matched control subjects, the presentation of qualitatively similar (vs. qualitatively different) odorants will elicit cross-adapting (decreased) neural activity in olfactory limbic areas, whereas in AD patients, the sensitivity of fMRI cross-adaptation to odor quality will be lost, reflecting the disorganization of odor quality codes in brain regions that are early targets of AD pathology. Our preliminary results support the idea that neural information about odor quality is disrupted in limbic olfactory regions that are early targets of AD pathology, and that there is a reduction in the volume of piriform cortex with preserved quality-adaptive fMRI responses. Together these findings suggest that olfactory fMRI is a sensitive probe of limbic olfactory dysfunction in AD, and further efforts will explore the predictive validity of these measures in patients in the earliest stages of memory loss.