New research suggests that the decreased ability to identify certain odors may signal early-stage Alzheimer’s disease and future cognitive decline.

The test – dubbed the University of Pennsylvania Smell Identification Test – was the focus of two studies presented at the Alzheimer’s Association International Conference in Toronto. Both studies were funded by the National Institute on Aging.

The memory area is the same area in the brain where odor information is stored. The lowest smell recognition has the greatest risk for Alzheimer’s disease.  Loss of sense of smell for peanut butter can be indicative of the presence of Alzheimer’s.

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Olfactory sensory neurons project axons to the brain within the olfactory nerve, (cranial nerve I). These nerve fibers, lacking myelin sheaths, pass to the olfactory bulb of the brain through perforations in the cribriform plate, which in turn projects olfactory information to the olfactory cortex and other areas. The axons from the olfactory receptors converge in the outer layer of the olfactory bulb within small (~50 micrometers in diameter) structures called glomeruli.

Mitral cells, located in the inner layer of the olfactory bulb, form synapses with the axons of the sensory neurons within glomeruli and send the information about the odor to other parts of the olfactory system, where multiple signals may be processed to form a synthesized olfactory perception.

A large degree of convergence occurs, with twenty-five thousand axons synapsing on twenty-five or so mitral cells, and with each of these mitral cells projecting to multiple glomeruli. Mitral cells also project to periglomerular cells and granular cells that inhibit the mitral cells surrounding it (lateral inhibition).

Granular cells also mediate inhibition and excitation of mitral cells through pathways from centrifugal fibers and the anterior olfactory nuclei. Neuromodulators like Acetylcholine, Serotonin and Norepinephrine all send axons to the olfactory bulb and have been implicated in gain modulation, pattern separation and memory functions, respectively.

The mitral cells leave the olfactory bulb in the lateral olfactory tract, which synapses on five major regions of the cerebrum: the anterior olfactory nucleus, the olfactory tubercle, the amygdala, the piriform cortex, and the entorhinal cortex. The anterior olfactory nucleus projects, via the anterior commissure, to the contralateral olfactory bulb, inhibiting it.

The piriform cortex has two major divisions with anatomically distinct organizations and functions. The anterior piriform cortex (APC) is better associated with determining the chemical structure of the odorant molecules and whereas the posterior piriform cortex (PPC) is best known for its strong role in categorizing odors and assessing similarities between odors (e.g. minty, woody, citrus are odors which can be distinguished via the PPC despite being highly-variant chemicals and in a concentration-independent manner).

The piriform cortex projects to the medial dorsal nucleus of the thalamus, which then projects to the orbitofrontal cortex. The orbitofrontal cortex mediates conscious perception of the odor. The 3-layered piriform cortex projects to a number of thalamic and hypothalamic nuclei, the hippocampus and amygdala and the orbitofrontal cortex but its function is largely unknown. The entorhinal cortex projects to the amygdala and is involved in emotional and autonomic responses to odor. It also projects to the hippocampus and is involved in motivation and memory.

Odor information is stored in long-term memory and has strong connections to emotional memory. This is possibly due to the olfactory system’s close anatomical ties to the limbic system and hippocampus, areas of the brain that have long been known to be involved in emotion and place memory, respectively.