Alzheimer’s disease pathology appears to start in the part of the brain that handles smell, before subsequently spreading to additional brain regions and then ultimately taking over much of the rest of the brain. That’s led some to speculate that Alzheimer’s disease may begin in the nose. Maybe there’s some environmental agent that might enter the brain through a portal in the nose.

This is the so-called olfactory vector hypothesis. The anatomy of the nose is well suited for the transfer of things directly into the brain, since the olfactory nerves that stick out into the nose project directly into the brain, bypassing the blood-brain barrier. That was actually a major infection route for the polio virus; in fact, public health officials started cauterizing the nasal passages of schoolchildren by spraying caustic chemicals up their noses in an effort to prevent the disease.

So the concern is if maybe people breathed in some aluminum dust or something, it could be transported into the brain through these nerves at a rate of like 2mm an hour, which is practically two inches a day. Doubt has been cast on this theory by a case report of a woman born with a birth defect in which she had no smell nerves, yet still developed Alzheimer’s-like pathology, and so to date all the supporting evidence is really just circumstantial. It is clear, though, that changes in the sense of smell are among the first clinical signs of Alzheimer’s, occurring during the “preclinical phase” before there’s any noticeable cognitive decline. So maybe we could use these changes to predict or diagnose the disease.

For years. researchers have been trying to find markers of brain illness hidden in people’s ability to smell, using all sorts of fancy gadgets.

Functional MRI scans can detect differences in brain activation in response to an odor, in this case lavender. This is what you see in a normal brain; this is what you see in an Alzheimer’s brain, unequivocally demonstrating that you can pick up changes in smell function due to Alzheimer’s–but do we really need a million-dollar machine?

An ingenious group of researchers at the University of Florida discovered all we may need is some peanut butter and a ruler.

Considering that the left side of the brain primarily processes what we smell through our left nostril, and the right side of our brain covers the right nostril, and Alzheimer’s strikes the left side more than the right, what if we performed the following experiment?

Close your eyes and mouth and breathe normally through the nose. Then close one nostril and hold a foot-long ruler out from the open nostril. After their eyes, mouth, and one nostril were closed, the container of peanut butter was opened at the bottom of the ruler and moved closer 1cm upon each exhale until the person indicated that they detected the odor. Then they repeated the whole procedure again using the other nostril.

In the normal elderly controls, they smelled the peanut butter as soon as it came within an average of 18 centimeters, which is about 7 inches from either nostril. And in the right nostril of Alzheimer’s patients was about the same, 7 inches. No difference; but in their left nostril, only 2 inches. The peanut butter had to get all the way up to 2 inches before they could detect it through their left nostril. And this happened every single time; left nostril impairment of odor detection was present in all the patients with probable Alzheimer’s disease. No left-right difference in the control group, but a 12cm difference in the Alzheimer’s group. The disparity was so great that one may be able to set a cutoff value for the diagnosis of Alzheimer’s. Compared to patients with other causes of dementia, this nostril asymmetry of odor detection was 100% sensitive and specific, meaning no false positives and no false negatives, and compared to healthy people 100% sensitive in picking up cases of Alzheimer’s, and 92% specific–meaning in this study, if you had Alzheimer’s, there was a 100% chance having a wide left-right discrepancy would show it, but if you had that discrepancy, the chances of having Alzheimer’s were 92%, meaning some false positives.

The reason they say “probable” Alzheimer’s is the only way you can really confirm if someone has it is on autopsy. The current criteria for diagnosing Alzheimer’s requires an extensive evaluation, combined with fancy PET scans or spinal taps. All of these tests are expensive and hard to get, can be invasive with potential complications, and on top of that are neither highly sensitive nor specific, unlike this quick, non-invasive and inexpensive left–right nostril peanut butter odor detection test, which may make it an ideal instrument for the early detection of Alzheimer’s disease.

To see any graphs, charts, graphics, images, and quotes to which Dr. Greger may be referring, watch the above video. This is just an approximation of the audio contributed by Katie Schloer.

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