Can a Smell Test Sniff Out Alzheimer's Disease?

The sense of smell is one of the first things to change as Alzheimer’s disease takes root, even before other symptoms appear. That’s raised the idea that a scratch-and-sniff test that rates an individual’s ability to identify odors could potentially detect the disease early—allowing patients to begin treatment before symptoms become harder to treat. Columbia neurologist William Kreisl, MD, has been studying a smell identification test and explains what it can—and can’t—say about Alzheimer’s.

What’s the connection between smell and Alzheimer’s disease?

The olfactory bulb—which sends smell information from the nose to the brain—is one of the first areas of the brain to sustain damage in Alzheimer’s disease. Brain areas that receive information from the olfactory bulb, such as the entorhinal cortex, are also affected early in the disease. As a result, impaired ability to recognize odors often occurs in people with early-stage Alzheimer’s before memory symptoms are noticed.

Previous studies have suggested that individuals who scored poorly on the smell test were more likely to have had neurodegenerative changes in the brain caused by Alzheimer’s, such as a buildup of beta amyloid deposits, or plaques.

Can the smell identification test tell me right now if I’m going to get Alzheimer’s?

No. Although the previous studies demonstrated that inability to identify odors correlates with memory decline, those studies didn’t tell us if the test could predict whether a particular individual will develop Alzheimer’s.

We recently performed a small study—including some individuals with mild memory problems and some without—to investigate the predictive power of the test. We found that those who did well on the test, meaning they had no difficulty identifying odors, didn’t have Alzheimer’s disease. We also found that those who had odor impairment were more than three times as likely to have memory decline a few months later compared with those who didn’t.

But we can’t say for sure whether the memory decline was due to Alzheimer’s or other neurodegenerative diseases that can damage the olfactory bulb, like Parkinson’s, Lewy body dementia, or Huntington’s.

We think this is a good first study in looking at the ability of smell test to predict memory decline, but we would need to replicate our findings in a larger study.

What role do you see the smell test playing in medicine?

More patients are asking doctors about their risk of Alzheimer’s disease. Currently, the only way to definitively diagnose the disease is postmortem, with an autopsy to look for a buildup of the proteins beta amyloid and tau—two biological markers for Alzheimer’s. To diagnose Alzheimer’s in living patients, we use a variety of surrogate tests, including PET scans that can detect beta amyloid deposits in the brain. But while PET scans are FDA-approved, they are expensive.

The smell test may offer a quick, easy, and inexpensive way to give patients some reassurance, by telling them whether they are in a low- or high-risk category, potentially sparing some patients from getting the more invasive million dollar workup. In fact, in our study no subject in the unimpaired smell group had evidence of amyloid deposits on PET scan, suggesting that older adults with strong odor recognition are at lower risk of Alzheimer’s disease.

The test could also make it easier and less expensive for clinical trials to develop new Alzheimer’s drugs by determining who should get a PET scan to look for beta amyloid plaques.

Is the smell test for everyone or just for older people showing signs of memory trouble?

The test is most helpful when someone has a memory complaint and they want to be evaluated. You need some context in order to properly evaluate patients, so someone without a memory complaint or a family history of dementia wouldn’t necessarily benefit from the test.

The test can be purchased online and done at home, but right now it’s mainly used in research. It may not be helpful unless you have a doctor to help interpret the results.

Are there other tests that may be able to predict dementia and/or Alzheimer’s disease?

In our study, we found that the smell test was comparable to PET scans in predicting an individual’s risk for memory decline. However, only 60 percent of those who got a low score on the smell test had beta amyloid plaques. Other studies have shown that not everyone who is positive for beta amyloid on a PET scan develops memory loss.

The bottom line is that it’s still difficult to predict memory decline. The smell test, like a PET scan, can help predict the risk of memory decline. But unlike a PET scan, it can’t tell you whether your memory decline may be due to Alzheimer’s or another neurodegenerative disease.

Getting a low score on the smell test isn’t the only factor to consider—clinicians also need to weigh family history and genetic risk factors while ruling out non-neurodegenerative causes of odor impairment, such as smoking. Because the smell test is inexpensive and easy to administer, they may want to use it to help determine if a more expensive, invasive workup is needed.

References

William Kreisl is the Boris and Rose Katz Assistant Professor of Neurology (in the Taub Institute) at Columbia University Vagelos College of Physicians & Surgeons. His most recent study, titled “Odor Identification Ability Predicts PET Amyloid Status and Memory Decline in Older Adults,” was published on March 27 in the Journal of Alzheimer’s Disease.