Our nose helps us identify odors, from a cup of coffee to the smoke of a cigarette. As we age, an impaired sense of smell is normal, but completely losing our sense of smell could be a sign of brain damage.

Two studies presented at the Alzheimer's Association International Conference 2016 in Toronto, Canada, found the University of Pennsylvania Smell Identification Test (UPSIT) may be effective in predicting cognitive decline, and detecting early stages of Alzheimer's disease. In both cases, elderly people who took a standard odor detection test performed poorly, and were more likely to have or go on to develop problems with memory loss and thinking.

In the first study, researchers administered a smell test to 400 older, dementia-free adults who were an average age of 80. The participants also underwent an MRI scan to measure the thickness of the entorhinal cortex — the first area of the brain to be affected by Alzheimer’s. Four years later, 12.6 percent of participants had developed dementia, and nearly 20 percent showed signs of cognitive decline.

The researchers noted low smell identification test scores, not entorhinal cortical thickness, were associated with dementia and Alzheimer’s disease. Low scores indicate a decreased ability to correctly identify odors. However, entorhinal cortical thickness was significantly associated with a low score in those who transitioned to dementia.

In the second study, the researchers administered a smell test and performed either beta amyloid positron emission tomography (PET) scanning or a spinal tap in order to analyze the cerebrospinal fluid in 84 older adults with an average age of 71. Beta-amyloid plaques are considered the “hallmarks of Alzheimer's disease"; they build up between nerve cells in the brain and block cell-to-cell signaling at the synapses, which can activate immune system cells that trigger inflammation, and consume disabled cells. PET scans reveal plaque in the brain, while spinal taps show plaque in cerebrospinal fluid.

Of these participants, 58 had mild cognitive impairment. The adults were followed for at least a period of six months.

The findings revealed PET scanning and cerebrospinal fluid more accurately predicted memory decline while the smell identification test didn’t. However, participants with a smell test score of less than 35 were more than three times as likely to have memory decline than those with a score higher than 35.

"Our research suggests that both UPSIT score and amyloid status predict memory decline," said Dr. William Kreisl, an assistant professor of neurology at Columbia University Medical Center (CUMC), and a neurologist at NewYork-Presbyterian/Columbia, in a statement.

Right on the nose

The smell test could offer an alternative to costly and painful methods of detecting Alzheimer’s, and work to spot the disease in its early stages. As of now, current testing methods can only detect it after significant bran damage has occurred. An odor test could make it for feasible for patients to get tested, treated, and keep cognitive decline at bay.

"Our study adds to the growing body of evidence demonstrating the potential value of odor identification testing in the detection of early-stage Alzheimer's disease," said Dr. D.P. Devanand, senior author of both studies, and a professor of psychiatry at CUMC, in a statement.

Detecting Alzheimer's in its early stages is not simple. Failing memory, such as forgetting which day it is and remembering later, is par for the course as we age. Meanwhile, other signs, such as being confused about the past or present, may appear after the disorder has damaged the brain.

Now, the two research groups from CUMC believe a simple odor test could be a more effective and a less expensive, invasive method to detect the crippling disease that affects 5.4 million Americans, and 44 million people worldwide.

Earlier this year, a simple urine test was found to predict the onset of Alzheimer’s in a group of mice. Researchers gave the rodents a chemical treatment meant to mimic the abnormal brain activity of people with the disease. These mice were found to have a unique urine odor that was detectable even before researchers could identify plaque build-up in the mice’s brains. This suggests odor is due to a genetic change rather than a developmental one, meaning the disease could be detected earlier than previously believed.

Although there is no test to detect Alzheimer’s, the presence of early biomarkers, such as a loss of smell or a distinct urine smell, could allow doctors to delay the progression of the disease, while exploring other forms of treatment.

Source: Lee S et al. Predictive Utility of Entorhinal Cortex Thinning and Odor Identification Test for Transition to Dementia and Cognitive Decline in an Urban Community Population. AAIC 2016 Toronto, Canada.

Kreisl W et al. Both Odor Identification and Amyloid Status Predict Memory Decline in Older Adults. AAIC 2016 Toronto, Canada.