A Poor Sense of Smell May Point to Brain Trouble

New research ties dementia predictions to olfactory results



See the column on the Wall Street Journal site


If you can smell the difference between pineapple and paint-thinner, that’s a good sign: You may be more likely to keep your marbles well into the future. So says a new study on the predictive power of our sense of smell.

In a paper published in the journal Neurology in December, neurologist Kristine Yaffe and her team discovered that older adults with a keen sense of smell are less likely than their peers to develop dementia as they age. In contrast, a blunted sense of smell, much like an altered sense of humor or sense of direction, may presage more pervasive cognitive losses in the years ahead.

Previous research had led Dr. Yaffe, who is a professor of psychiatry and neurology at the University of California, San Francisco, to suspect that people with a diminished ability to identify odors might be at increased risk of dementia. Olfactory nerve fibers project into the brain’s centers for memory and emotional processing, which suggests a connection between those cells and smell-related ones.

Dr. Yaffe’s research team followed 2,428 healthy adults in their 70s, all participants in a national, ongoing study of aging. Previous studies on the topic were often confined to white populations. This time the research team created a group that was half black, half white as well as half male, half female.

Three years into the study, the researchers assessed the participants’ sense of smell using a standardized test of 12 common scents. The test required the subjects to inhale a series of airborne chemical compounds present in foods like onion, lemon and chocolate, as well as in environmental odors, such as smoke and gasoline. After each whiff, the subjects had to identify what they had just smelled, which resulted in their “odor identification score.”

The researchers then monitored the participants’ psychological and medical status for the next nine years, using a memory test and their medication and hospitalization records. The team controlled for other factors that could increase the risk of memory loss, such as a prior smoking habit, a history of head trauma, depression or a genetic predisposition for Alzheimer’s disease. With those factors statistically stripped away, the experimenters found that on tests for sense of smell, men trailed women slightly and blacks lagged a bit behind whites.

What mattered most, though, were comparisons within the racial and gender groups. People of either race or sex who had more trouble identifying smells were indeed more likely to develop dementia—despite having no signs of cognitive decline when they signed up for the study, nor during its first three years.

Among whites, the weakest smellers (the lowest third of the group) had three times the dementia risk as the highest third. Among black participants, the weakest group had two times the risk. Subtypes of dementia may explain the difference. Smell is a better early predictor of Alzheimer’s. Blacks, Dr. Yaffe said, have a greater risk of developing vascular dementia, which causes diffuse neural deficits, than Alzheimer’s, which leaves more tangles and plaques near the olfactory nerve.

“What’s happening,” she added, “is that abnormal proteins are building up over decades, and some of the early changes start in the olfactory bulb, the brain structure that receives neural information about odors. “When you think about how our brains evolved, it’s not a shocker that olfaction, considered an older part of the brain, would reflect degenerative processes first.”

In all, 491 of the participants developed dementia at the end of 12 years.

That a compromised sense of smell may be a biomarker for dementia is both good news and bad news. An early warning signal has limited use, since no drug yet exists to head off Alzheimer’s (though several medications are being developed that target its symptoms). Still, those who can’t smell shouldn’t panic. Researchers emphasize that a mildly dialed down sense of smell and taste—much like mild hearing loss—is just a feature of aging.