A new study has found that the loss of smell could be an early warning sign of Alzheimer’s disease, and the timing of diagnosis could help at-risk patients receive more effective treatment.
The research, conducted by DZNE and Ludwig-Maximilians-Universität München (LMU), found that Alzheimer’s can cause the brain’s immune cells, called microglia, to mistakenly target healthy nerve fibers in the brain that are crucial for smell. This means an Alzheimer’s patient will likely struggle to smell years before they are formally diagnosed with the disease.
The connection between scent and Alzheimer’s has been theorized for years, but the study’s findings are a promising sign that neurologists may start testing the sensitivity of smell in patients, Dr. Dale Bredesen, a neurologist at Apollo Health with a focus on Alzheimer’s disease, told HuffPost.
“The question has always been, ‘Why is [smell loss] such an early change in Alzheimer’s?’” Bredesen said. “I think this [study] will help to let neurologists know we should be more sensitively testing smell in people routinely before they ever have any cognitive complaints.”
One of the earliest sites degenerated in Alzheimer’s disease is called the locus coeruleus, which is a spot in the brain stem that provides the brain with norepinephrine, Bredesen explained. Norepinephrine helps regulate functions like smell, sleep and blood flow.
The research team used mouse models, human brain tissue from deceased patients and PET brain scans from living Alzheimer’s patients to try to figure out how and why Alzheimer’s disease is linked to smell.
They found that Alzheimer’s triggers abnormal neuron firing, which causes phosphatidylserine — a molecule normally found on the inside of neuron membranes — to shift to the outside. This shift essentially tricks microglia into thinking that the fibers are issuing out an “eat-me” signal and need to be removed. The microglia attack the fibers connecting the locus coeruleus to the olfactory bulb, the neural structure in the forebrain that controls the sense of smell, which is why smell loss is one of the first features to deteriorate.
“[The study] brings this all together and shows that the locus coeruleus damage, the loss of sense of smell … is probably related to energy,” Bredesen said, based on his own expertise in the field. “So the new insight says, ‘Hey neurologists, please, look more carefully and more quantitatively at the sense of smell because this can be another of the early warning signs.’”
If you’re at risk for Alzheimer’s, experts recommend asking for a smell test.
Current Alzheimer’s treatments, like amyloid-beta antibodies, have been found to work best when given to patients as early as possible. If smell tests could help flag at-risk patients years ahead of their memory loss symptoms, neurologists could potentially slow the disease’s progression.
“With all these complex chronic illnesses, things are changing when you can pick them up earlier and do something about it,” Bredesen said.
Bredesen compared it to the hemoglobin A1C, which came out 50 years ago and has changed the landscape of pre-diabetes diagnoses, and biomarkers like the P-tau217, which can help identify potential Alzheimer’s patients over 20 years before the onset of symptoms.
This is also “essentially what happened with Pap smears many, many years ago,” he said, referring to the potential of these smell tests. “You went from a disease where you would find it late, and women would die from it.” (While cervical cancer remains a significant health threat, it is now a highly preventable and curable condition when found early, and deaths have dropped over 50% since the 1970s due to Pap smears.)
Bredesen insists that anyone over the age of 35 who has a family history of brain cognitive conditions could ask their neurologist to have their sense of smell tested. Lifestyle factors ― like exercise, eating nutritious foods and social interactions ― remain an important part of prevention as well.
And, most importantly, know that a smell test is not a guaranteed answer for at-risk patients. Bredesen emphasized that studies like this one are shifting neurologists and doctors in the right direction, but anyone at risk of Alzheimer’s should not assume that if they pass a smell test, they’re 100% in the clear.
“If you start noticing some decrease in your smelling ability, please get to a doctor,” he said. “Don’t assume that it’s a benign condition.”