Detecting Alzheimer’s disease can be tricky, especially in its earliest stages. Alzheimer’s is frequently misdiagnosed, due in part to the expensiveness and complexity of the current diagnostic tools. According to a 2012 examination of the National Institute on Aging’s Alzheimer’s Disease Centers, physicians may fail to detect more than 1 in 10 Alzheimer’s cases.
Alarmingly, some centers also had a false positive rate of more than 50%, meaning that half of the patients who were diagnosed with Alzheimer’s actually did not have the disease. The symptoms of these individuals may have been due to other conditions such as vascular dementia or thyroid dysfunction. An incorrect diagnosis could have resulted in the true cause of these patients’ memory loss going untreated (see Is It Really Alzheimer’s? 10 common misdiagnoses you should know about).
However, there might be a simpler and more cost-effective way to help diagnose Alzheimer’s disease: your sense of smell. As strange as it sounds, your nose can provide some key insight into the health of your brain.
Sniffing Out Dementia
Just like vision and hearing, our sense of smell tends to gradually deteriorate as we get older. Anosmia, the complete inability to smell, affects more than 50% of people over the age of 65 and 75% of people over 80. This likely contributes to the loss of appetite that many elderly people experience, as our sense of smell is closely tied to our ability to taste and enjoy food. Changes in the nose’s smell receptors and in the parts of the brain responsible for olfactory processing are likely to blame for age-related anosmia.
While anosmia is common among all elderly individuals, it seems to be especially prevalent in certain neurological conditions, including dementia. The frequency of anosmia among dementia patients has been known since the 1970s, but only recently has this observation begun to attract the attention of researchers.
The ability to identify different odors is frequently impaired in early-stage Alzheimer’s patients, with complete anosmia appearing in the later stages of the disease. A small study involving 90 patients with mild cognitive impairment found that individuals with greater olfactory impairment were more likely to progress to Alzheimer’s disease during the two-year study period. Many of these patients were unaware of their own inability to smell.
#AlzFact: Peanut butter might help identify early-stage Alzheimer’s. A small study from the University of Floria found that Alzheimer’s patients have difficulty smelling peanut butter, especially with the left nostril.
An olfactory assessment called the Pocket Smell Test has shown promise as a diagnostic tool for Alzheimer’s disease. In a small 60-patient study, this simple three-item test was able to distinguish Alzheimer’s from vascular dementia and major depressive disorder with 95% accuracy, a dramatic improvement from the 50% false-positive rate by NIA physicians that I described earlier. All of the Alzheimer’s patients in the study had two or three incorrect responses to the smell test, while nearly all of the vascular dementia and depression patients had zero or one incorrect response.
Another small study suggested that smell tests could also be used to distinguish Alzheimer’s from semantic dementia, frontotemporal dementia, and corticobasal dementia. Notably, smell tests would probably be less useful for distinguishing Alzheimer’s from Parkinson’s disease, since anosmia seems to be equally common in these two conditions. However, simple smell-detection tests could serve as an inexpensive method to improve the accuracy of Alzheimer’s diagnoses when combined with more traditional diagnostic tools.
Could Infections Be To Blame?
The reasons for the prevalence of anosmia in patients with Alzheimer’s or other dementias remain poorly understood. One interesting hypothesis, first proposed back in 1986, posits that the olfactory nerve (which transmits smell information from the nose to the brain) could serve as a potential entry point for environmental toxins or microbial agents to reach the brain. This has since been dubbed the olfactory vector hypothesis.
The brain is protected from external agents by the blood-brain barrier, which prevents most microbes and chemical substances from crossing between the nervous system and the blood. Olfactory neurons are unusual in that they are directly exposed to the external environment, making them vulnerable to infiltration. Unlike any other sensory cells, olfactory neurons connect directly to the brain without any intermediate synapses. Microbes can taken advantage of this direct connection as an ideal route to bypass the blood-brain barrier.
Olfactory neurons (shown in yellow) serve as a direct connection between the nasal cavity and the brain. Image source
Animal studies show that the viruses that cause polio, influenza, rabies, hepatitis, and herpes are all capable of infecting the brain via the olfactory nerve. In addition, many environmental toxins including metals, chemicals, and nanoparticles can be taken up by olfactory neurons and transported to the brain. This may help explain why prolonged exposure to air pollution or certain industrial chemicals can greatly increase the risk of Alzheimer’s (see Air Pollution, Aluminum, and Vitamin D Deficiency Linked to Dementia Risk).
The olfactory vector hypothesis remains a speculative model, and more evidence is needed to prove whether infiltration of the brain by external agents via the olfactory nerve can lead to Alzheimer’s. It is an intriguing idea that certainly warrants further study.
AlzScience 