Your sense of smell and some eye tests can be an indicator of your susceptibility to Alzheimer’s. These were the results Harvard researchers came to in four recent trials, which found that people who have a harder time identifying odors might be experiencing cognitive impairment or even Alzheimer's disease. Meanwhile, examinations of the eye might indicate a build-up of beta-amyloid, a protein associated with Alzheimer's, in the brain.

The trials were reported on Sunday at the Alzheimer's Association International Conference 2014 in Copenhagen.

"In the face of the growing worldwide Alzheimer's disease epidemic, there is a pressing need for simple, less invasive diagnostic tests that will identify the risk of Alzheimer's much earlier in the disease process," said Dr. Heather Snyder, Alzheimer's Association director of medical and scientific operations, in a press release. "This is especially true as Alzheimer's researchers move treatment and prevention trials earlier in the course of the disease”

Two of the studies found that a decreased ability to identify odors was significantly associated with declining memory function and the progression to Alzheimer’s. The other two studies found that levels of beta-amyloid in the eyes correlated to levels of beta-amyloid in the brain, allowing researchers to accurately identify people with Alzheimer's. Beta-amyloid are the main components of the amyloid plaques that form deposits in the brain. Prolonged accumulation of these plaques are believed to result in Alzheimer’s, and typical symptoms like memory loss and reduced cognition progressively appear.

Current methods to detect Alzheimer’s do so only after the disease has progressed to a certain extent, at which point significant brain damage would have already occurred. While there are biological markers to detect Alzheimer’s at an early stage, they are expensive and not readily available. These markers include brain imaging used in conjunction with a specialized chemical that binds to beta-amyloid proteins. Amyloid is also present in cerebrospinal fluid, and can be detected by extracting and examining it. Compared to these procedures, the four trials may have discovered two that are relatively cheaper. 

"More research is needed in the very promising area of Alzheimer's biomarkers because early detection is essential for early intervention and prevention, when new treatments become available. For now, these four studies reported at AAIC point to possible methods of early detection in a research setting to choose study populations for clinical trials of Alzheimer's treatments and preventions," Snyder said.

How Smell Predicts Alzheimer's

As Alzheimer's plaques kill brain cells, they also destroy the cells needed for odor recognition. So it makes sense that having a worse sense of smell would predict cognitive impairment akin to Alzheimer's disease.

Two trials looked at how sense of smell is associated with Alzheimer’s progression. Both measured participants’ senses of smell and conducted interviews to measure cognitive performance. One of them also measured the size of certain parts of the brain, including the entorhinal cortex and hippocampus, which are associated with memory, as well as amyloid deposits in the brain. Both trials found that a worsening sense of smell as associated with Alzheimer’s progression. The study that looked at the size brain areas also found that elevated levels of amyloid in the brain might have thinned the entorhinal cortex.

The researchers cautioned that the results were preliminary, but were still hopeful. "If further large-scale studies reproduce these results, a relatively inexpensive test such as odor identification may be able to identify subjects at increased risk of dementia and Alzheimer's disease at a very early stage, and may be useful in identifying people at increased risk of cognitive decline more broadly," said Dr. Davangere Devanand, a professor of psychiatry at Columbia University Medical Center, in the release. 

Alzheimer's and the Eyes

It’s been suggested that people with Alzheimer’s develop beta-amyloid plaques in their retinas that are similar to the ones associated with Alzheimer’s.

The two studies that investigated how accurate eye imaging techniques were in identifying Alzheimer’s involved using either a supplement called curcumin, which turns amyloid fluorescent during imaging, or an ointment that binds to amyloid and is detectable with a laser scanner. Both showed over 80 percent accuracy in identifying Alzheimer’s, while also being able to determine who didn’t have it. Furthermore, one of them was also able to identify a 3.5 percent increase in retinal amyloid over a three month period, suggesting that the technique could be used to monitor responses to therapy.

"We envision this technology potentially as an initial screen that could complement what is currently used: brain PET imaging, MRI imaging, and clinical tests," said Shaun Frost, of the Commonwealth Scientific and Industrial Research Organization in Australia, in the release. "If further research shows that our initial findings are correct, it could potentially be delivered as part of an individual's regular eye check-up. The high resolution level of our images could also allow accurate monitoring of individual retinal plaques as a possible method to follow progression and response to therapy."

These trials were part of an initiative by the United States government, the Alzheimer's Association, and the Alzheimer's community, to prevent and effectively treat Alzheimer’s by 2025. 

Source: Frost S, Devanand D, Snyder H, et al. At The Alzheimer's Association International Conference 2014.