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Smell and Eye Tests Offer Potential for Predicting Alzheimer’s

Detecting signs of decline could help people pursue possible therapies earlier

Alzheimer eye test

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Both the nose and the eyes can serve as windows into what’s going on in the brain.

En español | In the search for easy-to-perform tests to predict Alzheimer’s disease risk, new research suggests the nose might know and the eyes might have it.

“Older patients are more and more often asking their doctors if they’re going to get Alzheimer’s disease,” William Kreisl, a Columbia University Medical Center neurologist, said at a briefing Tuesday at the Alzheimer’s Association International Conference (AAIC) in Toronto.

Detection of the disease before symptoms appear would enable people to make decisions about their care while they still can, said Melanie Campbell of the University of Waterloo in Ontario.

“We’re on the cusp of new therapies for Alzheimer’s disease,” so the earlier patients could begin taking them, the greater the chance they could work, added Suzanne Craft, an Alzheimer’s researcher at the Wake Forest School of Medicine.

Both the nose and the eyes can serve as windows into what’s going on in the brain. Researchers at the University of Pennsylvania have developed the University of Pennsylvania Smell Identification Test (UPSIT), an inexpensive scratch-and-sniff test that people can take on their own on in a doctor’s office. Low UPSIT scores have been shown to predict cognitive decline in people with no symptoms as well as in those with memory problems, Kreisl said.

The sense of smell is connected to areas of the brain affected early on in Alzheimer’s disease, he said. Kreisl and his colleagues compared UPSIT scores with beta-amyloid status in 84 adults who were age 68 on average. Beta-amyloid deposits are made of protein fragments, and their presence in the brain is a hallmark of Alzheimer’s disease.

The people in his study all took the UPSIT and underwent either a PET scan or a spinal tap. Those with an UPSIT score below 35 (out of 40) were three times more likely to have memory decline six months later than those with higher scores.

In a related study, other Columbia scientists administered UPSIT to 397 people, age 80 on average, who also underwent MRI brain scans. They found that people with low UPSIT scores were more likely to develop dementia during a follow-up period of four years. To a lesser degree, the MRI scans showed that thinning in the entorhinal cortex, the first part of the brain to be affected by Alzheimer’s, was also associated with a greater risk of developing dementia.

The eye might also prove to be an accessible avenue for assessing the status of amyloid in the brain, Campbell’s study found.

She and her collaborators examined the eyes of patients with and without Alzheimer’s who had donated their organs to science. Using polarizing microscopes, the researchers found amyloid deposits in the retinas of those who had Alzheimer’s. Polarization imaging of the eye is a promising tool for detecting amyloid deposits before Alzheimer’s symptoms appear, Campbell said.

Another promising imaging technology is optical coherence tomography, or OCT, which one study presented at the Alzheimer’s meeting used to assess amyloid in the retina, the light-sensitive tissue at the back of the eye.

Ophthalmologists regularly use OCT to diagnose diseases such as age-related macular degeneration, diabetic retinopathy and glaucoma.

Ophthalmologist Fang Ko and colleagues from the UCL Institute of Ophthalmology in London used OCT to study the connection between the retinal nerve fiber layer and performance on cognitive testing in 33,068 older individuals. Those with the thinnest layers did poorly on the greatest number of cognitive tests, Ko said at the briefing.

“Many older adults routinely visit their ophthalmologist, so incorporating this technology, once proven, into annual eye care visits could aid in assessing cognitive status and identifying individuals that should have further evaluation by a health-care professional,” Heather Snyder, director of medical and scientific operations at the Alzheimer’s Association, said in a news release.

In August 2017 researchers in California announced that they had conducted an imaging trial to detect retinal amyloid pathology in the eye, according to information published in JCI insight. 

"Our hope is that eventually the investigational eye scan will be used as a screening device to detect the disease early enough to intervene and change the course of the disorder with medications and lifestyle changes,” said Keith L. Black, coleader of the study and chair of the Cedars-Sinai Department of Neurosurgery, as reported by USA Today. 

The team of researchers plan to test their proof-of-concept in further clinical trials.