Smell and Eye Tests Offer Potential for Predicting Alzheimer’s

 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.

What’s the Best Way to Take an Afternoon Nap?

Settling in for a midday snooze has been given a bad rap. Getting caught napping is often code in the U.S. for being lazy. Yet many cultures build catnaps into their normal routines, and dozens of studies have shown that grabbing a few Zs in the daylight hours is healthy.

So what’s the best way to take a nap? One expert, David Dinges, the chief of the Division of Sleep and Chronobiology in Psychiatry at the University of Pennsylvania Perelman School of Medicine, explains how to optimize midday shut-eye.

Two Kinds of Naps

Dr. Dinges, who is also a member of the American Academy of Sleep Medicine, says that naps actually come in two forms: voluntary and involuntary. A voluntary nap, he says, is where a person makes a conscious decision to catch some relief before continuing her day.

“Those are naps that fill in additional sleep needs, and they have many health benefits,” he says. Involuntary naps, often the kind that happen when you’re caught napping, are considered to be a mark of someone who lacks the fortitude to stay awake. Dr. Dinges calls voluntary, or intentional, sleep the best way to fill up a person’s “sleep tank.”

“So if you live on a schedule where you only get six hours of sleep a night and you get 45 minutes of intentional naps a day, you don’t develop much of a sleep debt,” he says. Doctors recommend that adults get at least seven hours of sleep in a 24-hour period.

You’re Getting Sleepy…

Studies have shown that work hours and commute times are the two largest sources of sleep debt for Americans, Dr. Dinges says. This is why when sleep-deprived people get on the train or bus to commute home, they frequently doze off. The first sign of falling asleep is that the muscles relax. “First go the arms, then the hands, then the eyelids,” says Dr. Dinges, whose book, “Sleep and Alertness: Chronobiological, Behavioral and Medical Aspects of Napping,” dives deep into the science of siestas. “Next goes the neck, so your head falls over.”

That triggers the part of your brain that feels you’re falling, which wakes you up. These involuntary sleep attacks don’t provide much benefit, because “the brain doesn’t progress into sleep far enough for recovery, so it’s more like a disturbed night of sleep,” Dr. Dinges says. One way to prevent them is to drink caffeine, a natural stimulant that aids in alertness. The better way is to set yourself up for a proper, preventive nap.

A Window of Opportunity


Humans are biologically programmed to sleep at night, and to take a nap in the midafternoon, though scientists aren’t sure why. “There is no melatonin triggering the sleep, it just seems to be this harmonic phenomenon,” Dr. Dinges says. The consensus among his colleagues, he says, is that human civilization evolved mostly in equatorial climates, where it got very hot later in the day, and napping during the extreme heat optimized work performance.

To make the most of this biological need, don’t overthink it. Find a cool, dark, quiet place to lie down or put your head down. And put all your electronics away. The light from screens can mess with your ability to fall asleep.

A napper has to feel safe, which is why napping in public (or in a glass-walled office) is often less than ideal. “Set an alarm so you don’t oversleep” more than 15 to 60 minutes so as not to affect nighttime sleep. To alleviate the post-nap sleep inertia, have a cup of coffee.

Even a 15-minute nap is enough to relieve some sleep pressure, since the brain goes into light non-REM sleep, which contributes to recovery. “Being awake is like carrying a bag on your back. The longer you’re awake, the more bricks you add,” he says. “And when you take a nap, you remove some of those bricks.”