Smell tests cannot distinguish between Alzheimer's disease and other disorders
Retina tests reveal the presence of amyloid plaque, a signature symptom of dementia
Alzheimer’s researchers are looking to our noses and our eyes for early signs of disease.
Two studies presented Tuesday at the Alzheimer’s Association International Conference 2016 suggested that older adults with worsening ability to identify odors might be on the road to cognitive decline. Two other presentations explored different types of eye tests as possible predictors of the disease.
Alzheimer’s is the most common type of dementia, causing problems with memory, thinking and behavior.
According to Heather Snyder, director of medical and scientific operations of the Alzheimer’s Association, these four studies represent “a positive step forward to earlier detection and intervention.”
Catching a health problem sooner rather than later can help prevent the worst from happening in many cases. Yet diagnosing Alzheimer’s in the earliest stages is not easy. Some symptoms, such as failing memory, may be hard to distinguish from the usual signs of old age, while other signs, such as confusion, may appear only after significant brain damage has occurred.
One abnormal structure in the brain is believed to be a driver of the disease: toxic amyloid plaque, which accumulates in the brain. Years before a patient shows Alzheimer’s symptoms, PET scans can reveal plaque in the brain, while spinal taps can show plaque in cerebrospinal fluid.
Unfortunately, PET scans are expensive, and lumbar punctures can cause pain. Doctors would much prefer a low-cost, noninvasive test that would diagnose Alzheimer’s at an early stage.
According to Snyder, such a test could lead to dramatic improvements in early detection and management of the disease.
The nose knows
In the race to find such a test, two separate teams of Columbia University researchers presented work based on the 40-item University of Pennsylvania Smell Identification Test, or UPSIT. Seonjoo Lee, an assistant professor of clinical biostatistics, and her colleagues enlisted the help of 397 nondemented people at an average age of 80.
Lee gave all the participants brain scans and UPSIT tests and then followed them over four years. During that time, 49 people developed Alzheimer’s disease, while nearly one in five of the participants showed signs of weakening mental function.
Lee discovered that participants who scored lower on the odor test at the beginning of the study were more likely to be among those who showed mental decline later. Participants whose scans showed a thinning in the brain area that plays a role in memory – the first brain region affected by Alzheimer’s – were more likely to develop Alzheimer’s.
In a second unrelated Columbia study, Dr. William Kreisl, an assistant professor of neurology, examined smell scores in combination with brain scans and cerebrospinal fluid for 84 participants with the beginning signs of weakening memory and 26 healthy participants. At six months, 67% of participants showed memory decline.
Analyzing the data, the researchers discovered that signs of plaque in either the brain scan or spinal fluid predicted decline while smell test scores did not. Still, participants with an UPSIT score of less than 35 were three times more likely to decline than those with a score greater than 35. Though more research is needed, Kreisl said in a statement, “odor identification testing may prove to be a useful tool in helping physicians counsel patients who are concerned about their risk of memory loss.”
This idea has been around for a long time, with “innumerable” studies showing how odor identification may modestly predict the progression from either normal or mild cognitive impairment to a worse level of function, said Dr. David Knopman, a neurologist at the Mayo Clinic.
“The problem is that the accuracy of odor identification is just not good enough to be a standalone test,” said Knopman, who is not affiliated with either study. Another problem: “Olfactory disorders” are not specific to Alzheimer’s disease, he said. For example, patients with Lewy body dementia also score low on UPSIT, and so a “smell test” would not be able to distinguish between the two types of patients.
Seeing is believing
Another idea researchers around the world have studied in relation to Alzheimer’s disease is retinal thickness. In fresh research, Dr. Fang Ko of the UCL Institute of Ophthalmology in London explored the thickness of the retinal nerve fiber layer as a possible predictor of memory loss and other mental failings. Thickness of this layer is known to decrease with age.
For the study, Ko and his colleagues conducted eye tests, physical exams, cognitive tests and surveys of 33,068 participants. Ko found a significant link between thinner layers and poor cognition. In fact, participants with a low test score on any one cognitive test had thinner retinal nerve fiber layers.
According to Dr. Samuel E. Gandy, a professor of neurology and psychiatry at the Icahn School of Medicine at Mount Sinai Hospital, “reports like these appear every few months, but none have held up to careful scrutiny.” Unfortunately, the findings are never “robust or reproducible,” said Gandy, who is not affiliated with any of these studies.
In a separate eye study, Melanie Campbell, a professor of physics at University of Waterloo, and her colleagues focused on detecting amyloid protein deposits in the retina. Since the eye is a window to the brain, the research team analyzed diseased eyes of 20 humans and six dogs, alongside 22 healthy human retinas and seven healthy dog retinas.
“We looked at the eyes of both deceased people and animals and live animals,” Campbell explained. “We had two major outcomes.” First, the research team confirmed that amyloid can be seen in the retinas of animals and people with Alzheimer’s. Importantly, the amyloid deposits were seen before cognitive impairment began, so they begin to appear in the retina early in the disease.
The second outcome: Campbell verified that her polarization technique – in which optics measure light reflected off deposits of amyloid in the eye – is equally sensitive when used with or without dye. This is key to being able to perform the test on living people.
“Our results suggest that this could become an early, noninvasive test for Alzheimer’s disease,” she said.
“Maybe these are the breakthroughs, but the smart money would bet on caveat emptor,” Gandy said, adding that he “would not make much” of eye tests until large numbers of people with appropriate age-matched controls had been studied by several independent groups.
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However, Knopman said he believes this second retinal study is interesting “because if amyloid can be imaged in the eye, it might be far simpler than doing a PET scan.” Plaque is a “more direct” connection to Alzheimer’s disease than a smell test, he said.
If the results hold up after more extensive experiments, this simple eye test may become the go-to test for accurately diagnosing Alzheimer’s in patients long before symptoms appear.