A decreased ability to identify odors, as well as eye examinations, could help diagnose Alzheimer’s disease earlier, according to the results of four research trials reported at the Alzheimer’s Association International Conference 2014 in Copenhagen.
In two of the studies, less ability to identify odors was significantly associated with loss of brain cell function and the progression to Alzheimer’s disease. In the other two studies, the level of beta-amyloid detected in the eye allowed researchers to accurately identify the people with Alzheimer’s in the studies.
Beta-amyloid protein is the primary material found in the sticky brain “plaques” characteristic of Alzheimer’s disease, according to officials with the Alzheimer’s Association. It is known to build up in the brain many years before typical symptoms of memory loss and other cognitive problems appear.
“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 Heather Snyder, Ph.D., Alzheimer’s Association director of medical and scientific operations.
“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.”
At this time it is only possible to detect Alzheimer’s late in its development, when significant brain damage has already occurred, researchers note. Biological markers may be able to detect it at an earlier stage.
Testing for Alzheimer’s with Smell
For example, using brain positron emission tomography (PET) imaging in conjunction with a specialized chemical that binds to beta-amyloid protein, the buildup of the protein as plaques in the brain can be revealed years before symptoms appear, according to researchers. But these scans can be expensive and are not available everywhere.
Amyloid can also be detected in cerebrospinal fluid through a lumbar puncture, researchers noted.
In response to growing evidence that a declining ability to identify odors is an early sign of Alzheimer’s, researchers at Harvard University investigated the associations between the sense of smell, memory, biomarkers of loss of brain cell function, and amyloid deposits in 215 healthy elderly individuals enrolled in the Harvard Aging Brain Study at Massachusetts General Hospital.
The researchers administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT) and a comprehensive battery of cognitive tests. They also measured the size of two brain structures deep in the temporal lobes — the entorhinal cortex and the hippocampus (which are important for memory) — and amyloid deposits in the brain.
The researchers found that a smaller hippocampus and a thinner entorhinal cortex were associated with worse smell identification and worse memory, reported Matthew E. Growdon, B.A., M.D./M.P.H. candidate at Harvard Medical School and Harvard School of Public Health.
The scientists also found that, in a subgroup of study participants with elevated levels of amyloid in their brains, greater brain cell death, as indicated by a thinner entorhinal cortex, was significantly associated with worse olfactory function after adjusting for variables including age, gender, and an estimate of cognitive reserve.
“Our research suggests that there may be a role for smell identification testing in clinically normal, older individuals who are at risk for Alzheimer’s disease,” said Growdon.
“For example, it may prove useful to identify proper candidates for more expensive or invasive tests. Our findings are promising but must be interpreted with caution. These results reflect a snapshot in time. Research conducted over time will give us a better idea of the utility of olfactory testing for early detection of Alzheimer’s.”
In another study, a research team led by Davangere Devanand, M.B.B.S., M.D., a professor of psychiatry at Columbia University Medical Center, investigated a multi-ethnic group of elderly people in New York City, with an average age of 80.7, who did not have dementia.
They were assessed in a variety of ways at three time periods — from 2004-2006, 2006-2008, and 2008-2010. UPSIT was administered in English and Spanish between 2004 and 2006. During follow-up, the researchers found that 109 people transitioned to dementia, included 101 who developed Alzheimer’s. There were 270 deaths.
Devanand reported that, in 757 subjects who were followed, lower odor identification scores on UPSIT were significantly associated with the transition to dementia and Alzheimer’s disease, after controlling for demographic, cognitive, and functional measures, language of administration, and apolipoprotein E genotype. For each point lower that a person scored on the UPSIT, the risk of Alzheimer’s increased by about 10 percent, the researchers found.
Lower baseline UPSIT scores also were significantly associated with cognitive decline in those people without baseline cognitive impairment.
“Odor identification deficits were associated with the transition to dementia and Alzheimer’s disease, and with cognitive decline in cognitively intact participants, in our community sample. The test was effective in both English and Spanish,” said Devanand.
“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.”
Testing for Alzheimer’s with the Eye
Recent studies also have identified beta-amyloid plaques in the retinas of people with Alzheimer’s — similar to those found in the brain — suggesting another possible method of early detection.
At the Alzheimer’s conference, Shaun Frost of the Commonwealth Scientific and Industrial Research Organization (CSIRO) in Australia reported the preliminary results of a study of volunteers who took a proprietary supplement containing curcumin, which binds to beta-amyloid.
It has fluorescent properties that allow amyloid plaques to be detected in the eye using a new system from NeuroVision Imaging, and a technique called retinal amyloid imaging (RAI). Volunteers also underwent brain amyloid PET imaging to correlate the retina and brain amyloid accumulation.
“An abstract prepared for the conference gives the results for 40 participants out of the 200 in the study. The full study is expected to be completed later this year,” the researchers said.
Preliminary results suggest that amyloid levels detected in the retina were significantly correlated with brain amyloid levels. The retinal amyloid test also differentiated between Alzheimer’s and non-Alzheimer’s subjects with 100 percent sensitivity and 80.6 percent specificity, the researchers reported.
Additionally, studies on an initial cohort showed an average 3.5 percent increase in retinal amyloid over three and a half months. This could be a means for monitoring a patient’s response to therapy, according to the researchers.
“We envision this technology potentially as an initial screen that could complement what is currently used: Brain PET imaging, MRI imaging, and clinical tests,” Frost said.
“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.”
Finally, Paul D. Hartung, M.S, president and CEO of Cognoptix, reported the results of a study of a fluorescent ligand eye scanning (FLES) system that detects beta-amyloid in the lens of the eye using a topically-applied ointment that binds to amyloid and a laser scanner.
The researchers studied 20 people with probable Alzheimer’s disease, including mild cases, and 20 age-matched healthy volunteers.
The ointment was applied to the inside of each person’s lower eyelids the day before measurement. Laser scanning detected beta-amyloid in the eye by the presence of a specific fluorescent signature. Brain amyloid positron emission tomography (PET) scanning was performed on all participants to estimate amyloid plaque density in the brain, the researchers noted.
Using results from the fluorescent imaging, researchers were able to differentiate people with Alzheimer’s from healthy people with high sensitivity (85 percent) and specificity (95 percent). In addition, amyloid levels based on the eye lens test correlated significantly with results obtained through PET brain imaging, according to the researchers. They add that no serious adverse events were reported.
“There is a critical need for a fast, dependable, low-cost and readily available test for the early diagnosis and management of Alzheimer’s disease,” said Pierre N. Tariot, M.D., director of the Banner Alzheimer’s Institute in Phoenix, and a principal investigator in the study.
“The results of this small Phase 2 feasibility study validate our previously reported results and demonstrate the ability of the FLES system to reproduce the findings of clinical diagnosis of Alzheimer’s with high sensitivity and specificity,” said Hartung. “This system shows promise as a technique for early detection and monitoring of the disease.”
Source: The Alzheimer’s Association