With Alzheimer's disease spreading fast among the world's aging population, researchers are increasingly focused on the search for new ways to detect and treat the brain-killing disease in its earliest stages.
In two separate studies on the connection between dementia and sense of smell, teams of researchers found that a decreased ability to detect odors in older people, as determined by a common scratch-and-sniff test, could point to brain cell loss and the onset of dementia.
In two other studies, researchers showed that noninvasive eye exams also might offer a way to identify Alzheimer's in its early stages.
The findings - which are to be presented Sunday at the Alzheimer's Association International Conference in Copenhagen, Denmark - raise hopes that doctors could develop simple, inexpensive diagnostic tools that would hunt down reliable biomarkers of a disease that affects more than 5 million people in the United States.
Alzheimer's is a progressive and incurable disease that begins in areas of the brain associated with memory. It is the leading cause of dementia in older people, usually striking after the age of 65. It robs people of their cognitive abilities, speech and, ultimately, their identities. Eventually, it shuts down the most basic body functions, resulting in death.
The studies to be released Sunday are just a few of those that will be discussed at the six-day Alzheimer's Association conference, which has grown since the nonprofit first organized the event in 1988 in Las Vegas. The conference, which became annual in 2009, brings together thousands of researchers from more than 60 countries to discuss the latest developments in detecting and treating the disease.
The four studies to be released Sunday were united in their search for easily detectable biomarkers for Alzheimer's.
Scientists have long suspected a link between a person's ability to detect odors and the slow destruction of brain cells caused by Alzheimer's disease, particularly in the disease's early stages.
In one trial, researchers led by Reisa Sperling in the Harvard Aging Brain Study focused on 215 clinically normal people who had no complaint of memory loss and were living in their communities. They were given the University of Pennsylvania Smell Identification Test, a packet of scratch-and-sniff panels with 40 different odors.
The participants then underwent more exhaustive mental and physical evaluation, including annual cognitive evaluations; genetic analysis of known risk factors; and brain scans using MRI's and positron emission tomography (PET).
The PET scans used an injected substance to determine the level of beta-amyloid protein deposits inside each participant's brain. Clumps of beta-amyloid fragments, which are a distinguishing characteristic of Alzheimer's, form plaques between brain cells and are thought to kill them.
The MRI scans measured each subject's entorhinal cortex, which is located in the brain's medial temporal lobe near the hippocampus and plays a role in processing smell and forming short-term memories. It is also one of the first regions of the brain affected by Alzheimer's.
What the researchers found was that people who performed poorly on the odor-identification and memory tests also showed elevated levels of beta amyloid proteins in their brains, as shown in PET scans and other tests. Their entorhinal cortexes were also thinner, which is associated with poorer memory.
“It's an intriguing finding,” said Matthew Growdon, a fifth-year student in a joint program between Harvard Medical School and the Harvard School of Public Health. Growdon, who analyzed the data, said the results suggest a significant correlation between performance on the simple scratch-and-sniff tests and more established and costly markers of Alzheimer's detected by diagnostic tools such as the MRI or PET scan.
But Growdon also cautioned about reading too much into the findings. People's sense of smell can deteriorate for any number of reasons besides Alzheimer's, ranging from Parkinson's to allergies, he said. He also emphasized that the test involved only a small sample of people at one point in time; it is only the beginning of a study intended to follow the testing subjects over several years. What's more, the results have not yet been submitted to a medical journal or undergone peer review beyond the conference.
But Growdon, in an interview, said the research offers hope that the odor-detection test might someday be used with other diagnostic tools to help identify people at risk of Alzheimer's.
“We envision a future where we can predict risk and then do things to lower risk,” he said.
In a similar study, Davangere Devanand, a professor of psychiatry at Columbia University Medical Center, and colleagues administered the same University of Pennsylvania odor-detection test on 1,037 healthy, elderly people several times over a longer period of time.
His team also found some correlation between declining sense of smell and the transition from mild cognitive impairment to dementia: Of those who took part, 757 people who scored lower on tests of their sense of smell also showed a decline from mild cognitive impairment to dementia and Alzheimer's.
On a separate track, two groups of researchers investigated a possible link between levels of beta-amyloid in the eye - as detected by a new, relatively inexpensive imaging technology - and levels of the same protein in the brain, as seen through PET scans.
A group at the Commonwealth Scientific and Industrial Research Organization in Australia administered an eye scan to 200 test subjects using technology from California-based NeuroVision Imaging to see whether levels of beta-amyloid in the eye would correlate to levels in the brain as determined through brain scans.
The subjects were given a substance containing curcumin, which binds to beta-amyloid and appears fluorescent in certain conditions, and underwent eye exams. Then they underwent PET scans of the brain. Preliminary findings involving 40 subjects discovered a correlation between beta-amyloid levels in the eye and inside the brain.
In a separate trial, Pierre Tariot, director of Phoenix-based Banner Alzheimer's Institute, and Paul Hartung, the head of Cognoptix, conducted tests using a laser scanner and an ointment applied to the eye and also found a link between levels of beta amyloid in the eye's lens and inside the brain.
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