Imagine a simple eye exam or blood test revealing early stages of Alzheimer’s, and that these tests can be performed at your optometrist’s and general practitioner’s offices. They’d replace traditional ways of testing for the disease, which include a spinal tap or a brain scan. That’s one goal that may become a reality.
Scientists are hoping to find reliable, affordable, and easy-to-use diagnostics for detecting Alzheimer’s at its earliest stages. Following are a look at some of the promising studies:
Our eyes provide a window into our brains
Doctors at Duke Eye Center at Duke University Hospital looked into the eyes of more than 200 people and found that the loss of blood vessels in the retina could signal Alzheimer’s disease. Those with healthy brains showed microscopic blood vessels formed a dense web at the back of the eye inside the retina and those with Alzheimer’s had a less dense and even sparse web of blood vessels. The research was published in the March 11 issue of Ophthalmology Retina.
“The eye is a very unique organ since it is optically clear,” said Dilraj S. Grewal, a Duke ophthalmologist and retinal surgeon and lead author on the study. “This permits direct imaging of the back layer of the eye called the retina. It’s an extension of the brain.”
Blood vessels that can’t be seen during a regular eye exam were measured using a new noninvasive technology that takes high-resolution images of very small blood vessels within the retina in just a few minutes, making it possible to detect any changes in cognition. This new technology is called optical coherence tomography angiography (OCTA). OCTA machines use light waves that reveal blood flow in every layer of the retina.
All of the patients in this study were older than 50 years of age. “We did control for age and gender when analyzing the differences among the two (healthy brains and brains with Alzheimer’s) groups,” Grewal said. “However, with this relatively small dataset (39 people in the study had Alzheimer’s), we cannot accurately determine differences among men and women within the groups. This is one of several questions we hope to answer in the second phase of our study when we start to collect data again this fall.”
A much larger dataset, Grewal explained, would determine differences between the groups on a larger range of parameters. “This is just the beginning. The technology holds promise for other neurodegenerative disease as well, both for diagnosis and for monitoring progression and predicting response to potential therapeutic interventions. Before it’s ready for prime time use in the general public, this is going to take several years — hopefully in the next decade.”
Intervening early
“Years before people exhibit the more obvious memory deficits associated with Alzheimer’s diagnoses, the ability to learn new rules and associations become rigid as people lose the ability to flexibly apply what they have learned to novel situations, even though they can still recall previously learned facts and events,” said Mark Gluck, a professor at Rutgers University’s Center for Molecular and Behavioral Neuroscience department.
Gluck and a colleague devised the Rutgers Generalization Tasks, two innovative cognitive assessments sensitive enough to identify generalization deficits with patients showing the earliest signs of Alzheimer’s-related symptoms. Their assessments revealed deficits before they’re apparent on standard memory tests.
Most recently, he teamed up with John Ringman of USC Alzheimer’s Disease Research Center in Los Angeles. Together they took Gluck’s research a step further by working with a different population: people who have a family history of the disease and carry the Alzheimer’s gene but are asymptomatic.
“These individuals are essentially certain to develop the disease,” Gluck said. “We compared preclinical individuals carrying Autosomal Dominant Alzheimer’s Disease (ADAD) genetic mutations to non-carrying kin. And as we predicted, preclinical ADAD mutation carriers made significantly more errors during generalization tests than non-carrying kin.”
Their findings were published in the journal Neurobiology of Aging.
Disparities in rates of Alzheimer’s among African Americans
We all know that exercise improves health. However, this study found a gene that reduces the benefit of exercise in preventing Alzheimer’s for African Americans.
Gluck of Rutgers co-authored this study published in Frontiers in Aging Neuroscience and found, “The presence of a risk variant of the ABCA7 gene appears to diminish the ability of physical fitness to increase cognition and memory abilities in older African Americans, thereby indirectly increasing their risk for Alzheimer’s disease. This may be an important contributing factor to the disparities in rates of Alzheimer’s among African Americans.”
Gluck and his team studied 100 healthy African Americans from Newark, N.J., ages 55 to 86. The group included 20 men and 80 women. Some in the group carried the non-risk gene variant, while others carried the higher-risk variant. Those with the non-risk gene benefitted from exercise by showing fewer cognitive errors than those with the higher-risk gene.
According to Gluck, these findings could lead to a deeper understanding of the unique pathways to Alzheimer’s disease that put African Americans at higher risk, and thus point us towards new approaches to therapeutic or behavioral changes that could reduce the burden of Alzheimer’s on African Americans.
Diagnostics accelerator
Bill and Melinda Gates and Jeff and MacKenzie Bezos invested in a new fund with the Alzheimer’s Drug Discovery Foundation called Diagnostics Accelerator, a research program that aims to fast-track the development of diagnostic tools and biomarkers for Alzheimer’s disease and related dementias. The fund recently announced the first round of awards. Recipients include:
- Saliha Moussaoui, Ph.D., Amoneta Diagnostics SAS, France, is developing a rapid non-invasive diagnostic test to predict mild cognitive impairment and early Alzheimer’s disease by measuring two species of ribonucleic acids that are stable in the blood and show promise in early detection of Alzheimer’s disease.
- Kaj Blennow, M.D., Ph.D, at the University of Gothenburg, Sweden, is creating the first ultra-sensitive blood test for brain specific tau; these are fragments in the cerebral spinal fluid that correlate with Alzheimer’s disease neuropathology and will now extend this approach into the blood.
- Tom MacGillivray, Ph.D., University of Edinburgh, Scotland, is focusing on a combination of retinal biomarkers capturing neurodegeneration and vasculature dysfunction often found in Alzheimer’s disease with advanced imaging analyses. MacGillivray hopes the results will create widespread use of a cloud-based system for analyzing retinal images or incorporated into the eye scan device software.
- Peter Van Wijngaarden, Ph.D., Centre for Eye Research in Australia, will test a simplified eye scan, which can detect amyloid in the retina prior to signs of cognitive decline. His team is developing a more portable and inexpensive prototype camera that he hopes will replace the expensive PET imaging or invasive CSF tests for Alzheimer’s diagnosis.
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