New ways to test for Alzheimers
Accurately diagnosing alzheimer’s is not an easy thing to do. In fact most of the time people aren’t diagnosed until very late in the progression of the disease, long after serious damage to the brain has been done. Biological markers of Alzheimer’s disease may be able to detect it at an earlier stage. For example, using brain 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. But as with anything that requires any sort of imaging techniques, these scans can be expensive and are not available everywhere. That is all about to change thanks to four new studies that aim to help offer multiple ways to test for alzheimers much earlier than we can currently test.
In two of the studies, the decreased ability to identify odors was significantly associated with loss of brain cell function and progression to Alzheimer’s disease. The other two studies showed that the level of beta-amyloid detected in the eye was significantly correlated with the burden of beta-amyloid in the brain and allowed researchers to accurately identify the people with Alzheimer’s in the studies.
[Loony hint: Beta-amyloid protein is the primary material found in the sticky brain “plaques” characteristic of Alzheimer’s disease. It is known to build up in the brain many years before typical Alzheimer’s symptoms of memory loss and other cognitive problems and once brain damage has occurred reversing it is nearly impossible.]
“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. For now, these four studies reported at AAIC point to possible methods of early detection in a research setting to choose study populations for clinical trials of Alzheimer’s treatments and preventions,” Snyder said..
There is growing evidence that the decreased ability to correctly identify odors is a predictor of cognitive impairment and an early clinical feature of Alzheimer’s. As the disease begins to kill brain cells, this often includes cells that are important to the sense of smell.
So researchers investigated the associations between sense of smell, memory performance, biomarkers of loss of brain cell function, and amyloid deposition in 215 clinically normal elderly individuals. The researchers administered the 40-item University of Pennsylvania Smell Identification Test [Or UPSIT for short and yes, it is a thing] along with 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 [parts of the brain which are important for memory] – and amyloid deposits in the brain.
In this study population, a smaller hippocampus and a thinner entorhinal cortex were associated with worse smell identification and worse memory. The scientists also found that, in a subgroup of study participants with elevated levels of amyloid in their brain, 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.
In a similar study, researchers investigated a multi-ethnic [34% White, 30% African-American, 36% Hispanic] sample of 1037 non-demented elderly people in New York City, with an average age of 80.7. The researchers then assessed them in a variety of ways at three time periods – from 2004-2006, 2006-2008, and 2008-2010. During the follow-up 109 people transitioned to dementia [101 Alzheimer’s]; it is sad but it should be mentioned that there were 270 deaths.
In 757 subjects who were followed, lower odor identification scores on UPSIT were significantly associated with the transition to dementia and Alzheimer’s disease. For each point lower that a person scored on the UPSIT, the risk of Alzheimer’s increased by about 10%. Further, lower baseline UPSIT scores, but not measures of verbal memory, were significantly associated with cognitive decline in participants 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.”
Recent studies have also identified beta-amyloid plaques in the retinas of people with Alzheimer’s – similar to those found in the brain – suggesting the possibility of simple, non-invasive methods of early detection.
Using that as a starting point, this study researchers reported preliminary results of volunteers who took a proprietary supplement containing curcumin, which binds to beta-amyloid with high affinity and has fluorescent properties that allow amyloid plaques to be detected in the eye using a novel system and a technique called retinal amyloid imaging [RAI]. Volunteers also underwent brain amyloid PET imaging to correlate the retina and brain amyloid accumulation.
However, preliminary results suggest that amyloid levels detected in the retina were significantly correlated with brain amyloid levels as shown by PET imaging. The retinal amyloid test also differentiated between Alzheimer’s and non-Alzheimer’s subjects with 100 percent sensitivity and 80.6 percent specificity.
Another study using a similar approach showed that used a novel 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; all participants’ Alzheimer’s status was masked from the observers.
The ointment was applied to the inside of participants’ 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.
Using results from the fluorescent imaging, researchers were able to differentiate people with Alzheimer’s from healthy controls 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.
“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.
I have to apologize for the length, but these four studies were talked about at Alzheimer’s Association International Conference 2014. It is not just exciting to think that we could detect alzheimer’s earlier, but also offer earlier treatment. This research could alter the way we view alzheimer’s and no longer have to worry about the pain and suffering it brings to families.
Nothing is worse than seeing the one you love be pulled away without any visible reason, especially in those few instances when they do remember.
Matthew E Growdon,, Aaron Schultz,, Alexander Dagley,, Rebecca Amariglio,, Trey Hedden,, Dorene M. Rentz,, Keith Johnson,, Reisa Sperling,, Mark W. Albers,, & Gad Marshall (2014).
Olfactory identification and Alzheimer’s disease biomarkers in clinically normal elderly Nature Neuroscience
Seonjoo Lee, New York State Psychiatric, Institute; Jennifer Manly, Columbia University Medical Center; Howard Andrews, Columbia University; Nicole, Schupf,, Adam M. Brickman,, Elan Louis,, Yaakov Stern,, & Richard Mayeux (2014). Olfactory identification deficits predict the transition from MCI to AD in a multi-ethnic community sample Nature Neuroscience
; Yogesan Kanagasingam, CSIRO; Lance Macaulay, CSIRO; Maya, Koronyo-Hamaoui, YOSEF KORONYO,, David Biggs,, Steven Verdooner, Keith Black,, Kevin Taddei,, Tejal Shah,, Stephanie Rainey,, Victor Villemagne,, Christopher Cleon Rowe,, & Ralph Martins (2014). Retinal amyloid fluorescence imaging predicts cerebral amyloid burden and Alzheimer’s disease
Charles Kerbage,, carl sadowsky,, Pierre Tariot,, Marc Agronin,, Gustavo Alva,, Darell Turner,, Dennis Nilan,, Anne Cameron,, & Gerald Cagle (2014). Detection of ligand bound to beta amyloid in the lenses of human eyes Nature Neuroscience