Tony Wyss-Coray, Ph.D., is an Associate Professor of Neurology at Stanford University and a Research Career Scientist at the Veterans Administration Palo Alto Health Care System.
The second day of the Breakthrough Ride was going to lead us from Santa Cruz to King City in the heart of Salinas Valley.
It was 5:25 am when the alarm went off and I had to pull my sore body out of bed. A hot shower helped a bit and I definitely felt better after a good breakfast at a Diner in Santa Cruz. My stack of pancakes was topped with a mountain of fresh strawberries and whipped cream and everybody seemed surprised that I managed to eat it all. But to be fair, we were just briefed that our ride today would be 99 miles!
The streets were still empty when we rolled out on this young Sunday morning and we were surprised to see the warm and sunny skies from yesterday afternoon replaced by coastal fog once again. Phil Jaeger came back from the wedding he attended last night for the ride ahead but Kurt and Bruce had left. Luckily, we were joined by our project manager Eric Goodwin, who, as we found out, coaches a cycling team in Chicago.
Off we went for day two, along the coast through Aptos, past Pajaro Dunes, and Watsonville. The scent of freshly turned soil merged into that of fresh cut cabbage and ripened strawberries – a tour de smell. At an intersection somewhere past Watsonville, we merged with a group of cyclers from the Monterey Velo Club and Eric was quick to advertise our ride. They were kind enough to let us ride in their draft to save some energy for the next five miles or so.
It had gotten warmer but there was still a layer of fog as we entered Salinas Valley, the birthplace of John Steinbeck. Around 10:30 the sun finally came out warming our muscles and producing an ever stronger tail wind up valley. There was no shade in this flat farming valley so we took refuge in the “Pony Cafe” for lunch. Ride staffers Melanie and Evan treated us with sandwiches and fruit and we even had iced coffees.
The wind was picking up and we were cruising behind Eric at an average speed of almost 20 mph over the next 40 miles on long agricultural roads. As we rode our steel horses (or carbon fiber…) into King City, tired from the strong wind and dusty roads, a huge tumble weed blew across the street just in front of us – what an amazing country. After a shower followed by a big steak, we were ready for bed.
Thank you to the whole Breakthrough Ride team for organizing such a breathtaking (pun intended) journey through the countryside. We are so privileged to be able to participate and I know this Ride will continue to inspire and sustain our dedication to research on Alzheimer’s disease.
And so it began...It was a cool (55 degrees) and foggy morning in San Francisco as myself (Bruce Lamb), Tony Wyss-Coray, Phillipp Jaeger and Kurt Lucin (all researchers at Stanford University) as well as Eric Goodwin (Manager of the Breakthrough Ride) gathered at 5:45 AM for our pre-ride breakfast. We were all nervous, excited and ready to get this ride going!
Upon arrival at the Marina Green Park Triangle, we saw the striking purple RV (nicknamed "The Pony") that will serve as our support vehicle for the entire ride across the country. Behind The Pony was the faint outline of the Golden Gate bridge that was shrouded in thick fog. We next met the Breakthrough Ride road crew, including manger, Joey, and staff Celeste, Evan and Melanie, the group that will support the ride all the way from Coast to Capital. In addition, we were joined by Harry Johns, the CEO of the Alzheimer's Association, who would be riding with us on this first day of the Breakthrough Ride. Upon receiving our daily briefing, we were ready to finally get underway!
After a brief ceremony, the countdown was on: 10, 9, 8, 7, 6, 5, 4, 3, 2, 1...GO! We jumped on our bikes and cautiously proceeded across the soft grassy knoll towards the road, as none of us wanted to fall in the first 50 yards of this trans-continental ride with cameras trained on our every move. It felt good to finally be riding and working towards our goal! I had attached the map of our route to my bike and was attempting to help direct us through the streets of San Francisco to get to Route 1, The Pacific Coast Highway. Despite my efforts we still had to back track from one wrong turn, but we were finally closing in on Route 1.
We reached the first major climb of the day. As we climbed, the fog became thicker and thicker, until finally visibility was reduced to less than a couple hundred feet. Our breathing became more labored and our hearts were now pounding. I called out to the other four team members, "Break!", and they answered "Through!", "Break!...Through!" "Break!...Through!" as we finally reached the top. It was a fun ride to the bottom, as Harry led the way, "pulling" the team along to the intersection with Route 1.
Soon after turning onto Route 1 (mile 15), we spotted The Pony sitting in a parking lot marking the first rest stop of the day. As we pulled in to the cheers of the road crew and support staff, we were all grateful to get some Gatorade, a snack, and a trip to the restroom. However, we were concerned about stopping too long, as the cool, damp weather was rapidly chilling our body temperatures. At this point, Harry Johns had to leave us for another engagement, but we continued on with the remaining four team members down Route 1 towards Half Moon Bay.
As we approached Half Moon Bay, the route took us to an all purpose trail that followed the shore. There were several creaky wooden bridges and beautiful blue and yellow wild flowers. While the fog by this point had partially lifted, we could still only imagine what the famous Northern California coastline looked like along the route. After a quick stop in Half Moon Bay and the departure of Phillip Jaeger, who was attending a wedding, Kurt, Tony and I continued on to our lunch stop at mile 45, which was at a beautiful beach along the shore. After a wonderful lunch of sandwiches, carrots, fruit and all the Gatorade you could drink we decided to continue on to the final push to Santa Cruz.
The last 35 miles of the day seemed a lot longer than the first 45, as our legs began to tire and our rear ends became increasingly sore. However, several events over this last stretch served as an inspiration and kept us working towards our goal. First, the fog finally cleared and we could now fully appreciate the breathtaking views as we passed along the jagged California coastline, although one had to be careful to keep your eyes on the road ahead! Second, a bicyclist approached us as we neared the top of a ridge and slowed to talk with us. "Hey," he said, "you are the guys riding for Alzheimer's disease, you're awesome. I read about you on Facebook!" Third, as we neared the final scheduled rest stop, we could see the purple Pony in the distance, but noticed a great commotion around the RV. As we got closer, we realized that the commotion was in fact the entire road crew dancing around the Pony in synchrony to their own silent soundtrack. We couldn't help but start to "hear" the same soundtrack and bounced along on our bikes for the last few miles of the day. Finally, we reflected on all of the incredible messages of support on the Breakthrough website, from individuals with Alzheimer's disease and their caregivers, which gave us great inspiration to complete the day's ride. We finally arrived in Santa Cruz at 3:15 PM and gave each other high fives as we celebrated the completion of the first day of the Alzheimer's Breakthrough Ride!
What an amazing day and beginning to the Alzheimer's Breakthrough Ride! I can't wait to follow this Blog as riders move across this great country!
Bruce T. Lamb, Ph.D., is an Associate Staff Scientist in the Department of Neurosciences at the Lerner Research Institute of the Cleveland Clinic, as well as Associate Professor in the Department of Molecular Medicine at the Cleveland Clinic Lerner College of Medicine and in the Departments of Neurosciences and Genetics at Case Western Reserve University. Dr. Lamb also is the Alzheimer’s Breakthrough RideSM Chair and is cycling to raise awareness and make Alzheimer’s disease a national priority. Beginning on July 17, Dr. Lamb and other Alzheimer’s disease researchers participating in the Alzheimer’s Breakthrough Ride will cycle cross-country segments, starting in San Francisco and ending in Washington, D.C. on World Alzheimer’s Day (September 21).
It was a warm, humid, Sunday morning last summer in Cleveland and I decided to go on my usual 30 mile bike ride through the Chagrin River valley. I had just returned from reviewing Alzheimer’s disease research grants for the National Institute on Health and felt increasingly perplexed and concerned regarding the declining funding for Alzheimer’s disease research through the National Institute on Aging (NIA). The percentile of Alzheimer’s disease grants funded through the NIA had dramatically dropped from 2008 to 2009, with further declines anticipated in 2010. Because of this, many Alzheimer’s disease research laboratories were forced to contract in size and some research labs were forced to close all together. Even worse, this meant that critical research that could provide new insights into disease mechanisms and potential therapies for the disease would not be conducted. Given the dramatically increasing incidence of Alzheimer’s disease from the 5.3 million people currently afflicted with the disease to the projected 13.5 million people with Alzheimer’s in 2050, certainly more research is required, not less.
As I started up the first major hill of the ride, my legs burned, my heart pounded and my head ached with indecision about what could be done to bring attention to this critical and unmet need. About half way up the hill, I wasn’t sure I would make it to the top. I finally stood up, slowed down, weaved my way from side to side and inched my way upwards through the steepest grades of the hill. As I reached the top, I realized that a different approach was needed to bring attention and funds to Alzheimer’s disease research, something that involved researchers from across the country united in their commitment to fighting the disease. While researchers frequently complain about funding rates, grant and manuscript reviews and bureaucratic roadblocks to conducting research, rarely do we make the time and effort to raise public awareness of research and advocate for increases in funding. Now is the time, I realized through my heavy, labored breathing, to step up and ride the extra mile and climb the next hill. What if Alzheimer’s researchers from across the country could unite and ride their bikes, from the west coast to the east coast through small towns and big cities, along the oceans and over mountains, reaching out to as many people as possible and finally arriving at the Capitol. Along the way, researchers could convince Americans of the vital role research must play in fighting Alzheimer’s disease. In addition, researchers would get signatures of individuals from across the country in support of increasing funds for Alzheimer’s disease research as proposed in the Alzheimer’s Breatkthrough Act that is currently before congress. It was something that had to be done.
Now, thanks to the involvement of some of the top researchers in the United States and strong organizational support form the Alzheimer’s Association, the Alzheimer’s Breakthrough Ride is a reality. The ride will be starting in July 17th in San Francisco, CA and continuing over 4,000 miles across the country and arriving in Washington, D.C. on September 21st, World Alzheimer’s Day. Today I ask for your support of this important initiative. Get involved, come out to greet and talk with the riders as they come through your community, sign the petition, contact your congressmen and senators and together let’s fight this disease! We have one hardest hill yet to climb and that is Capitol hill.
This week, nearly 4,000 scientists from around the world gathered to report and discuss the latest advances in research on treatments, risk factors, and diagnosis for the health epidemic of the 21st century – Alzheimer's disease – at the Alzheimer's Association's 2010 International Conference on Alzheimer's Disease (AAICAD 2010) in Honolulu.
"With an aging baby boomer generation, the Alzheimer's disease crisis will continue to touch more lives and create an unsustainable fiscal toll on the nation's healthcare system – particularly Medicare and Medicaid," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association.
"This week we saw promising investigations being pursued on a variety of fronts – avenues that could very well lead to significant changes in Alzheimer diagnosis and treatment. However, the chronic underinvestment in Alzheimer research continues to be the greatest obstacle to bringing new, more effective therapies to people," Thies said.
"Every day, researchers go to work with the sole purpose of advancing our understanding and knowledge about Alzheimer's, which is the defining disease of the baby boomer generation. We need a government response that shows equal commitment by providing the level of funding for research that will get us better diagnostic tests, treatments, and a cure," Thies added.
Highlights from the AAICAD 2010 included:
The Alzheimer's Association announced the launch of Alzheimer's Association TrialMatchTM, a confidential, free, and interactive tool that provides comprehensive clinical trial information and an individualized trial matching service for people with Alzheimer's disease and related dementias. The Internet (www.alz.org/trialmatch) and phone-based (800-272-3900) program provides a first-of-its-kind service in Alzheimer's by delivering individualized matches to clinical trials for people with Alzheimer's, their healthcare professionals, caregivers, and healthy volunteers.
The Dementia Demonstration Project (DDP), an interdisciplinary effort led by the Geriatric Research, Education and Clinic Center at the Minneapolis Veterans (VA) Medical Center, found that early detection, diagnosis and care management for people newly diagnosed with cognitive impairment and dementia can reduce outpatient costs by almost 30 percent. Veterans in the study who were diagnosed in the DDP clinics saw their average outpatient healthcare costs decline by an average of $1,991 in the year after diagnosis of cognitive impairment compared with the year before diagnosis. In the DDP clinics, following evaluation, the dementia care team met with the patient and family to review the results, discuss the diagnosis, and outline treatment recommendations. Informational material, assistance in identifying needed services, and direct support and training from team members was provided, as needed.
Evidence from three long-term, large-scale studies (Framingham Study, Cardiovascular Health Study, NHANES III) supports the association of physical activity and certain dietary elements (tea, vitamin D) with possibly maintaining cognitive ability and reducing dementia risk in older adults. Plus, a new study in an animal model of Alzheimer's reported today at AAICAD 2010 suggests that an antioxidant-rich diet with walnuts may benefit brain function. Research has pointed towards a number of factors that may impact our risk of Alzheimer's and cognitive decline, the strongest being reducing cardiovascular risk factors. The Alzheimer's Association and others have repeatedly called for longer-term, larger-scale research studies to clarify the roles that these factors play in the health of the aging brain. These studies from AAICAD 2010 are some of the first reports of this type in Alzheimer's, and that is encouraging, but it is not yet definitive evidence.
Scientists at AAICAD 2010 presented the first draft reports from three workgroups – covering Alzheimer's disease dementia, mild cognitive impairment (MCI) due to Alzheimer's disease, and preclinical Alzheimer's disease – convened by the National Institute on Aging (NIA) and the Alzheimer's Association to update the diagnostic criteria for Alzheimer's disease for the first time in 25 years. The proposals would change the existing criteria by better reflecting the various stages of the disease and the inclusion of Alzheimer's disease biomarkers. While the role of biomarkers differs in each of the three stages, much remains to be understood concerning their reliability and validity in diagnosis. This makes it critical that any new recommendations be thoroughly tested. Further input will be solicited by the NIA and the Association through a website launched immediately after the AAICAD presentations at www.alz.org/research/diagnostic_criteria.
The primary therapeutic target in Alzheimer's disease has been the beta amyloid peptide, which clusters outside cells in the brain to form sticky clumps known as plaques. Recently, more attention has been given to the tau protein, which aggregates inside the brain cells of people with Alzheimer's, forming neurofibrillary tangles. Four new, though very preliminary, research studies reported at AAICAD 2010 described experimental immunotherapies for Alzheimer's – two of which target tau directly and two of which may reduce tau even though their primary target was beta amyloid. Importantly, these studies teach us more not only about tau-targeted therapies but also about the progression of Alzheimer's disease. It may be that amyloid changes in the brain happen early in Alzheimer's, and tau-related changes happen "downstream" where they have a more direct effect on cognitive function. Thus, immunotherapy treatments targeting amyloid may also alter neurodegenerative processes that occur later in the disease. However, this is still to be determined.
In an early finding reported at AAICAD 2010, a gene known as FTO, which appears to be correlated with obesity in humans, may also increase risk of Alzheimer's disease and dementia. When a person has certain variants of both FTO and a recognized Alzheimer's risk gene known as APOE, the risk of Alzheimer's could be doubled. FTO has previously been shown to affect body mass index (BMI) and the risk for diabetes. These vascular risk factors have also been associated with risk of Alzheimer's disease. However, the researchers found that the increased risk was independent of these traits, suggesting that there is a different mechanism by which FTO is associated with an increased risk for Alzheimer's. We need to see these results confirmed by other researchers. In fact, we need to know more, in general, about the genetics and other causes of Alzheimer's so that we have additional targets for therapies and preventions.
Last minute scientific submissions to AAICAD 2010, known as "hot topics," suggested that (1) a newly-discovered risk gene for Alzheimer's may have early impact on memory skills and brain volume, (2) intranasal insulin may be beneficial in Alzheimer's, and (3) beta amyloid deposits in the brains of people with Alzheimer's disease may take different shapes based on a known Alzheimer's risk gene.
Two studies reported at AAICAD 2010 give us more information about the TOMM40 gene – a newly identified risk gene for Alzheimer's. They found that healthy, middle aged people who have the high risk version of TOMM40 (a) did worse on memory tests and (b) had reduced brain volume in two regions affected early in Alzheimer's.
A short-term (4 months) clinical trial of intranasal insulin in Alzheimer's and mild cognitive impairment (MCI) showed statistically significant benefits on certain tests of memory and functioning, but no changes on others. In those who showed benefits on memory tests, there were also positive changes in Alzheimer's biomarkers in spinal fluid. Larger, longer-term studies are planned.
Researchers using a new imaging tool suggest that there are different shapes of beta amyloid deposits in the Alzheimer brain based on which version a person has of a well-established Alzheimer's risk gene, known as APOE. This may be especially important because in some recent drug trials the therapy provided benefits in people who had certain types of APOE but were less effective or not effective in others.
Two new studies from AAICAD 2010 suggest that having Alzheimer's disease may increase the risk of getting other potentially disabling health conditions, including seizures and anemia. Researchers in one study found that that the rate of seizures, per 1,000 people per year, in a study population that included 14,838 people with Alzheimer's aged 50 years or older and 14,838 randomly-selected, age- and sex-matched people without Alzheimer's, was 9.1 among patients with Alzheimer's compared with 1.4 for those without Alzheimer's – an incidence rate that was 6.4 times higher. In a second study of 1,112 older adults (768 healthy controls, 133 MCI, 211 Alzheimer's), people with anemia were found to have an increased risk of Alzheimer's (odds ratio: 2.56). And people with Alzheimer's in the study were found to have an increased risk of being anemic (odds ratio: 2.61). If Alzheimer's also increases risk of other disabling conditions, then its impact may be more devastating than we've envisioned as the global population ages and as more countries become westernized in their habits and lifest
Racially and ethnically diverse older adults are one of the fastest growing population segments in the United States. New research presented AAICAD 2010 revealed that older African-Americans and Latinos with significant cognitive impairment have a lower likelihood of nursing home placement and longer survival than White older adults in the study. These results have significant implications for caregiver burden and community resources. There is a greater than anticipated need for culturally-appropriate dementia care resources and home and community- based services for these populations.
These findings are particularly compelling since African-Americans are about two times more likely and Latinos about one and one-half times more likely to develop Alzheimer's and dementia than Whites, according to the Alzheimer's Association's 2010 Alzheimer's Disease Facts and Figures report.
Another study reported at AAICAD 2010 suggests that the bereavement process and mourning experience for Alzheimer caregivers after the death of their loved one varies greatly among different racial and ethnic groups.
A third research report suggested that cultural and spiritual beliefs of African-Americans, American Indians and Whites greatly influence how long it takes for a family to seek a medical diagnosis of Alzheimer's.
-New Alzheimer's Risk Gene May Affect Memory Scores and Brain Atrophy in Middle Age -Clinical Trial of Intranasal Insulin Shows Benefits in Alzheimer's and MCI -Known Alzheimer's Risk Gene May Change Shape of Brain Deposits
Last minute scientific submissions to the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI, known as "hot topics," suggest that (1) a newly-discovered risk gene for Alzheimer's may have early impact on memory skills and brain volume, (2) intranasal insulin may be beneficial in Alzheimer's, and (3) beta amyloid deposits in the brains of people with Alzheimer's disease may take different shapes based on a known Alzheimer's risk gene.
Two studies reported at AAICAD 2010 give us more information about the TOMM40 gene – a newly identified risk gene for Alzheimer's. They found that healthy, middle aged people who have the high risk version of TOMM40 (a) did worse on memory tests and (b) had reduced brain volume in two regions affected early in Alzheimer's.
A short-term trial of intranasal insulin in Alzheimer's and MCI showed statistically significant benefits on certain tests of memory and functioning, but no changes on some others. In those who showed benefits on memory tests, there were also positive changes in Alzheimer's biomarkers in spinal fluid.
Researchers using a new imaging tool suggest that there are different shapes of beta amyloid deposits in the Alzheimer brain based on which version a person has of a well-established Alzheimer's risk gene, known as APOE. This may be especially important because in some recent drug trials the therapy provided benefits in people who had certain types of APOE but were less effective or not effective in others.
"These are some of the fantastic findings from this year's AAICAD, full of potential to move the field forward," said William Thies, PhD, Alzheimer's Association Chief Medical and Scientific Officer. "But there is too little happening in the field, and no plan in place from the federal government to stem the massive wave of Alzheimer's coming with the aging of the Baby Boomers."
"Alzheimer's is clearly the #1 public health challenge of the 21st century and research is the only way to solve this problem," Thies added. "There are more than 5 million Americans with the disease and about 11 million caregivers supporting them. Reliable estimates say that by 2050 those numbers could triple. Government must make an investment in Alzheimer research that proves they understand what's at stake – for individuals, families, the healthcare system, and the nation as a whole."
New Risk Gene for Alzheimer's is Associated with Poorer Memory Function and Grey Matter Loss in Middle Aged Persons Without Dementia
The TOMM40 gene has very recently been shown to influence age of onset in Alzheimer's disease. Two studies reported at AAICAD 2010 give us more information about this newly identified risk gene for Alzheimer's; they found that middle aged people without dementia who have the high risk version of the TOMM40 gene did worse on tests of memory and learning and had reduced brain volume in two regions that are often affected early in the course of Alzheimer's.
"These are exciting, initial results, but the exact role that TOMM40 plays in Alzheimer's remains to be determined," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "The story of TOMM40 is evolving and may give us new insights into Alzheimer's disease."
"We desperately need to know more about the causes of Alzheimer's, and the factors that affect our risk of getting or not getting the disease. This kind of research will provide more targets for therapies and prevention strategies," Thies said.
In one study, Mark Sager, MD, of the University of Wisconsin Medical School, and colleagues studied a total of 726 people in middle-age with a family history of Alzheimer's from the Wisconsin Registry for Alzheimer's Prevention who were genotyped for TOMM40 and APOE, the latter of which is a well-established risk gene for Alzheimer's. Of these, 129 had the low risk version of TOMM40 and 229 had the high risk version. The average age of the study population was 54.
The researchers found that the group with the high risk version of the TOMM40 gene performed significantly worse on the tests of learning and memory (Rey Auditory Verbal Learning Test) than the group with the low risk version. These results remained significant regardless of APOE gene type.
"The deficits shown by the high risk group are similar to the kinds of changes in memory and learning that are seen in very early Alzheimer's," Sager said. "In this study population, TOMM40 genotyping is allowing us to find evidence of very early Alzheimer's disease at least 20 years before people begin to show the outward symptoms. This is a step forward in Alzheimer's prevention research."
In a second study, Sterling Johnson, PhD, also of the University of Wisconsin School of Medicine and Public Health, and colleagues found that among healthy, middle aged adults (mean age 57) who have the APOE e3/e3 gene type, those with the high risk version of the TOMM40 gene had significantly less gray matter volume in two brain regions affected early in Alzheimer's disease than those with the low risk version of the gene.
According to the researchers, the study suggests that there is a connection between TOMM40 and brain cell loss in people who are relatively young and currently not symptomatic.
"This is the first study to associate TOMM40 to brain imaging in people at risk for Alzheimer's disease," Johnson said. "The brain differences between TOMM40 groups were very similar but less severe that what is observed in full-blown Alzheimer's. It may be that the TOMM40 gene will be a useful measure of Alzheimer's risk in middle-age, but additional research with longitudinal follow-up is needed."
Allen Roses, MD, and colleagues at Duke University first discovered that the TOMM40 gene helped explain differences in age of onset among people with sporadic Alzheimer's disease.
Clinical Trial of Intranasal Insulin Shows Some Benefits in Alzheimer's and MCI
Previous research has strongly suggested that Alzheimer's and diabetes/insulin resistance are closely related. For example, Alzheimer's is associated with reduced brain insulin signaling and low levels of insulin in cerebrospinal fluid (CSF).
"These deficiencies may reduce or eliminate insulin's beneficial roles in the brain," said Suzanne Craft, PhD, of VA Puget Sound Health Care System/University of Washington in Seattle. "We believe that restoring normal insulin function in the brain may provide therapeutic benefits to adults with Alzheimer's. Intranasal administration enables insulin to access brain regions that are compromised in Alzheimer's."
Craft and colleagues had previously shown enhanced cognition and daily functioning in adults with MCI and early Alzheimer's using intranasal insulin treatment for 21 days. This new study expanded the time frame to four months, during which 109 participants with MCI or Alzheimer's received either placebo, or 20 or 40 IU daily intranasal insulin treatment.
The researchers found that in the 20 IU dose group (10 IU twice daily) results on a test of delayed story recall significantly improved compared with those who received placebo, as did functional status measured by the Dementia Severity Rating Scale. Improvements in delayed memory recall persisted for two months after the insulin treatment ended. However, memory and learning on the ADAS-Cog and ability to do activities of daily living measured by the ADCS-ADL scores were unchanged.
For 15 of the insulin-treated participants who agreed to have a spinal tap, improved memory and functional status were associated with an improved Alzheimer's biomarker profile as reflected by a lowered CSF tau/Aβ42 ratio.
"These results provide encouraging support for further study of intranasal insulin as a therapy for Alzheimer's," Craft said. "We are currently planning a large, multi-center clinical trial."
New Imaging Compounds for Alzheimer's Protein Deposits in the Brain Show that Different Forms of the APOE Risk Gene Create Different Shapes of Beta Amyloid
A new class of biomarkers has been discovered that can stick to protein structures in the body and emit colors reflecting the different shapes or forms of the proteins. They are called luminescent conjugated oligothiophenes (LCOs) or luminescent conjugated polymers (LCPs). Among other uses, they are currently being employed in test tubes, animal models and autopsied Alzheimer's brains to study the structure of proteins deposits caused by the disease. The new markers bind to the two well-established hallmarks of Alzheimer's – beta amyloid plaques and tau tangles – and glow different colors depending on which forms of the deposits they "stick" to (e.g., plaques often "glow" orange, while tangles "glow" yellowish green).
In this study reported at AAICAD 2010, Sam Gandy, MD, PhD, of Mount Sinai School of Medicine, New York, and colleagues used LCOs/LCPs to investigate the possibility that the shape of brain protein deposits in people with Alzheimer's who have the APOE ε4/ε4 gene type (highest risk) is different from those having APOE ε3/ε3 (neutral risk).
Frozen brain sections from people who died with Alzheimer's were stained using two LCPs/LCOs: pentamer formyl thiophene acetic acid (pFTAA) and polythiophene acetic acid (PTAA). Using PTAA, the researchers observed that Alzheimer patients with APOE ε4/ε4 had core and cerebrovascular amyloid of different shapes, while in people with APOE ε3/ε3 the two amyloid structures had the same shape. Using pFTAA revealed that tau tangle densities in ε4/ε4 Alzheimer patients that were apparently greater than those with ε3/ε3.
"The findings support our hypothesis that APOE genotype changes amyloid structure," Gandy said. "This is important because the different shapes might respond differently to treatments that attempt to clear amyloid deposits from the brain."
In some recent drug trials, the experimental therapy provided benefits in people who had a certain type of the APOE gene (known as ε3) but were less or not effective in another type (ε4).
LCOs/LCPs were pioneered by Peter Nilsson of the Department of Chemistry, Linköping University, Sweden. The study also involved collaborating teams from Charité – Universitätsmedizin Berlin, Germany (led by Frank Heppner), Washington University, St Louis (led by David Holtzman), and other labs at Mount Sinai (led by Patrick Hof and Dara Dickstein).
Global Impact Could Multiply As The Population Continues to Age
Having Alzheimer's disease may increase the risk of getting other potentially disabling health conditions, including seizures and anemia, according to new research presented today at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI.
"Alzheimer's disease is a global health crisis with devastating effects on individuals, families, and national healthcare systems," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "If, in fact, Alzheimer's also increases risk of other disabling conditions, then its impact may be more devastating than we've envisioned as the global population ages and as more countries become westernized in their habits and lifestyles."
According to the 2009 World Alzheimer Report from Alzheimer's Disease International, a London-based nonprofit, international federation of 71 national Alzheimer organizations including the Alzheimer's Association, the number of people with Alzheimer's or another dementia, currently 35 million, is expected to nearly double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050.
Worldwide, the economic cost of dementia has been estimated as $315 billion annually. (Wimo, et al. "An Estimate of the Total Worldwide Societal Costs of Dementia in 2005." Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Vol. 3, Issue 2, April 2007.)
Alzheimer's is Associated with Increased Incidence of Seizures
Some small studies have shown Alzheimer's to be a risk factor for seizures. H. Michael Arrighi, PhD, of Janssen Alzheimer Immunotherapy Research & Development; Nicole Baker, MPH, Pfizer; and colleagues conducted an observational study to estimate the incidence rate of seizures among a large cohort of people with Alzheimer's. The researchers used anonymized electronic medical records from nearly 400 primary medical practices in the United Kingdom. The study population included 14,838 people with Alzheimer's aged 50 years or older and a comparison cohort of 14,838 randomly-selected, age- and sex-matched patients without Alzheimer's. People with Alzheimer's were followed for an average of 2.3 years; non-Alzheimer's patients were followed for an average of 3.4 years.
Over that time period, the researchers found that the rate of seizures, per 1,000 people per year, was 9.1 among patients with Alzheimer's disease compared with 1.4 for those without Alzheimer's – an incidence rate that was 6.4 times higher. In addition, they found that the incidence rate of seizures was highest among the youngest Alzheimer's patients, and that it decreased with age. Incidence among non-Alzheimer's patients increased slightly with age.
"The increased risk of seizures among patients with Alzheimer's disease was seen in all age groups, but there was a substantial increase among the youngest patients. It is especially important for these patients and their caregivers to be aware of this risk," Baker said.
"The connection between Alzheimer's and seizures provides additional avenues for research into the basic biology of both diseases, and possibly interventions and therapies to respond to the overall impact of Alzheimer's disease" Arrighi said.
Alzheimer's is Associated with Lower Hemoglobin Levels and Anemia
Studies suggest that iron accumulates in the tau tangles in the brains of people with Alzheimer's, and that overall levels of iron are elevated in both Alzheimer's and Mild Cognitive Impairment (MCI) brains. However, it is not clear from the scientific literature if this altered brain iron profile is reflected in plasma iron levels.
Noel Faux, PhD, of the Mental Health Research Institute, Parkville, Australia, and colleagues examined hemoglobin, iron and other blood-based measurements in the 1,112 participants (768 healthy controls, 133 MCI, 211 Alzheimer's) of the Australian Imaging Biomarkers and Lifestyle (AIBL) study of Ageing. Participants also completed questionnaires on diet and medication intake (including supplements). Results were then correlated with measures of short-term, long-term and total memory, and global cognition.
The researchers found that people with Alzheimer's in the study had significantly lower levels of hemoglobin, mean cell hemoglobin concentration (MCHC), and packed cell volume compared with healthy controls, after adjustment for age and gender. Consistent with these data, the erythrocyte sedimentation rate (ESR) was significantly higher in Alzheimer's compared to healthy controls.
Participants with anemia in the study were found to have an increased risk of Alzheimer's (odds ratio: 2.56). And people with Alzheimer's in the study were found to have an increased risk of being anemic (odds ratio: 2.61). Self reported iron intake was not different in the two groups.
"In our population, we found that people with Alzheimer's disease were more likely to be anemic, and this was not explained by dietary iron deficiency," Faux said. "This suggests that hemoglobin production is deficient in Alzheimer's patients."
"Alzheimer's had not previously been recognized as a risk factor for anemia, which is a common clinical problem for the elderly and can contribute to problems such as heart failure and renal failure," Faux continued. "The cause of anemia in Alzheimer's is still uncertain, but we speculate that Alzheimer's is a disease that affects both brain and blood. We are currently investigating this intriguing possibility."
- When Combined with a Known Alzheimer's Gene, Your Alzheimer's Risk may be Doubled -
A gene known as FTO, which appears to be correlated with obesity in humans, may also increase risk of Alzheimer's disease and dementia, according to new research presented today at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI. And when a person has certain variants of both FTO and a recognized Alzheimer's risk gene known as APOE, the risk of Alzheimer's could be doubled.
"While scientists know Alzheimer's involves progressive brain cell failure, they have not yet identified any single reason why cells fail," said Maria Carrillo, PhD, senior director of Medical and Scientific Relations at the Alzheimer's Association. "However, there is evidence about certain factors that may increase the likelihood of developing Alzheimer's."
"Some of these factors we can't control, such as age, family history, and genetics," Carrillo said. "Others we may be able to influence, including heart health, tobacco and alcohol use, and head injury."
FTO has previously been shown to affect body mass index (BMI), leptin levels (a protein hormone that plays a key role in appetite and metabolism), and the risk for diabetes. These vascular risk factors have also been associated with risk of Alzheimer's disease.
In the study reported at AAICAD 2010, Caroline Graff, MD, PhD, and colleagues at the Karolinska Institutet, Sweden, explored the direct role of the FTO gene on Alzheimer's and dementia risk in old age. In addition, a possible interaction of FTO with the APOE gene, a well-established genetic risk factor for Alzheimer's, was assessed. The researchers followed 1,003 people aged 75 years and older without dementia from the Kungsholmen project, Sweden, for nine years to detect new cases of Alzheimer's and dementia. All participants had been genotyped for FTO and APOE on DNA sampled at the beginning of the study.
They found that people in the study population who carried the AA gene-variant in the FTO gene had a 58 percent increased risk for developing Alzheimer's and a 48 percent increased risk for developing dementia compared with those who did not have this genetic variant, after adjustment for age, gender, education, and APOE genotype.
The findings also suggest that the risk-effect of FTO-AA on dementia is further elevated to 100 percent increased risk in the presence of APOE ε4, which is the highest risk variant of the APOE gene. The effect of the FTO-AA genotype on Alzheimer's and dementia risk remained after additional adjustment for diabetes, BMI, cardiovascular disease and physical inactivity.
"One of the intriguing aspects of the results is that the increased risk was independent of the traits previously associated with FTO, such as obesity and diabetes measured at baseline," Graff said. "Our results suggest that the mechanism by which FTO is associated with an increased risk for Alzheimer's and dementia may be different from how it increases the risk for obesity."
"This is a fascinating early finding, which fits with the known connections between heart health and brain health," Carrillo said. "However we do need to see these results confirmed by other researchers. In fact, we desperately need to know more, in general, about the genetics and other causes of Alzheimer's so that we have additional targets for therapies and preventions. One major positive step in that direction would be for the federal government to address its chronic underfunding of Alzheimer's disease research."
The Alzheimer's Association announced today the launch of Alzheimer's Association TrialMatch™, a confidential and free interactive tool that provides comprehensive clinical trial information and an individualized trial matching service for people with Alzheimer's disease and related dementias. The Internet (www.alz.org/trialmatch) and phone-based (800-272-3900) service debuted during the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu, HI.
There are as many as 5.3 million Americans living with the Alzheimer's and every 70 seconds someone in America develops the disease, according to the Association's 2010 Alzheimer's Disease Facts and Figures. This year, there will be one half million new cases of Alzheimer's; in 2050, there will be nearly a million new cases annually.
"Alzheimer's disease is clearly the #1 public health challenge of the 21st century and research is the only way to solve this problem," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association.
Recruiting and retaining trial participants is one of the greatest obstacles to developing the next generation of Alzheimer's treatments, perhaps second only to lack of funding.
"If patients are not enrolling in trials, there can be no advances in diagnosis, treatment and prevention, making the lack of study participants a significant public health issue," Thies said. "Alzheimer's Association TrialMatch provides a first-of-its-kind service in Alzheimer's by delivering a user-friendly and individualized guide to clinical trials for people with Alzheimer's, their healthcare professionals, caregivers and healthy volunteers."
More than 100 clinical studies in Alzheimer's and dementia are currently taking place and dozens more experimental compounds are moving from the laboratory to clinical testing. For people with Alzheimer's and their caregivers, clinical trials present an opportunity to play a more active role in their own treatment – ultimately contributing to scientific discovery and benefiting future generations.
About Alzheimer's Association TrialMatch Alzheimer's Association TrialMatch is designed to be easy to use for people with Alzheimer's, with web and phone support, specially trained staff, and tools developed with input from people with Alzheimer's.
The strength of this Web- and national 800 line-based service is that Alzheimer's Association TrialMatch contains a comprehensive, constantly updated database of institutional review board-approved Alzheimer's, mild cognitive impairment and other dementia trials taking place across the U.S. Specialists at the Alzheimer's Association's national Helpline – available 24-hours a day – assist in the process of matching individuals to clinical trials for which they are eligible based on study inclusion/exclusion criteria, diagnosis, treatment history and location.
By Association policy, telephone specialists will not recommend any particular clinical trial, but will describe all studies for which the person is eligible. They will answer questions about the trial process and connect individuals with trial sites based on their unique profile. Patients and caregivers will be encouraged to share their trial matches with their healthcare professionals to help decide whether a clinical trial is appropriate.
"We're looking to physicians to play a leadership role in referring their patients to Alzheimer's clinical trials and to Alzheimer's Association TrialMatch," said Marilyn Albert, PhD, Professor of Neurology at Johns Hopkins and Director of their Division of Cognitive Neuroscience. "As healthcare professionals, there is more we can do to help our Alzheimer's patients post-diagnosis by offering access to potential cutting-edge research and treatments being tested."
Alzheimer's Association TrialMatch can be accessed at www.alz.org/trialmatch or by calling toll-free, (800) 272-3900.
The technology and platform for Alzheimer's Association TrialMatch is provided by EmergingMed.
A new website showcasing the latest in Alzheimer's disease research and science - www.alz.org/research - is being unveiled at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) in Honolulu.
The website, called the Alzheimer's Association "Research Center," presents an extensive portfolio of information designed for a public searching for more knowledge about the current state of Alzheimer research, including both the latest news from the global research effort and how to volunteer for local Alzheimer's clinical trials.
Equally attractive to scientists and medical researchers, the site will also host valuable information that they can use, including highlights from Alzheimer's and Dementia: The Journal of the Alzheimer's Association, and information about scientific grants available from the Association.
"As I travel the country and talk to people whose families are affected by Alzheimer's disease, and as I read my daily e-mails, it is strikingly apparent that a wide range of people are genuinely interested in learning about what's happening in Alzheimer's science and when the next breakthroughs are going to come," said Angela Geiger, Chief Strategy Officer at the Alzheimer's Association. "The Alzheimer's Association is exploring innovative ways to advance research and also to engage and educate all kinds of people. This new website is an extension of this ever-expanding effort."
The innovative website seamlessly combines rich visuals with easy-to-understand content on a broad array of topics including:
* What Alzheimer's is, and how the disease progresses. * Advances in treatments, diagnosis and prevention. * How to volunteer for Alzheimer's clinical trials. * Updates on key local, national and global research initiatives.
Important concepts about Alzheimer's the disease are explained and illustrated. Leading scientists are profiled. All of this and more is found at the "Research Center" in an easy-to-navigate presentation that enables users to quickly discover and connect with the information that matters most to them. Regular updates will include new information, interviews, graphics, and videos.
"Research is the most critical aspect of solving the Alzheimer crisis. This is why it is vital to have a place where people can go to find out about the latest Alzheimer research," Geiger said. "We listened to our constituents who said they wanted to know, learn and understand more. We hope this site serves as a catalyst for deeper understanding about Alzheimer research and a long-term dialogue with the public that encourages hope and engages them in the Alzheimer's cause."
It’s a busy time in Washington. In addition to health care reform, Congress is busy finishing the Appropriations bills in both the House and the Senate.
We want to make sure the bills include funding for Alzheimer’s disease research at the National Institutes of Heath (NIH) and funding for the Healthy Brain Initiative at the Centers for Disease Control (CDC).
PTSD ASSOCIATED WITH HIGHER ALZHEIMER’S/DEMENTIA RISK; MODERATE ALCOHOL CONSUMPTION MAY LOWER IT
PTSD ASSOCIATED WITH HIGHER ALZHEIMER’S/DEMENTIA RISK; MODERATE ALCOHOL CONSUMPTION MAY LOWER IT
Also, Survey Shows Adults Don’t Know Heart Risk & Alzheimer’s Risk Are Related
Vienna, July 13, 2009 – Though discoveries about Alzheimer’s disease risk factors are often in the news, adults do not know about the relationship between Alzheimer’s disease risk and heart health, nor that physical activity can be protective against dementia, according to new research reported today at the Alzheimer’s Association 2009 International Conference on Alzheimer’s Disease (ICAD 2009) in Vienna.
Two additional studies reported at ICAD 2009 show higher Alzheimer’s risk in veterans with post-traumatic stress disorder (PTSD), and lower Alzheimer’s risk among adults who consume moderate amounts of alcohol.
“Your brain plays a critical role in almost everything you do: thinking, feeling, remembering, working, and playing – even sleeping,” said Maria Carrillo, PhD, Director of Medical & Scientific Relations at the Alzheimer’s Association. “The good news is that we now know there’s a lot you can do to help keep your brain healthier as you age. These steps might also reduce your risk of developing Alzheimer’s disease or another dementia.”
“There’s a strong and credible association between heart health and brain health. If people learn about and do some simple lifestyle modifications, such as being more physically active and eating a brain healthy diet, it could have an enormous impact on our nation's public health and the cost of healthcare,” Carrillo added.
The studies reported at ICAD 2009 were: -- Colleen Jackson, et al – Dementia literacy: Public understanding of known risk factors. -- Kristine Yaffe, et al -- Post-traumatic stress disorder and risk of dementia among U.S. veterans. -- Kaycee M Sink, et al - Moderate alcohol intake is associated with lower dementia incidence: results from the Ginkgo Evaluation of Memory Study (GEMS).
Dr. William Thies discusses studies presented during the first day of the 2009 Alzheimer's Association International Conference on Alzheimer's Disease.
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The following op-ed was published in the Charleston Gazette, Charleston, WV, on March 26, 2008 By Jane Marks
On March 18, the Alzheimer's Association released its latest collection of relevant data about all aspects of the disease and its impact, current and future, on this country. It is a devastating portrait of a looming public health epidemic, and includes this sobering fact: 10 million Baby Boomers will likely get Alzheimer's disease.
Because this developing health crisis is not being addressed by our national policymakers, the association also took out full-page ads in three national newspapers to ask the three major presidential candidates, Sens. Hillary Clinton, John McCain and Barack Obama, what they plan to do about Alzheimer's.
Alzheimer's is a degenerative disease that kills the brain and eventually the person, and at this time, there are no effective treatments to stop its progression. Today, there are 78 million Baby Boomers who are going to start turning 65 in less than three years. We're staring into the face of an epidemic but we're ignoring it:
There are about 5 million Americans living with the disease and by midcentury, that number is expected to increase to as many as 16 million.
In West Virginia, we have approximately 47,000 individuals with Alzheimer's.
Every 71 seconds, someone in this country develops Alzheimer's and by 2050, the rate will be every 33 seconds.
Today, there are between 200,000 to 500,000 people under age 65 with young-onset Alzheimer's disease or other dementias.
Experts predict that by 2010, there will be almost a half-million new cases of Alzheimer's disease each year; and by 2050, there will be almost a million new cases per year.
The resulting growth in spending on Medicare and Medicaid will threaten the viability of these already-stressed public programs. We do not have the health infrastructure to support or care for the rising number of people with Alzheimer's.
We can change these facts, but not with the current proposed federal research budget that underfunds medical research. Researchers are close to finding effective treatments that can slow the progression of the disease, but they are not getting funds they need. For the past five years, the NIH budget has been essentially flat. Compared to medical research inflation, NIH has actually lost 13 percent in purchasing power. The number of grants has declined significantly over this period; young researchers are leaving the field.
New and effective treatments for Alzheimer's will not only save millions of Americans and their families from tragedy and threat to retirement security, but Medicare and Medicaid could yield savings of $60 billion annually if we find these treatments. NIH underfunding is a trend that cannot continue with the next presidential administration and Congress. There is too much at stake. At this time, there is no national policy or strategy in place to deal with this 21st century public health threat. As the presidential campaign focus comes to West Virginia, I hope you will join me in asking Sens. Clinton, McCain and Obama: If you are agents of change, you need to alter the course of Alzheimer's disease and make it a thing of the past. What is your plan?
Marks is the executive director of the Alzheimer's Association's West Virginia chapter. She can be reached at jane.marks@alz.org
The Alzheimer’s Association is the leading voluntary health organization in Alzheimer care, support and research.
Our mission is to eliminate Alzheimer's disease through the advancement of research; to provide and enhance care and support for all affected; and to reduce the risk of dementia through the promotion of brain health.
Alzheimer's Association National Office, 225 N. Michigan Ave., Fl. 17, Chicago, IL 60601-7633
Alzheimer's Association is a not-for-profit 501(c)(3) organization
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