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.
Scientists at the Alzheimer's Association International Conference on Alzheimer's Disease 2010 (AAICAD 2010) today presented the first draft reports from three workgroups 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 current criteria for the diagnosis of Alzheimer's were established by a National Institute of Neurological Disorders and Stroke (NINDS)/Alzheimer's Disease and Related Disorders Association (ADRDA) workgroup in 1984. These criteria were almost universally adopted and have been useful; they have survived intact without modification for more than 25 years. However, experts note, the field has evolved to a great extent since then.
"Important scientific discoveries have been made in Alzheimer's, and there have been significant changes in our knowledge and conception of the disease," said Creighton H. Phelps, Ph.D., Director of the Alzheimer's Disease Centers Program, Division of Neuroscience, National Institute on Aging at the National Institutes of Health. "The NIA and the Alzheimer's Association, after consultation with the Alzheimer's scientific and medical community, concluded that the diagnostic criteria may need to be revised to incorporate scientific advances. We decided to convene workgroups to examine the literature and make recommendations."
At AAICAD 2010, leaders of the three workgroups – which covered Alzheimer's disease dementia, mild cognitive impairment (MCI) due to Alzheimer's disease, and preclinical Alzheimer's disease – presented preliminary reports at a special session for initial comment by the Alzheimer's community.
"The proposals would change the 1984 criteria by better reflecting the various stages of the disease and the inclusion of Alzheimer's disease biomarkers," said William Thies, PhD, Chief Medical and Scientific Officer at the Alzheimer's Association. "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 we thoroughly test any new recommendations."
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. After that input is incorporated, next steps are publication in a peer-reviewed journal followed by systematic validation through incorporation of the criteria into clinical trials.
"The proposed criteria for Alzheimer's disease dementia must be flexible enough to eventually be used – once they are validated – by both general health care providers without access to neuropsychological testing, advanced imaging, and CSF measures, as well as specialized investigators involved in research or clinical trial studies with access to these measures," said Guy McKhann, MD, of John Hopkins University School of Medicine, who chaired this workgroup.
The Importance of Moving to Earlier Diagnosis
Alzheimer's is thought to begin years, perhaps even decades, before symptoms are noticeable. But there is no single, generally accepted way to identify the disease in its earliest stages – before symptoms are evident.
According to Phelps, earlier detection of people at highest risk for Alzheimer's and those who have the earliest forms of the disease will facilitate finding the right individuals to participate in risk reduction and prevention research studies.
"The NIA and the Alzheimer's Association hope this process of updating and revising the Alzheimer's diagnostic criteria with modern technologies and the latest advances will provide standards that move the field further in the direction of early detection and treatment," Thies said. Significant Advances in Alzheimer Research Since 1984
Among the most important advances in the Alzheimer's field since the publication of the 1984 NINDS/ADRDA diagnostic criteria are:
Alzheimer's-driven changes in the brain, as well as the accompanying cognitive deficits, develop slowly over many years with dementia representing the end stage of years of pathology accumulation. At the same time, we know that some people have the brain changes associated with Alzheimer's and yet don't show symptoms of dementia.
Predictive genes in early onset Alzheimer's indicate that the initial events ultimately leading to both clinical symptoms and pathological brain changes begin with disordered beta amyloid metabolism.
The e4 allele of the APOE gene is well accepted as a major genetic risk factor for late onset Alzheimer's disease, which is defined as onset at 65 or older.
Biomarkers for Alzheimer's have been developed and are being validated. These fall into several categories:
Biomarkers of beta amyloid pathology, including amyloid PET imaging and levels of beta amyloid in cerebrospinal fluid (CSF).
Biomarkers of neuronal injury, including levels of CSF tau and phospho-tau.
Biomarkers of neuronal dysfunction, including decreased uptake of FDG on PET scans.
Biomarkers of neurodegeneration, including brain atrophy on structural MRI scans.
In addition, it has been only in the past decade that a better understanding of the distinctions and overlaps of Alzheimer's with non-Alzheimer's dementias has begun to emerge. Knowledge of the non-Alzheimer's dementias was rudimentary in 1984, and the current diagnostic criteria are vague in defining distinctions between Alzheimer's and the major alternatives. The common co-existence of Alzheimer's and cerebrovascular disease is now appreciated. Much more is known about dementia resulting from Lewy Body disease, and also about Pick's disease and other frontotemporal dementias.
Three Work Group Reports Present New Ideas for Research Criteria and Better Define Early Stages of Alzheimer's Disease
The NIA/Alzheimer's Association working groups were organized around the three stages of Alzheimer's disease that are commonly thought to exist today – pre-clinical Alzheimer's, mild cognitive impairment (MCI) due to Alzheimer's, and Alzheimer's dementia.
Pre-clinical – The group is laying out a research agenda to identify methods of assessment that may help predict risk for developing the disease. Biomarkers and other clinical assessment tools to identify early cognitive decline are being investigated to establish the presence of Alzheimer's brain changes in people with no overt symptoms and to identify those who may eventually develop the disease.
Mild cognitive impairment – The group is refining the MCI criteria, which will help to indicate cognitive change before dementia and better differentiate MCI from Alzheimer's. Research is underway to better understand the cognitive changes taking place, how they may relate to biomarkers, and which of these methods best indicate the likelihood of imminent progression to Alzheimer's dementia.
Alzheimer's dementia – The group is revising the existing criteria for diagnosing Alzheimer's to include possible biomarkers and other assessments that may aid in diagnosis.
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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