100 years ago: The birth of Alzheimer science
The year 2006 marked the 100th anniversary of a small medical meeting in Tübingen, Germany, where physician Alois Alzheimer presented the haunting case of Auguste D.
Alzheimer first saw Auguste in 1901, following her admission at age 51 to the psychiatric hospital where he worked. She was plagued by symptoms that did not fit any known diagnosis: rapidly failing memory, confusion, disorientation, trouble expressing her thoughts, and unfounded suspicions about her family and the hospital staff.
Auguste died after four years of steady decline that left her bedridden and mute, and Alzheimer performed an autopsy. In her brain, he found dramatic shrinkage, widespread dead and dying cells, and two kinds of microscopic deposits he’d never seen before.
“All in all,” Alzheimer wrote in his presentation abstract, “we are faced obviously with a peculiar disease process.”
This mysterious, devastating disorder soon entered the medical literature as “Alzheimer’s disease.” The unusual brain deposits gained recognition as its pathological hallmarks and became known as “plaques” and “tangles.”
In 1915, Alois Alzheimer himself died at age 51, never suspecting that his encounter with Auguste D. would one day touch the lives of millions, drive a massive international research effort, and set the cornerstone for the Alzheimer’s Association vision: A world without Alzheimer’s disease.
100 years later: The Alzheimer’s Association International Conference on Alzheimer’s Disease and Related Disorders (ICAD)
If Alois Alzheimer had new observations to share with colleagues in 2006, chances are good he would present them at the Alzheimer’s Association 10th International Conference on Alzheimer’s Disease and Related Disorders (ICAD). The July event attracted more than 5,000 scientists, breaking previous attendance records and solidifying its position as the premier global event in dementia research and treatment.
Over five days in Madrid, more than 2,100 scientific sessions offered state-of-the-art insights into the basic biology of dementia, strategies to translate new knowledge into targets for next-generation therapies, and latest findings on the emerging field of prevention. ICAD coverage in print, online and broadcast news generated more than 142 million media impressions worldwide, raising awareness of Alzheimer’s and highlighting the Association’s pivotal role in supporting the science that will solve the mystery of this devastating disease.
Headline-generating ICAD news included several reports strengthening the connection between insulin resistance, Type 2 diabetes, and dementia.
One study found borderline diabetes increases dementia risk almost 70 percent. Another concluded that among Type 2 diabetics, those with the poorest blood sugar control have the greatest dementia risk. And several preliminary reports hinted that the thiazolidinediones (TZDs) might help treat Alzheimer’s disease or prevent it from developing. TZDs, which include pioglitazone and rosiglitazone, are Type 2 diabetes drugs that help the body’s cells respond to insulin more effectively. This improved insulin response, in turn, aids better use of blood sugar to fuel essential cellular work.
To provide more robust evidence about the possible benefit of TZDs, GlaxoSmithKline in 2006 launched a large Phase III clinical trial of extended-release rosiglitazone in combination with cholinesterase inhibitors as a treatment for mild-to-moderate Alzheimer’s disease.
The Alzheimer’s Association 2006 grant portfolio includes an award to ICAD opening plenary speaker Monique Breteler, M.D., Ph.D., to help clarify the relationship between metabolic syndrome, insulin resistance, and cognitive health. Breteler, an internationally renowned epidemiologist, will explore these issues as part of the Rotterdam Study, which has been collecting biochemical, genetic, and autopsy data on more than 8,000 volunteers since 1990.
In another attention-grabbing ICAD session, Harvard scientist Lee Goldstein, M.D., Ph.D., reported that changes in the lens of the eye detectable by a brief, non-invasive laser pulse might reliably indicate the earliest stages of beta-amyloid buildup. The chief substance in the plaques originally identified by Alois Alzheimer, beta-amyloid has emerged as a prime suspect in brain cell destruction. Ability to monitor levels could provide a better way to monitor disease progression and response to beta-amyloid-targeting drugs.
Goldstein’s ICAD report earned him an invitation to appear as a keynote speaker at the 14,000-member Optical Society of America’s October 2006 annual meeting. His work is supported by the Alzheimer’s Association through the generosity of Rally for Research.
Also closely watched was an ICAD report on a new strategy for administering rivastigmine (Exelon) via a skin patch. Rivastigmine is a cholinesterase inhibitor now approved by the U.S. Food and Drug Administration (FDA) in pill form to treat mild to moderate Alzheimer’s disease.
The ICAD study showed the skin patch offered participants with moderate Alzheimer’s disease greater benefit than a placebo in memory, ability to carry out daily activities, and overall function. In addition, more than 70 percent of study caregivers preferred the skin patch over the currently available pill. The patch was also less likely to cause nausea and vomiting, common side effects in this class of drugs.
More younger individuals than expected have Alzheimer’s
The June 2006 Alzheimer’s Association report Early Onset Dementia: A National Challenge, A Future Crisis suggests Auguste D. was far from alone in having Alzheimer’s disease in her 50s.
Based on data from the Health and Retirement Study (HRS), a large, nationally representative survey, and findings from several other studies, the Alzheimer’s Association estimates there are between 220,000 and 640,000 Americans age 55 to 64 with early onset Alzheimer’s and other dementias. Additional research is needed to develop a more exact figure, but this evidence-based first estimate indicates many more Americans are affected by dementia in late middle age than is generally acknowledged.
Younger individuals with Alzheimer’s face special challenges, such as difficulty getting an accurate diagnosis because the cause of their symptoms is so unexpected; coping with how their symptoms and diagnosis affect their jobs and families, which often include children still living at home; and inadequate services and support, since most of these programs are geared to older adults.
To better understand these challenges, the Alzheimer’s Association in 2006 convened a new advisory group of early onset individuals. Their input will help us better understand their experience, and develop strategies and programs to meet their unique needs.
The early-onset report was released at the Alzheimer’s Association Annual Public Policy Forum in June 2006.
Progress in next-generation treatments
Alois Alzheimer had nothing to offer Auguste D. in terms of specific medical treatments or specialized care. The year 2006 was the 10th anniversary of FDA approval of donepezil (Aricept), the mainstay of drugs specifically approved to treat Alzheimer symptoms. Donepezil is now one of five approved Alzheimer drugs, and progress is accelerating in developing and testing additional treatments that may be able to delay or stop the progression of underlying disease processes.
To help fuel this progress, the Alzheimer’s Association Research Roundtable in 2006 hosted two face-to-face meetings where members and invited guests convened to address important issues in drug discovery and development. The April meeting explored the most promising experimental treatment approaches aimed at targets other than beta-amyloid, and the November event focused on cognitive health economics and the real-world value of dementia treatments.
Results of the face-to-face meetings are disseminated to the larger science community in papers appearing in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. Our journal celebrated its first full year of publication in 2006.
To ensure that promising treatments become available as quickly as possible, Alzheimer’s Association senior management and science and policy staff met with then acting FDA Commissioner Andrew von Eschenbach to discuss strategies to facilitate expedient review of investigational Alzheimer drugs.
In response to Association requests, the FDA established an Intra-Agency Neurology Working Group to better address new products to diagnose and treat Alzheimer’s and other neurological disorders. The FDA also agreed to appoint to the appropriate panels both an individual with Alzheimer’s disease and a caregiver to broaden the review process to reflect their unique perspecti
Caregiver support improves life, delays nursing home care, saves money
Auguste D. was not happy to be a patient in the psychiatric hospital where Alois Alzheimer became her doctor. Like others with Alzheimer’s, she would have preferred to stay at home. Many caregivers also prefer to keep their loved ones home as long as possible: A 2006 study by Mary Mittelman, M.D., Dr. P. H., suggests one successful strategy to maximize time at home.
Mittelman found that intensive, proactive counseling for people caring for a spouse with Alzheimer’s disease improved coping skills, and reduced stress levels and likelihood of developing depression. On average, the counseling delayed the need for nursing home care by 18 months, translating to an average savings of about $90,000 for each family. This study was supported in part by an Alzheimer’s Association grant, through the generosity of the Zenith Fellows.
Although this study dramatically demonstrates the power of appropriate support and services, most individuals with Alzheimer’s eventually need more day-to-day assistance than families can provide. With its multi-year Campaign for Quality Residential Care, the Alzheimer’s Association has taken the lead in developing evidence-based, consensus-driven standards to make life in nursing homes and assisted living as good as possible.
In September 2006, the Association released Phase 2 of its Dementia Care Practice Guidelines detailing best practices in preventing falls, avoiding use of restraints, and protecting residents from wandering. The Phase 2 practice guidelines were announced at the 14th Annual Alzheimer’s Association Dementia Care Conference, the premier educational event for professional care providers.
Taking another giant step for quality care, the Alzheimer’s Association in June launched CareFinderä, an online resource that takes users through a step-by-step personalized assessment to help them identify the best care options to meet their individual needs.
Alzheimer’s Association awards its largest grant portfolio
To sustain the momentum driving recent progress in Alzheimer research, treatment and care, the Alzheimer’s Association in July 2006 announced its largest research grant portfolio ever. Awards included about $21 million to 96 projects ranked highest in a field of 644 applicants in a rigorous peer-review process.
The 2006 portfolio also included the Association’s largest single grant in its history: a $2.1 million award to add a study arm focusing on positron emission tomography (PET) scans using Pittsburgh compound B (PIB) to the Alzheimer’s Disease Neuroimaging Initiative (ADNI). ADNI is a multi-year effort to standardize brain imaging procedures and to determine whether imaging or laboratory tests can offer improved strategies to diagnose Alzheimer’s and monitor response to experimental treatments.
As always, key goals of the Alzheimer’s Association research program are to move the field forward and help shape the science agenda; sustain a robust pipeline of novel ideas; and provide funds to attract talented young investigators to dementia research.
Federal funding slips drastically
The Alzheimer’s Association is a passionate advocate for sufficient federal funding to meet the critical public health challenge posed by Alzheimer’s disease. According to new data from the National Center for Health Statistics, Alzheimer’s disease is now the seventh leading cause of death in America.
In February 2006, President George W. Bush proposed a budget representing the largest cuts in federal spending for Alzheimer research and programs in the history of the Alzheimer’s Association. Congress adjourned on December 9 without agreeing on a final budget. As a result, funding continues flat at 2006 levels until Congress again addresses the budget issue in February 2007.
The inability of Congress to complete the budget is deeply disappointing in light of recent progress in Alzheimer science. Severe health and economic consequences face our nation if we fail to meet the challenge of Alzheimer’s disease.
A report in the April 22, 2006 Lancet dramatically demonstrates the short-sightedness of giving medical research short shrift in our national priorities. The study, one of the first to systematically analyze the health and economic impact of publicly funded research, found the 10-year return on investment in clinical trial funding was 4,600 percent.
New discoveries emerging from just eight of these trials were responsible for an estimated additional 470,000 healthy years of life. The study analyzed research funded by the National Institute of Neurological Disorders and Stroke, one of the U.S. National Institutes of Health (NIH).
Moving forward
Progress in 2006 continued at the same rapid pace we have seen over the last 15 years, and the Alzheimer’s Association intends to use every means at its disposal to ensure that we sustain that pace. Although we have learned a great deal about Alzheimer’s disease, there is still much we don’t know. But one thing is certain: One hundred years is long enough.
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