"Developing Topics" At AAIC 2013 Show Cutting Edge Brain Imaging Techniques, Reveal Problems With Screening And Misdiagnosis

- No evidence found to support general population dementia screening -

- Misdiagnosis of Alzheimer's leads to excess costs -

- Encouraging first reports for tau imaging in Alzheimer's -

BOSTON, July 17, 2013 /PRNewswire-USNewswire/ -- Results from four research studies reported at the Alzheimer's Association International Conference® 2013 (AAIC® 2013) in Boston range from a review of population-level studies to a single case history, demonstrating the scope of research being pursued by Alzheimer's researchers around the world.

The four studies were presented as "developing topics" at AAIC 2013, which often include last-minute calculations and data analyses. They include:

• A systematic review showed no evidence that screening for dementia in the general population had any effect on patient outcomes. The researchers caution policymakers not to adopt population-based dementia screening without a clear sense of risks and benefits.
• A random sample of Medicare recipients with vascular dementia and Parkinson's disease — who had all been previously misdiagnosed with Alzheimer's — showed that the misdiagnosis led to significant excess costs compared with people who had not been misdiagnosed. Costs decreased quickly after proper diagnosis.
• A PET scan imaging agent known as [11C]PBB3, which shows the tau protein that forms the Alzheimer's "tangles" — one of the two hallmark brain lesions of the disease — showed promising results in a preliminary study of Alzheimer's patients and healthy controls.
• The potential effectiveness of another tau imaging agent, [F-18]-T808, was indicated in the first autopsy examination of a single subject. Brain tissue samples showed evidence of tau in the same areas and amounts as suggested by the imaging drug in the person's PET scan.

"These studies vividly demonstrate the necessity of taking a variety of approaches to effectively diagnosing, treating and preventing Alzheimer's disease," said Maria Carrillo, Ph.D., Alzheimer's Association vice president of medical and scientific affairs. "The Alzheimer's Association takes a broad-based, big-picture approach to funding research and building innovative collaborations to move the field forward. One example is our partnership with the Society of Nuclear Medicine and Molecular Imaging to develop and publish appropriate use criteria for PET brain amyloid imaging to assist Alzheimer's diagnosis."

"By 2050, the cost of caring people with Alzheimer's and other dementias is estimated to be more than $1 trillion annually in the United States alone. It is essential that we continue to gather scientific evidence at all levels, from the individual case study up to large-scale population-based research. The U.S. National Alzheimer's Plan was passed in 2012 and now must be fully implemented, and the commitment by the federal government to spend an additional $100 million on Alzheimer's and dementia research this year must be funded," Carrillo added.

No Evidence of Benefit in Population Screening for Dementia

Despite efforts to improve timely detection of dementia, it is estimated as many as 50 percent of people with dementia do not receive a formal diagnosis or receive it after the dementia has progressed significantly. Some advocates and policy makers propose population screening for dementia as a way of increasing early detection, though this remains controversial. The relative costs and benefits are still unclear.

As reported at AAIC 2013, Carol Brayne of Cambridge Institute of Public Health and colleagues conducted a systematic review of population screening studies. The researchers analyzed studies that looked at population screening either on its own or as a component of dementia intervention and compared outcomes with a routine pattern of care in the general population, among patients in general medical practice and among patients in community care. They identified eligible studies published by May 2012 through a broad search of the scientific literature.

The researchers found no evidence of the effect of screening on patient outcomes including cognitive, mental and emotional health, social function and planning. Based on the six studies that examined economic outcomes, the authors conclude that "substantial resources are required to screen for dementia"; costs depend on the age of the screened population, the properties of the screening instrument and the extent to which general practitioners are involved in follow-up assessments. The researchers were unable to identify any studies that looked at the potential harms caused by screening results, such as risk of depression, anxiety, stigma or loss of independence.

"We found no evidence that population screening would lead to better clinical or psychosocial outcomes, no evidence furthering our understanding of the risks it entails and no indication of its added value compared to current practice," said Brayne. "Policymakers should be very cautious about adopting population screening for dementia without any evidence of benefits or risks."

Alzheimer's Association Position on Dementia Screening in the Community

The Alzheimer's Association supports efforts that increase early detection and diagnosis of Alzheimer's disease by trained professionals in a medical setting — for example, the Association supports cognitive assessment as part of the Medicare Annual Wellness Visit, which is conducted in a controlled setting and administered by a trained clinician. At this time, the Alzheimer's Association does not support community-based memory screening.

The Association is working on many fronts to educate all stakeholders — individuals, families, physicians and policymakers — about the importance of early detection and early diagnosis and has developed a list of 10 Warning Signs of Alzheimer's Disease to assist with that effort. If individuals have experienced any of the following warning signs, it's important to seek a comprehensive diagnostic evaluation from a physician who is experienced in diagnosing and treating Alzheimer's.

Alzheimer's Association 10 Warning Signs of Alzheimer's Disease

For more information, visit: alz.org/10signs.

Misdiagnosis of Alzheimer's Disease Leads to Substantial Excess Costs

The misdiagnosis of Alzheimer's disease in Medicare patients who actually have vascular dementia or Parkinson's disease leads to substantial excess costs of care, according to a study conducted by Analysis Group Inc. and researchers from Eli Lilly and Company, and reported at AAIC 2013. They also found that those excess costs decline and eventually dissipate following a correct diagnosis.

The study authors analyzed administrative claims benefits for a random sample of Medicare beneficiaries and found that 17 percent of patients diagnosed with vascular dementia and 8 percent of patients diagnosed with Parkinson's disease had a prior incorrect diagnosis of Alzheimer's disease.

The researchers then retrospectively matched each previously misdiagnosed patient with a similar patient with no history of misdiagnosis, comparing the records of 2,088 matched pairs with vascular dementia and 2,058 pairs with Parkinson's. They found that during the time up to and including their confirmed correct diagnosis, the patients misdiagnosed with Alzheimer's disease incurred excess medical costs of up to $14,000 per year.

After the correct diagnosis, however, the excess costs dropped quickly. By the fourth year, on average, costs for previously misdiagnosed patients with both vascular dementia and Parkinson's disease were no higher than for patients who had never been misdiagnosed.

"Recent developments in technology have greatly improved our ability to properly diagnose patients with cognitive impairment," said Analysis Group's Noam Kirson. "Our results suggest that there are economic benefits to properly diagnosing — as early as possible — the cause of the cognitive impairment among patients with vascular dementia and Parkinson's disease. The U.S. healthcare system appears to be investing considerable resources due to misdiagnosis of Alzheimer's disease among these patients. Early diagnosis of other forms of dementia may help patients and providers avoid unnecessary costs and free up resources that could be used elsewhere."

(Note: Eli Lilly owns Avid Radiopharmaceuticals, which has a PET amyloid imaging compound that is FDA approved for visualization of amyloid plaque buildup in the brain and which can assist in ruling out Alzheimer's disease in those people with cognitive impairment.)

Experimental Imaging Agent Shows Promise in PET Detection of Tau in Alzheimer's

There are now substantial efforts underway to detect Alzheimer's earlier in the disease process — even before outward symptoms are noticeable or measurable — and also to identify changes happening in the brain that lead up to or effectively track the course of the disease. Tau pathology — tangles of misfolded tau protein in the brain — is a key biological marker of Alzheimer's disease, and one of the two well-recognized brains lesions characteristic of Alzheimer's disease; the other is amyloid plaques.

PET imaging agents for amyloid have been available to researchers for more than a decade, and one was approved by the FDA for clinical use in 2012. Similar compounds for imaging tau are just beginning to emerge, as shown in these next two reports from AAIC 2013.

A study by Hitoshi Shimada, M.D., Ph.D., of Japan's National Institute of Radiological Sciences and colleagues investigated the characteristics of [11C]PBB3, an experimental agent designed to bind to tau and make it visible on PET imaging in living people. Study participants, including people with Alzheimer's and age-matched healthy controls (more than 10 cases in both groups), were injected with an intravenous dose of [11C]PBB3 and given a PET scan. The study participants were also injected with [11C]PIB, an agent that binds to beta amyloid plaques, and scanned again.

PET imaging revealed high accumulation of [11C]PBB3 in different areas of the brain than [11C]PIB, as is appropriate in Alzheimer's. Distribution of the tau-binding agent in people with Alzheimer's extended to large areas of the brain; the distribution and degree of concentration correlated well with the participants' severity of disease.

"The results of this study support doing further research on [11C]PBB3 for detecting tau tangles in living persons," said Shimada. "Detecting the [11C]PBB3 binding agent throughout the brain may also show its ability to indicate the person's 'stage' of dementia, because tau abnormalities are closely correlated to dementia severity. These are promising early results, and much more work is needed."

Case Study Supports Experimental PET Tau Imaging Agent in Alzheimer's disease

A radioactive tracer compound known as [F-18]-T808, an experimental agent for tau binding in PET imaging, was recently tested in 12 people, including eight with cognitive impairment. The death of one of the participants in the study (unrelated to the procedure) allowed for a post-mortem analysis of brain tissue compared to the results of a previous PET scan of his brain.

The male study participant, aged approximately 85 years, had a clinical diagnosis of likely Alzheimer's disease five years prior to the study. According to Hartmuth Kolb, Ph.D., senior vice president of research, Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company, and colleagues, the [F-18]-T808 PET scan taken during the study suggested considerable tau pathology in most of the brain many of which are known to have tau buildup in Alzheimer's disease. The scientists found that a post-mortem analysis of the man's brain tissue was in agreement with the PET tau imaging results obtained with [F-18]-T808. In addition, the observed tau pathology appears to be consistent with the dementia experienced by the study participant.

"The observed pattern of [F-18]-T808 uptake in the subject's PET scan is very much consistent with what we found in the autopsy examination of tau deposition," Kolb said. "Though it is only one case study, these results support continued development of [F-18]-T808 and related PET tracers for identification of abnormal tau in the brains of people living with Alzheimer's disease."

About AAIC

The Alzheimer's Association International Conference (AAIC) is the world's largest conference of its kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders.  As a part of the Alzheimer's Association's research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

About the Alzheimer's Association

The Alzheimer's Association is the world's 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. Our vision is a world without Alzheimer's. For more information, visit www.alz.org or call 800.272.3900

SOURCE Alzheimer's Association