Alzheimer's plaques in PET brain scans identify future cognitive decline

12 july 2012--Among patients with mild or no cognitive impairment, brain scans using a new radioactive dye can detect early evidence of Alzheimer's disease that may predict future decline, according to a multi-center study led by researchers at Duke University Medical Center.

The finding is published online July 11, 2012, in the journal Neurology, the medical journal of the American Academy of Neurology. It expands on smaller studies demonstrating that early detection of tell-tale plaques could be a predictive tool to help guide care and treatment decisions for patients with Alzheimer's disease.

"Even at a short follow-up of 18 months we can see how the presence of amyloid plaques affects cognitive function," said P. Murali Doraiswamy, M.D., professor of psychiatry at Duke who co-led the study with R. Edward Coleman, M.D., professor of radiology at Duke . "Most people who come to the doctor with mild impairment really want to know the short-term prognosis and potential long-term effect."

Doraiswamy said such knowledge also has some pitfalls. There is no cure for Alzheimer's disease, which afflicts 5.4 million people in the United States and is the sixth-leading cause of death among U.S. adults. But he said numerous drugs are being investigated, and identifying earlier disease would improve research into their potential benefits and speed new discoveries, while also enhancing care and treatment of current patients.

In the Neurology study, 151 people who had enrolled in a multi-center test of a new radioactive dye called florbetapir (Amyvid) were recruited to participate in a 36-month analysis. Of those participants, 69 had normal cognitive function at the start of the study, 51 had been diagnosed with mild impairment, and 31 had Alzheimer's dementia.

All completed cognitive tests and underwent a brain scan using Positron Emission Tomography, or PET imaging. The technology uses radioactive tracers designed to highlight specific tissue to create a three-dimensional picture of an organ or a biological function.

The dye used in the study, florbetapir, was recently approved by the U.S. Food and Drug Administration for PET imaging of the brain to estimate beta-amyloid plaque density in patients who are being evaluated for cognitive impairment. It binds to the amyloid plaques that characterize Alzheimer's disease, providing a window into the brain to see if the plaques have formed, and how extensively.

Patients in the study were reassessed with additional cognitive exams at 18 months and 36 months. At the 18-month point, patients with mild cognitive impairment who had PET evidence of plaque at the trial's start worsened to a great degree on cognitive tests than patients who had no evidence of plaque at the trial's start. Twenty-nine percent of the plaque-positive patients in this group developed Alzheimer's dementia, compared to 10 percent who started with no plaque.

Cognitively normal patients with a plaque-positive PET scan at the start of the study also showed more mental decline at 18 months compared to those who were negative for plaque.

The study additionally found that people with negative scans reversed from minimally impaired to normal more often than people with positive PET scan, suggesting test anxiety or concentration problems could have affected their initial performance.

"For the most part we have been blind about who would progress and who wouldn't, so this approach is a step toward having a biomarker that predicts risk of decline in people who are experiencing cognitive impairment," Doraiswamy said.

He said the study's results provide initial data that needs to be verified by additional research. Final, 36-month data from the study has been completed and will be presented at the Alzheimer's Association International Conference this week in Vancouver, Canada. Doraiswamy also cautioned that florbetapir is currently not approved to predict the development of dementia or other neurologic conditions and stressed that it should not be used as a screening tool in otherwise normal or minimally impaired people. Likewise, a positive scan is not necessarily diagnostic for Alzheimer's by itself.

Provided by Duke University Medical Center

A decade of research proves PET effectively detects dementia

In a new review of imaging studies spanning more than ten years, scientists find that a method of positron emission tomography (PET) safely and accurately detects dementia, including the most common and devastating form among the elderly, Alzheimer's disease. This research is featured in the January issue of the Journal of Nuclear Medicine.

07 jan 2012--Researchers reviewed numerous PET studies to evaluate a molecular imaging technique that combines PET, which provides functional images of biological processes, with an injected biomarker called 18F-FDG to pinpoint key areas of metabolic decline in the brain indicating dementia. Having physiological evidence of neurodegenerative disease by imaging patients with PET could give clinicians the information they need to make more accurate diagnoses earlier than ever before.

"The new data support the role of 18F-FDG PET as an effective addition to other diagnostic methods used to assess patients with symptoms of dementia," says Nicolaas Bohnen, MD, PhD, lead author of the study and professor of radiology and neurology at the University of Michigan, Ann Arbor, Mich. "The review also identified new literature showing the benefit of this imaging technique for not only helping to diagnose dementia but also for improving physician confidence when diagnosing a patient with dementia. This process can be difficult for physicians, especially when evaluating younger patients or those who have subtle signs of disease."

Dementia is not a specific illness but a pattern of symptoms characterized by a loss of cognitive ability. These disorders can be caused by injury or progressive disease affecting areas of the brain that control attention, memory, language and mobility. While Alzheimer's is most commonly associated with progressive memory impairment, dementia with Lewy bodies, another form of the disease, can be associated with symptoms of Parkinson's and prominent hallucinations, while another disorder, called frontotemporal dementia, can be seen in patients showing uncharacteristic personality changes and difficulties in relating and communicating. Physicians can use FDG-PET with high accuracy to not only help diagnose dementia but also differentiate between the individual disorders. The role molecular imaging plays in the diagnosis of dementia has expanded enough that the official criteria physicians use to diagnose patients now includes evidence from molecular imaging studies.

"For the first time, imaging biomarkers of Alzheimer's disease are included in the newly revised clinical diagnostic criteria for the disease," says Bohnen. "This is a major shift in disease definition, as previously an Alzheimer's diagnosis was based mainly on a process of evaluating patients to exclude possible trauma, hemorrhage, tumor or metabolic disorder. Now it is becoming a process of inclusion based on biomarker evidence from molecular imaging."

The PET biomarker 18F-FDG comprises a radionuclide combined with fluorodeoxyglucose (FDG), which mimics glucose in the body. Cells metabolize FDG as fuel, and the variation in this uptake by cells throughout the body can then be imaged to detect a range of abnormalities. In the case of dementia, marked reductions in the metabolism of different lobes of the cerebral cortex can confirm a patient's disorder. Physicians can tell Alzheimer's disease apart from other dementias, depending on the specific cortices affected.

This review presents the most up-to-date and salient evidence of FDG-PET's usefulness for the evaluation of patients with suspected dementia. The objective of the study was to replace prior retrospective reviews that were performed as the technique was just emerging and that suggested methodological improvements. The new review includes studies with better methodology, including confirmation of diagnoses with autopsy, more expansive recruitment of subjects and use of multi-center studies. After reviewing 11 studies that occurred since the year 2000 and that met more stringent study review standards, researchers conclude that 18F-FDG is highly effective for detecting the presence and type of dementia.

"Using 18F-FDG PET in the evaluation of patients with dementia can improve diagnostic accuracy and lead to earlier treatment and better patient care," says Bohnen. "The earlier we make a diagnosis, the more we can alleviate uncertainty and suffering for patients and their families."

The biomarker 18F-FDG is among a variety of imaging agents being investigated for its efficacy in Alzheimer's imaging. As treatments for dementia become available for clinical use, PET will no doubt play an important role in not only the diagnosis of these diseases, but also the assessment and monitoring of future therapies.

According to the World Health Organization, an estimated 18 million people worldwide are currently living with Alzheimer disease. That number is projected to almost double by 2025.

More information: "Effectiveness and safety of FDG-PET in the evaluation of dementia: a review of the recent literature" Journal of Nuclear Medicine. http://jnm.snmjournals.org/

Provided by Society of Nuclear Medicine

PET Detection of Amyloid Levels Equal to Immunohistochemistry

Amyloid levels detected by florbetapir-PET standard uptake value ratio characterizes AD, MCI

13 july 2011-- Detection of amyloid levels by positron emission tomography (PET), measuring fluorine 18-labeled flutemetamol (florbetapir) uptake by the brain cortex, is in concordance with immunohistochemical estimation; and the florbetapir-PET standard uptake value ratios (SUVRs) help characterize amyloid levels in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), according to two studies published online July 11 in the Archives of Neurology.

David A. Wolk, M.D., from the University of Pennsylvania in Philadelphia, and colleagues investigated the concordance of in vivo quantitative estimates of florbetapir brain uptake in PET scans with immunohistochemical estimates of amyloid levels in seven patients who had a previous cortical biopsy. They found a complete agreement between florbetapir-PET scans and histology. Taking time from biopsy as a covariate, they identified a significant relationship between florbetapir uptake and percentage of area of amyloid measured by a monoclonal antibody raised against amyloid.

Adam S. Fleisher, M.D., from the Banner Alzheimer's Institute in Phoenix, and colleagues characterized florbetapir-PET measurements of fibrillar β-amyloid (Aβ) burden and compared mean cortical florbetapir SUVRs in 68 patients with AD, 60 with MCI, and 82 older healthy controls (OHCs). Participants with probable AD and MCI, and OHCs differed significantly in mean cortical florbetapir SUVRs, in the percentage meeting SUVR criteria of levels of amyloid associated with AD (80.9, 40.0, and 20.7 percent, respectively), and in percentage meeting SUVR criteria for the presence of any identifiable Aβ (85.3, 46.6, and 28.1 percent, respectively).

"The findings of our analysis confirm the ability of florbetapir-PET SUVRs to characterize amyloid levels in clinically probable AD, MCI, and OHC groups using continuous and binary measures of fibrillar Aβ burden," the authors write.

Several authors from Wolk's study disclosed financial relationships with GE Healthcare, which also funded the study. Several authors from Fleisher's study disclosed financial ties to the pharmaceutical industry, including Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly, which funded the study.

Abstract - Wolk
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