Brain imaging techniques sharpen focus on Alzheimers
Recent advances in brain imaging may allow very early diagnosis of Alzheimers and other dementias, and improved assessment of treatment effectiveness
Imaging techniques such as PET and MRI are near to becoming useful in diagnosing Alzheimers disease earlier and distinguishing it from other types of dementia, according to research reported today at the 9th International Conference on Alzheimers Disease and Related Disorders (ICAD), presented by the Alzheimers Association.
For example, one study at the conference reports the latest data on a new PET technology that allows researchers to see – for the first time – accumulations of the abnormal protein tau in the brains of people with a rare form of dementia.
"Having the ability to observe the damage and progression of Alzheimers in the living brain will have a profound impact on how we diagnose the disease, as well as how we gauge the effectiveness of current medical treatments and those in development," said William Thies, Ph.D., vice president of Medical & Scientific Affairs for the Alzheimers Association.
Researchers View the Early Stages of Alzheimers In the Brain
Advances in positron emission tomography (PET) allow researchers to evaluate brain changes of people whose mild cognitive impairment (MCI) may represent the early stages of Alzheimers. William E. Klunk, M.D., Ph.D., and colleagues at the University of Pittsburgh have recently developed a compound known as Pittsburgh Compound-B (PIB) – visible on PET scans – that sticks to abnormal clumps of protein in the brain called amyloid plaques. Plaques and other abnormal protein aggregates called tangles are the hallmarks of Alzheimers disease. The main component of the plaques, a toxic protein fragment called beta-amyloid, is a primary suspect in the death of brain cells in Alzheimers.
Klunk and colleagues presented PET scan data from a preliminary study of five people with MCI. They found that the subjects fall into two distinct groups. One group has evidence of amyloid deposition that is indistinguishable from normal controls, and the other group has evidence of amyloid deposition that is indistinguishable from Alzheimers disease patients.
Some people with MCI progress to Alzheimers while others do not. It may be that levels of amyloid in the brain are related to who develops the disease. The researchers will attempt to replicate these results in a much larger study.
"Amyloid imaging with PET may become useful for predicting which people with MCI will progress to Alzheimers in the near future. The technology might also help to determine the effectiveness of anti-amyloid therapies in people with MCI and Alzheimers," said Klunk.
First Visualization of "Tangles" in Frontotemporal Dementia
Another PET development allows researchers to see–for the first time–accumulations of the abnormal protein tau in the brains of people with a rare form of dementia. Gary Small, M.D., of the University of California, Los Angeles, and his colleagues have developed a PET compound, [F-18]FDDNP, that "sticks" both to amyloid plaques and the tangles of abnormal tau protein in the brains of Alzheimers patients. In their report at ICAD, the researchers used this new compound to map the tangles also found in frontotemporal dementia (FTD), a rare disorder with symptoms similar to Alzheimers.
"We believe this is the first time tau accumulation has been visualized in living patients," said Small. "The new technique may help us better differentiate between Alzheimers and other forms of dementia – leading to more effective treatments."
The researchers compared PET scans of people with FTD and Alzheimers. They found very different distributions of protein accumulations. The different patterns may serve as a useful tool to differentiate Alzheimer and FTD patients. The researchers hope the technique also can be used to monitor the effectiveness of drugs to clear abnormal proteins such as tau from the brain.
MRI Shows Ability to Distinguish Possible Early Alzheimers and Effects of Treatment
A combination of anatomic and functional magnetic resonance imaging (MRI), which can detect brain abnormalities in people with Alzheimers disease, may also be able to identify brain changes in people who complain of cognitive deficits but do not meet the criteria for a diagnosis of MCI or Alzheimers.
Andrew J. Saykin, Psy.D., of Dartmouth Medical School, Lebanon, New Hampshire, leads a team following the progress of 90 older adults as they age. At the outset of the study, 30 of the participants reported no significant declines in memory or other mental functions, while another 30 had cognitive deficits that warranted a diagnosis of MCI. The remaining 30 participants – termed the cognitive complaint group – had perceived deficits in memory and other mental functions that did not reach the threshold for MCI diagnosis and could not be explained by depression or other health problems. The researchers are employing repeat MRI scans to track changes in gray matter and brain activity during memory task performance and comparing the three groups over time. However, even in the baseline study, a surprising parallel was noted between the cognitive complaint and MCI groups.
"The pattern of reduction of gray matter and brain activity in the older adults who complained of cognitive deficits was almost identical to that seen in patients with MCI, suggesting that many of these people may be in the earliest stages of Alzheimers," said Saykin. "Early detection will be essential as new preventative and treatment strategies become available."
The 9th International Conference on Alzheimers Disease and Related Disorders (ICAD), presented by the Alzheimers Association, is the largest gathering of Alzheimer researchers in history. More than 4,500 scientists from around the world will present and discuss the findings of 2,000 studies showcasing the newest treatment advances in Alzheimers disease and steps toward prevention. ICAD will be held July 17-22, 2004, at the Pennsylvania Convention Center in Philadelphia, Pennsylvania.