As people get older, changes occur in all parts of the body, including the brain. In the brain:
The impact of these changes differs among people as they age. Healthy older people may notice only a modest reduction in their ability to learn new things, retrieve information from memory, and plan and make decisions. Other people, however, experience much greater declines in their memory and cognitive abilities as they grow older because they are developing a neurodegenerative disease and these changes are occurring to a much greater extent. Understanding the difference between changes that occur with healthy aging and a neurodegenerative process is an important key to unlocking the secrets of AD.
It is now clear that by the time the symptoms of amnestic MCI or AD become evident, the disease process is well underway—neurons have died, plaques and tangles have become abundant in different brain regions, and damage from inflammation and free radicals has greatly increased. Decades earlier, biological processes may have begun that predisposed the individual to develop AD or another neurodegenerative disease. As the previous sections of this report show, it is also increasingly clear that these biological processes are directed by a complex interaction of many factors, including genetic, lifestyle, and environmental influences.
If the disease process actually starts many years before it becomes evident, while a person still appears to be healthy, then it is imperative for researchers to learn as much as possible about its early stages so that they can identify those who may be at high risk and develop interventions to disrupt or prevent the disease. Advances in several key tools are helping scientists understand these early changes in the brain:
A New York University School of Medicine group recently conducted a longitudinal study of cognitively healthy people and those with MCI. This study, the first to combine data from memory testing, MRI scans, and CSF biomarkers, found that combining these different types of measures consistently improved diagnostic accuracy (de Léon et al., 2006). Compared to cognitively healthy people, those with MCI showed decreased memory performance, decreased hippocampal size, and increased CSF levels of tau and isoprostane, two substances known to be often abnormal in AD. Moreover, levels of isoprostane increased significantly over a 2-year time period. This elevation was associated with decreases in CSF beta-amyloid levels and decreased hippocampal volume, suggesting a progression of degeneration consistent with AD.
For the moment, these technologies are used primarily in experimental contexts but, some day, they could be used more widely in clinical settings as a diagnostic tool. The findings from the New York University School of Medicine study, for example, support the idea that an accurate, reliable, and possibly specific clinical diagnosis of AD in the MCI stage is a reasonable expectation. As these tools improve and become more widely available, they also could be used to predict and follow the course of AD and other neurodegenerative diseases as well as to explain similarities and differences among them. Another important application of these advances is in measuring response to treatments, which would be invaluable in clinical trials of new drugs. Some day, as the influence of diet, exercise, intellectual stimulation, and other lifestyle factors on AD risk is clarified, these tools may even be useful in tracking changes in risk that result from behavioral and lifestyle changes. (For more on how this might be done, see the Alzheimer’s Disease Neuroimaging Initiative described in "Major AD Research Initiatives".)
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