Thanks to long-term studies using brain imaging and biomarker analysis, scientists know that physiological signs of Alzheimer's disease begin to appear long before individuals notice changes in their memory. New guidelines for diagnosing Alzheimer's, put forth today by the National Institute on Aging and Alzheimer's Association, recognize the earliest stages of the neurodegenerative disorder and encourage the use of early monitoring technologies in drug development. In fact, given the difficulty in developing treatments for the disease, it may be that the most effective drugs need to be delivered very early in disease progression.

"The new guidelines reflect today's understanding of how key changes in the brain lead to Alzheimer's disease pathology and how they relate to the clinical signs of mild cognitive impairment and Alzheimer's disease dementia," said Creighton Phelps, program director of the Alzheimer's Disease Centers Program at the National Institutes of Health, in a press release from the Alzheimer's Association. "We are also beginning to be able to detect these changes at a preclinical stage, long before symptoms appear in many people. With further research on biomarkers, as set forth in the new guidelines, we may ultimately be able to predict who is at risk for development of mild cognitive impairment and Alzheimer's dementia, and who would benefit most as interventions are developed."

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According to the authors, in order to facilitate the possibility of future presymptomatic treatment of Alzheimer's, it was important to define the disease from the earliest changes in the brain, not only the observable, symptomatic stages of the disease. The authors propose that Alzheimer's begins with a long asymptomatic period during which detrimental changes are progressing in the brain, and individuals with biomarker evidence of these changes are at increased risk for developing cognitive and behavioral impairment and progression to Alzheimer's dementia.

For now, the change will mainly be felt in clinical trials rather than in standard clinical practice, as scientists use these technology to monitor the effectiveness of experimental drugs.

According to the New York Times.

For now, the guidelines specify that Alzheimer's biomarkers — including abnormal levels of the proteins amyloid and tau, and shrinkage of certain brain areas — should not yet be put into widespread use, but used only with patients enrolled in clinical trials.

That is because scientists cannot yet standardize the results of the tests, or know "what measure is truly abnormal and what measure is not," said Marilyn Albert, director of the Johns Hopkins Alzheimer's Disease Research Center, and a leader of one working group that developed the new guidelines.

As many as a third of people with amyloid plaques in their brains, for example, have not developed Alzheimer's symptoms by the time they die. The guidelines also urge caution because there is currently no drug known to halt or significantly delay the onset of symptoms, so people told they are likely to get Alzheimer's have no effective medication to take.

"We don't have enough information about what to tell people," said Dr. Steven DeKosky, dean of the University of Virginia medical school, who participated in one of the working groups. "Until you can tell a clinician, 'If you do this test you have X amount of reliability and to do that will make a difference in the life of your patient' — until then, it remains in the lab."

Tone-deaf people--those who can't hold a tune--appear to be missing a specific neural circuit, according to research published today in the Journal of Neuroscience.

Researchers used a variation of MRI called diffusion tensor imaging to compare neural circuits--specifically those between the right temporal and frontal lobes--in the brains of people who are tone-deaf and those who are not.

According to a press release from the Society for Neuroscience, which published the research,

This region, a neural "highway" called the arcuate fasciculus, is known to be involved in linking music and language perception with vocal production.The arcuate fasciculus was smaller in volume and had a lower fiber count in the tone-deaf individuals. More notably, the superior branch of the arcuate fasciculus in the right hemisphere could not be detected in the tone-deaf individuals. The researchers speculated that this could mean the branch is missing entirely, or is so abnormally deformed that it appears invisible to even the most advanced neuroimaging methods.

Healthy young people who carry a genetic variant that raises the risk for Alzheimer's disease show differences in the brain decades before memory problems typically arise, according to research published today in the Proceedings of the National Academy of Sciences. Brain-imaging studies found that carriers had a hyperactive hippocampus, part of the brain central to learning and memory, even when mentally at rest. Scientists involved in the study say that the findings support the idea that the memory part of the brain is overworked in high-risk people, which over time could contribute to the disease.

Researchers used functional magnetic brain imaging to assess brain activity in 36 adults ages 20 to 35, half of whom carried at least one copy of the at-risk variation, and all of whom performed normally on tasks designed to test their cognitive skills. Not everyone who carries the variant, called APOE4, will develop Alzheimer's. But those who have one copy have a quadrupled risk of the disease, while those with two copies have about ten times the average risk.

According to a press release from Imperial College London,

Differences in the region of the brain involved in memory, known as the hippocampus, have previously been shown in middle-aged and elderly healthy carriers of APOE4. However, the new Oxford University and Imperial study is the first to show hyperactivity in the hippocampus of healthy young carriers. It is also the first to show that APOE4 carriers' brains behave differently even at "rest."

Dr. Christian Beckmann, another author of today's study from the Division of Neurosciences and Mental Health at Imperial College London, added: "Our brains are always active--our minds wander even when we're not carrying out specific tasks. We were surprised to see that even when the volunteers carrying APOE4 weren't being asked to do anything, you could see the memory part of the brain working harder than it was in the other volunteers. Not all APOE4 carriers go on to develop Alzheimer's, but it would make sense if in some people, the memory part of the brain effectively becomes exhausted from overwork and this contributes to the disease. This theory is supported by studies that have found the opposite pattern in people who have developed Alzheimer's, with these people showing less activity than normal in the memory part of the brain."