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JULY 28, 2008
  Detecting Alzheimer’s Disease Earlier: Penn Researchers Identify Promising Indicators
  Research Refines Targets for Drug Development
   

PHILADELPHIA – Researchers from the School of Medicine have identified two new techniques to detect the progression of Alzheimer’s disease earlier. By catching Alzheimer’s disease before symptoms are apparent, physicians can prescribe treatments to slow down the disease progression. In one study, researchers identified abnormal structural changes in the brains of seemingly normal elderly that indicated mild cognitive impairment, a precursor to Alzheimer’s disease. In a second study, researchers detected changes in cells that may help predict the transition from mild cognitive impairment to Alzheimer’s disease. The studies were presented this week at the 2008 Alzheimer’s Association International Conference on Alzheimer’s Disease.

Christos Davatzikos, PhD, Professor of Radiology at the University of Pennsylvania School of Medicine, Susan Resnick, PhD, of the National Institute on Aging and colleagues found brain deterioration in elderly adults who were classified as cognitively normal. They used a highly accurate measurement tool, based on MRI images from the brains of people with Alzheimer’s disease, to look at the MRI images of normal elderly and identify any remarkable structural changes. By comparing these images, researchers were able to identify subtle structural changes in the brain tissue of healthy elderly with no noticeable symptoms of Alzheimer’s disease.

“With the development of this technique, we hope clinicians will be able to detect structural brain changes that are typical of Alzheimer’s disease earlier, before individuals present cognitive decline, by measuring levels of brain deterioration,” said Dr. Davatzikos. “We plan to integrate MRI with other biomarkers and especially with imaging of amyloid plaques, the protein deposits in the brain associated with Alzheimer’s disease.”

Results of the study demonstrated:

  • Significant brain deterioration was evident a number of individuals who had no apparent symptoms when compared to cognitively healthy elderly.
  • An increase of changes or abnormalities in brain structure was accompanied by a decrease in cognitive performance.
  • There was an increase in Alzheimer’s-like brain deterioration as people aged.

In addition, researchers uncovered a connection between two risk factors for dementia. Alzheimer’s-like structural changes were accompanied by diseases of small blood vessels in the brain.

Predicting Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

In a second study, Dr. Leslie Shaw, Professor of Pathology and Lab Medicine and Director of the Penn ADNI Biomarker Core Laboratory, and colleagues found they could predict when patients with mild cognitive impairment may convert to Alzheimer’s disease by measuring significant cellular signatures.

Researchers determined benchmark concentration levels of certain biological indicators in three populations: elderly who were cognitively normal, mildly cognitively impaired and had Alzheimer’s disease. Examining cerebral spinal fluid (CSF) samples collected from more than 50 study sites, they determined baseline levels of three proteins associated with Alzheimer’s disease (total tau, P-Tau181P, and ß-Amyloid1-42). What they found were significant differences in the level of these biomarker concentrations between groups.

“Analyzing changes in these CSF biomarker levels in people with mild cognitive impairment can detect the conversion to Alzheimer’s disease, especially when used in conjunction with neuroimaging and psychological tests,” said Dr. Shaw. “By defining significant differences in biomarkers, we are able to accelerate our drug development efforts to look for compounds that modify these discrepancies and may treat Alzheimer’s disease.”

Dr. Davatzikos’ study used MRI images from participants in two long term studies – the Baltimore Longitudinal Study of Aging (BLSA) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) – and was funded by the National Institute on Aging and the Institute for the Study of Aging. Data collection and collaboration for Dr. Shaw’s project was funded by the Alzheimer’s Disease Neuroimaging Initiative through a grant from the National Institutes of Health.

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Penn's School of Medicine is currently ranked #4 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.

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