New computer program uses brain scans to assess risk of Alzheimer's

New York University School of Medicine researchers have developed a brain scan-based computer program that quickly and
accurately measures metabolic activity in a key region of the brain affected in the early stages of Alzheimer's disease.
Applying the program, they demonstrated that reductions in brain metabolism in healthy individuals were associated with the
later development of the memory robbing disease, according to a new study.


"This is the first demonstration that reduced metabolic activity in the hippocampus may be used to help predict future
Alzheimer's disease," says Lisa Mosconi, Ph.D., a research scientist in the Department of Psychiatry, who developed the
computer program and led the new study. "Although our findings need to be replicated in other studies," she says, "our
technique offers the possibility that we will be able to screen for Alzheimer's in individuals who aren't cognitively
impaired."


Dr. Mosconi and colleagues have recently published the technical details of the program, called "HipMask," in the June 2005
issue of the journal Neurology. She will present the new findings on June 20 at the Alzheimer's Association International
Conference on Prevention of Dementia held in Washington.


The computer program is an image analysis technique that allows researchers to standardize and computer automate the sampling
of PET brain scans. The NYU researchers hope the technique will enable doctors to measure the metabolic rate of the
hippocampus and detect below-normal metabolic activity.


The technique grew out of years of research by Mony de Leon, Ed.D., Professor of Psychiatry and Director of the Center for
Brain Health. His group was the first to demonstrate with CT and later with MRI scans that the hippocampus, a sea-horse
shaped area of the brain associated with memory and learning, diminishes in size as Alzheimer's disease progresses from mild
cognitive impairment to full-blown dementia.


Yet until now there has been no reliable way to accurately and quickly measure the hippocampal area of the brain on a PET
scan. The hippocampus is small and its size and shape are affected greatly in individuals with Alzheimer's, making it
difficult to sample this region. HipMask is a sampling technique that uses MRI to anatomically probe the PET scan.


MRI relies on electromagnetic energy to excite water molecules in the brain to create an anatomical map of the brain. The MRI
was used in the study to determine the total volume of the hippocampus and then to define that portion (namely the HipMask)
that was shared by all persons regardless of their disease status. PET employs radioactively labeled glucose to show the
brain at work and the HipMask was applied to these scans to derive estimates of the hippocampal glucose metabolism.


The researchers followed 53 healthy, normal subjects between the ages of 54 and 80 for at least 9 years and in some cases for
as long as 24 years. All subjects received two FDG-PET scans -- one at baseline and a follow-up after 3 years. Thirty
individuals had a second follow-up scan after another seven years. Altogether there were 136 PET scans.


The researchers applied the HipMask to all 136 scans. The results showed that hippocampal glucose metabolism, as determined
by the HipMask, was significantly reduced 15% to 40% on the first scan, compared to controls, of those 25 individuals who
would later experience cognitive decline related to either mild cognitive impairment or to Alzheimer's. The researchers found
that the baseline hippocampal glucose metabolism was the only brain or clinical measure that predicted the future cognitive
decline.


"Right now, we can show with great accuracy who will develop Alzheimer's nine years in advance of symptoms, and our
projections suggest we might be able to take that out as far as 15 years," says Dr. de Leon, whose longitudinal study is
funded by the National Institutes of Health (NIH).


"Our basic results will need to be replicated in other studies and expanded to include PET data from diverse patient groups,"
adds Dr. De Leon. "But we're confident this is a strong beginning, demonstrating accurate detection of early Alzheimer's
disease. Now we have a better tool to examine disease progression, and we anticipate this might open some doors to prevention
treatment strategies."


Contact: Pamela Mcdonnell

pamela.mcdonnellnyumc

212-404-3555

New York University Medical Center and School of Medicine

med.nyu