First demonstration that reduced metabolic activity in the hippocampus may be used to help predict future Alzheimer's disease

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."

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