Mind

How Does an Alzheimer's Brain Compare to a Normal One?

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In order to identify abnormalities like nerve cell damage and overall brain shrinkage related to Alzheimer's disease, it is necessary to know what a normal elderly brain should look like. Some parts of the brain vary widely from one individual to the next, while other parts look nearly identical. This map, created by comparing the location of thousands of specific points in many healthy brains, shows which is which. Red indicates a point of high variability, blue reflects places where brains tend to look alike, and green indicates areas in between.

On the previous slide is a composite "mesh" map of an average healthy elderly brain. Even healthy brains lose some cells over time, but the image on the right reveals how dramatic cell loss in the brain of an Alzheimer's victim can be. The blue areas are where no excess tissue is lost relative to an average brain. Green shows areas of some neurodegeneration, and red indicates significant loss. While ADNI researchers use maps such as these to study the pattern and range of degeneration among groups of patients over time, this model could also be used to monitor the progress of the disease in a single patient.

Composite images document brain tissue loss (blue) and expansion of the fluid-filled ventricles (red) that swell to fill the space over one year. Degeneration accelerates as individuals develop mild cognitive impairment (MCI), an intermediate stage between health and dementia. Images 1 through 3 show composite normal, MCI, and AD brains. Image 4 reveals the difference in tissue loss between MCI and normal; image 5 depicts the difference between AD and MCI, and 6 contrasts an AD brain with healthy normal tissue. Opposite: A schematic of the brain shown on this page. The temporal lobes, associated with memory and cognition, are in green.

This image of an Alzheimer's patient's neural network--viewed from above, with the front of the brain on the right--was created using diffusion tensor imaging, a technique that tracks water molecules moving along the length of the axons that link neuron to neuron.

Drawing on ADNI data, which helped link Alzheimer's disease to a common gene called CLU, researchers used this imaging technique in other people to discover that the brain wiring of gene carriers is impaired decades before the disease typically strikes. As the ADNI initiative grows, so will its power to uncover and attack AD at its genetic roots.

Each subject's brain is comprehensively imaged once a year using magnetic resonance imaging (MRI), a technique that employs an electromagnetic field to detect the shape and density of tissue. After analysis, the images will be preserved alongside the subject's clinical data, including genetic information and scores on cognitive tests.

1. First, each image is preprocessed to remove noise introduced by the scanning equipment and to strip out irrelevant details such as the skull.

2. Next, the brain shape and structure are mapped, including the grooves--called sulci, shown in pink--in the folded cortex.

3. Software measures the neuron-rich gray matter in the brain's outer cortex, the underlying fibers of the white matter, and the clear fluid that fills the cavities.

4. A composite is created by averaging the shape and size of all the healthy elderly brains in the ADNI database.

5. Researchers can compare individual subjects' brains to the standard brain.

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