Researchers measure cerebral metabolite levels in people with mild memory problems

Using powerful and targeted but non-invasive magnets on specific brain sites of people with and without mild learning and memory problems, Johns Hopkins researchers indicate that they were able to detect differences in the concentrations of brain chemicals that transmit messages between neurons. The strength of these magnetic fields allows researchers to measure very small amounts and compare multiple levels of brain metabolites at the same time. These studies may ultimately help to reveal what triggers the decline in memory and perhaps even predict the risk of dementia.

Researchers believe that measuring these data over time will allow them to more accurately detect and describe changes in brain metabolism as a person goes from a healthy to mild cognitive impairment to dementia. .

The results were published in the January issue of Neurobiology of aging.

"We hope to one day use this technology to understand the early changes in brain chemistry badociated with cognitive and behavioral symptoms that may represent new treatment targets," says Richman Family Professor Gwenn S. Smith, Ph.D. of Alzheimer's and Related Diseases, Department of Psychiatry and Behavioral Sciences of the Johns Hopkins University School of Medicine and Director of the Division of Geriatric and Neuropsychiatric Psychiatry. "At the present time, we do not know the biological cerebral mechanism that causes memory disorders, and we think that by using this technique we will eventually be able to understand the chemical changes in the brain that trigger these damage, and maybe even one day intervene to prevent it. "

The researchers say they have detected a decrease in two specific chemical messengers, GABA and glutamate, in people with mild cognitive impairment, compared to those who are not.

Previous studies conducted by the researchers showed that other types of brain imaging, including PET scans, could detect neurotransmitters – the chemical messengers of the brain – serotonin and dopamine. These two chemicals are involved in mood, memory and cognitive decline. However, each chemical measured in this way requires its own PET-Scan.

The technology used in the new study, MRS, is very similar to magnetic resonance imaging (MRI), which uses strong magnetic fields and radio waves to create organ. While MRI primarily measures brain water, MRS has long been used to identify chemical degradation products, or metabolites, in an unknown substance, based on unique peaks or "signatures" of the brain. substances generated in response to certain vibrations. MRS uses a combination of a powerful magnet and radio waves to stimulate molecules in the brain to perform tiny and distinct tilt movements. A computer badysis then identifies the chemical metabolites based on the location of the spikes on a scale that ranks the chemicals according to the rate at which the signals appear during these tilting movements. The height and width of the tips on the scale determine the amount of chemical present in the targeted brain area.

The researchers explain however that, when using routine and clinical MRIs, the product tips bleed into each other and that chemicals with similar structures can not be distinguished from each other. The researchers began using a device with a more powerful magnet, called 7-Tesla. The intensity of the magnetic field of this machine is more than 100,000 times higher than that of the Earth's magnetic field.

"We are seeing extremely low concentrations of chemicals in the brain, with concentrations about 50,000 times lower than water, essentially proverbial needles in a haystack," says Georg Oeltzschner, Ph.D. , postdoctoral fellow at Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine. "Very weak signals and sensitive technology explain why this technique has not been widely used to measure the signals of the chemicals we are interested in. Thanks to the powerful magnet, we are able to improve signal and resolution decisively. "

"These different chemicals can be measured in one scan and complement those in the brain that we can measure with PET scanning," says Smith.

While waiting to see differences in the chemical composition of the brain in people with mild cognitive impairment compared to healthy people, the researchers recruited 13 people with mild cognitive impairment and 13 healthy controls. Seven of the 26 participants were women and the average age was 67 years old.

To confirm that participants had a mild cognitive impairment, they had to score at least one and a half standard deviation below the normal range of the California oral test or the abbreviated visuospatial memory test. Memory. Using a PET-scan to measure amyloid protein plaques early in the brain of people with the disease, they confirmed that each participant with mild cognitive impairment had evidence of these protein plaques.

The researchers wanted to measure the neurotransmitters and brain metabolites found in parts of the brain known to show changes in people with Alzheimer's disease: the anterior cingulate cortex and the posterior cingulate cortex. Both places are located in the part of the brain responsible for thought and mood in the central midline that divides the brain into right and left hemispheres, one at the front of the head and the other at the back. Each MRS scan of a specific region of the brain with the 7 Tesla magnet took about 5 to 10 minutes to obtain sufficient resolution and signal strength of the chemical components in each of the brain locations.

The researchers identified and compared the levels of the neurotransmitters GABA and glutamate, the metabolite N-acetylaspartylglutamate, glutathione antioxidant and markers of neuronal health, N-acetylaspartate and myo-inositol, which indicate inflammation of the brain.

According to Smith, the most striking result is a 16% decrease in the level of GABA in the brains of people with mild cognitive impairment compared to healthy people, using chemical creatine as a reference to standardize metabolic rates. One person to the other. For example, in the region at the front of the brain, the GABA / creatine ratio was 0.42 in healthy people, compared with 0.34 in people with mild cognitive impairment. They also found a decrease of about 6% in glutamate in the brains of people with mild cognitive impairment.

"This pilot study shows that we can use MRS to measure individual metabolites in the brain and detect changes in chemicals in the brain between healthy people and those at risk of contracting Alzheimer's disease" Smith said. "We can now prepare a larger study with more people to get more meaningful results."

Dr. Oeltzschner also announced his intention to apply new measurement techniques to measure GABA and other low-level metabolites on the most common MRI devices with 3.0 Tesla magnets. These new techniques may allow more places to perform this type of measurement, because 7 Tesla machines are expensive and still relatively rare.