NEUROIMAGING MEASURES THE EFFECT OF A TREATMENT ON THE BRAIN

Research Published May 29 2015
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It is crucial in the search for new treatments for neurodegenerative diseases to identify biomarkers that enable measurement of their effect on the brain. In a clinical trial in patients with early stage Alzheimer disease, an image analysis program developed by the ARAMIS team in the Brain and Spine Institute enabled the researchers to measure the effect of a pharmacological agent on the volume of the hippocampus visualized by MRI. The study was published in the journal Alzheimer’s and Dementia.

The search for new treatments for neurodegenerative diseases requires their evaluation in clinical trials. It is, thus, crucial to be able to measure the effect of these treatments on the brain, not just their cognitive and/or clinical effects. Magnetic resonance imaging (MRI), in particular, enables analysis of atrophy in different brain structures, which reflects neuronal and synaptic loss in neurodegenerative diseases. The challenge was to develop methods for quantifying atrophy with great precision on MRI images.

The researchers have just shown that it is possible to measure the slowing of brain atrophy by a pharmacological agent, thanks to an image analysis program that they developed. The study was a clinical trial of dondpezil, a molecule that is used to treat the symptoms of Alzheimer disease. This national collaborative project involved Marie Chupin, Olivier Colliot and Didier Dormont in the ARAMIS team of the Brain and Spine Institute (ICM), Stéphane Lehéricy of the Centre for Neuroimagery Research of the ICM, Bruno Dubois and Marie Sarazin of the Memory and Alzheimer disease Institute and the pharmaceutical companies EISAI and Pfizer.

The study aimed at determining whether the treatment could slow atrophy of the hippocampus in patients with early-stage Alzheimer disease. The hippocampus is a structure in the temporal lobe of the brain that plays a major role in memory. It is also one of the first regions of the brain to be altered by Alzheimer disease. Marie Chupin in the ARAMIS team developed a program to automatically measure the volume of the hippocampus from magnetic resonance imaging (MRI) data.

For the study, 216 patients with early stage Alzheimer diseases were recruited. Half of them received donepezil, the other half a placebo. The automated volumetry enabled the researchers to show that the rate of loss of hippocampal volume was reduced by 45% in patients receiving donepezil compared to those receiving the placebo. This technique opens promising perspectives for the evaluation of new therapeutic approaches to neurodegenerative diseases.

ARAMIS, in the Brain and Spine Institute, is a joint team of the CNRS, Inria, Inserm and Pierre and Marie Curie University. It was part of the Laboratory of Cognitive Neuroscience and Brain Imagery (LENA, CNRS UPR 640) directed by Line Garnero, who initiated and coordinated these studies until her tragic death in 2009.