White matter integrity disrupted in people with Alzheimer’s disease gene mutation – sciencedaily


The structural integrity of the brain’s white matter as measured with an advanced MRI technique is lower in cognitively normal people who carry a genetic mutation associated with Alzheimer’s disease than in non-carriers, study finds carried out in Radiology. The researchers said the findings show the promise of widely available imaging techniques to help understand the early structural changes in the brain before symptoms of dementia become apparent.

People with the autosomal dominant Alzheimer’s disease (ADAD) mutation have a higher risk of Alzheimer’s disease, a type of dementia that affects about one in nine people in the United States. The mutation is linked to a buildup of an abnormal protein called beta-amyloid in the brain that affects both gray matter and white matter that carries signals.

“It is believed that deposition of amyloid in gray matter could disrupt its function, and therefore white matter will not function properly or may even atrophy,” said lead author Jeffrey W. Prescott said. , MD, Ph.D., neuroradiologist at MetroHealth Medical Center in Cleveland.

An earlier study by Dr Prescott and colleagues in patients with sporadic Alzheimer’s disease, which accounts for 99% of cases, found that the structural connectivity of white matter, as measured with an MRI technique called Diffusion tensor imaging (DTI) deteriorated dramatically as patients developed more amyloid load.

“Current work extends these results by showing that similar results are detectable in asymptomatic risk patients,” said Jeffrey R. Petrella, MD, professor of radiology at Duke University and lead author of both studies.

In the new study, Dr Prescott and colleagues used data from the Dominantly Inherited Alzheimer Network (DIAN) to compare carriers of the ADAD mutation with non-carriers to see if there were any changes in structural connectivity. that could be linked to the mutation.

Study participants included 30 carriers of the mutations, mean age 34, and 38 non-carriers, mean age 37. The participants all had normal cognition when they underwent structural brain MRI and DTI.

Analysis showed that carriers of the mutations had lower structural connectivity in the fronto-parietal control network, which connects areas primarily in the parietal and frontal lobes, two regions known to be involved in Alzheimer’s disease. Among the carriers of the mutations, there was a correlation between the expected years until symptom onset and the structural connectivity of white matter in the fronto-parietal control network, even while controlling the amyloid plaque load.

“This suggests that DTI measures of network integrity may serve as a surrogate for brain resilience to disease attacks,” said Dr Petrella.

“We used a network metric called overall efficiency, in which a decrease in efficiency can be seen as a breakdown in the organization of the network,” added Dr Prescott. “The results show that for carriers of the mutations, the overall efficacy would decrease significantly as the estimated age of symptom onset approaches.”

Study results support a potential role for the imaging identification of structural changes in the brain in people at genetic risk of developing Alzheimer’s disease at an early stage in understanding the influence of genes on the process. pathological that leads to dementia.

“This shows the potential of MRI as an assessment tool in patients deemed at risk for Alzheimer’s disease before they develop symptoms,” said Dr Prescott. “The use of these advanced MRI techniques could help further refine the identification of patients at risk and measures of risk.”

The results also indicate a role for imaging in the study of therapeutic drugs to treat Alzheimer’s disease. While the majority of trials so far have been performed with patients already with Alzheimer’s disease or cognitive impairment, the earlier identification and treatment of at-risk patients represents a more promising avenue for preventing or reducing. less delay the onset of dementia.

“A potential clinical use of this study tool would be to add quantitative information to risk factors such as family history and use it to help identify patients early, when they may benefit from treatment,” Dr Prescott said. “But until we have an effective treatment, we will have to wait for it to be implemented.”

The researchers hope to follow up using advanced imaging and updated data from the DIAN network to assess the progression of Alzheimer’s disease in study participants.

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