Diffusion Tensor MRI Reveals Brain Connection Failure in Early Alzheimer’s Disease

White matter connections are vital for conducting communication across the billions of nerve cells in the brain. DTI may provide help in assessing brain injury in early AD and tracking the effect of new therapies.

According to the researchers, changes in brain connections visible on DTI magnetic resonance imaging (MRI) scans could represent an imaging biomarker of AD, according to the findings that were presented December 1, 2014, at the annual meeting of the Radiological Society of North America (RSNA), held in Chicago (IL, USA).

AD is the most typical form of dementia. As many as five million Americans are affected, a number expected to grow to 14 million by 2050, according to the US Centers for Disease Control and Prevention (Atlanta, GA, USA). Preventive treatments may be most effective before AD is diagnosed, such as when an individual is suffering from mild cognitive impairment (MCI), a decline in cognitive skills that is noticeable but not severe enough to affect independent function. Earlier efforts at early detection have focused on beta amyloid, a protein found in abnormally high amounts in the brains of individuals with AD.

For the new study, researchers looked at the brain’s structural connectome, a map of white matter tracts that carry signals between different areas of the brain. “The structural connectome provides us with a way to characterize and measure these connections and how they change through disease or age,” said study coauthor Jeffrey W. Prescott, MD, PhD, radiology resident at Duke University Medical Center (Durham, NC, USA).

Dr. Prescott and colleagues analyzed study findings from 102 patients enrolled in a national study called the Alzheimer’s Disease Neuroimaging Initiative (ADNI) 2. The patients had undergone diffusion tensor imaging (DTI), an MRI method that assesses the integrity of white matter tracts in the brain by measuring how easy it is for water to move along them. “It is known that water prefers moving along the defined physical connections between regions in the brain, which makes DTI a great tool for evaluating the structural connectome,” Dr. Prescott said.

The researchers compared alterations in the structural connectome with findings from florbetapir positron emission tomography (PET) imaging, a technique that measures the amount of beta amyloid plaque in the brain. Increased florbetapir uptake corresponds with greater amounts of the protein. The findings revealed a strong association between florbetapir uptake and decreases in strength of the structural connectome in each of the five areas of the brain studied.

“This study ties together two of the major changes in the brains of AD patients, structural tissue changes and pathological amyloid plaque deposition, and suggests a promising role for DTI as a possible diagnostic adjunct,” Dr. Prescott said.

Based on these findings, DTI may offer a role in evaluating brain damage in early AD and monitoring the effect of new therapies. “Traditionally, Alzheimer’s disease is believed to exert its effects on thinking via damage to the brain’s gray matter, where most of the nerve cells are concentrated,” said Jeffrey R. Petrella, MD, professor of radiology at Duke and senior author on the study. “This study suggests that amyloid deposition in the gray matter affects the associated white matter connections, which are essential for conducting messages across the billions of nerve cells in the brain, allowing for all aspects of mental function.”

“We suspect that as amyloid plaque load in the gray matter increases, the brain's white matter starts to break down or malfunction and lose its ability to move water and neurochemicals efficiently,” added Dr. Prescott.

The researchers plan to continue examining this cohort of patients over time to gain a better determination of how the disease evolves in individual patients. They also intend to integrate functional imaging into their research to learn about how the relationship between function and structure is affected with increasing amyloid burden.

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Duke University Medical Center