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Imaging Breakthroughs Reveal Early AD Changes : New techniques detect preclinical changes in the brain's biochemistry, water diffusion, and structures.


 

The participants were from the ongoing Dartmouth Memory and Aging Study. The groups were balanced for age, education, and sex. They also were assessed using the California Verbal Learning Test.

DTI reveals disruptions of the white matter tracts that are not visible on MRI. Within white matter, water moves parallel to tracts. Conventional MRI can distinguish white from gray matter but can provide very little detail about the white matter; MRI cannot observe or quantify specific fiber tract directions.

DTI relies on the principle that water diffusion is affected by the properties of the medium in which it occurs. Diffusion within biologic tissues reflects tissue structure and architecture at the microscopic level.

In particular, the researchers looked at the ability of water to diffuse in different regions of the brain. The greater the diffusion, also known as trace diffusivity, the less white matter structure there is to limit movement—an indication of white matter degeneration.

An area of increased trace diffusivity—relative to the control group—was found in the right posterior cingulate of both the MCI group and the group with lesser cognitive complaints. The participants with MCI also showed increased trace diffusivity in medial temporal regions relative to the control group.

Relative to controls, patients with MCI were more likely to have increased trace diffusivity in the left and right anterior hippocampus and amygdala. Cerebral water diffusion in the group with lesser cognitive complaints was less than in those with MCI and greater than normal controls.

The researchers correlated trace diffusivity with performance They found that decreasing verbal scores on the California Verbal Learning Test correlated with increasing trace diffusivity in the left and right anterior hippocampus and amygdala.

The findings suggest that DTI could be sensitive to preclinical changes in regions of the brain associated with AD.

Previous studies using diffusion-tensor imaging (DTI) have shown increased diffusivity of water in the hippocampus of older adults with MCI, compared with healthy controls. This finding suggests early degenerative changes in the medial temporal region.

AD vs. Lewy Body Dementia on PET

PET imaging shows that patients with Lewy body dementia (LBD) have slightly more β-amyloid in the occipital and sensorimotor cortex than do patients with AD, a finding that may help physicians distinguish the two conditions with similar symptoms, according to a poster presented by Victor L. Villemagne, M.D., of Austin Hospital in Melbourne, Australia.

The researchers took advantage of a relatively new PET tracer—the Pittsburgh Compound B (PIB)—to image β-amyloid in the brain. PIB is a derivative of thiamine that is labeled with radioactive carbon and attaches to β-amyloid deposits in the brain that show up on PET imaging.

The researchers imaged eight patients with AD, seven patients with LBD, and seven age-matched healthy controls using PIB PET and

PIB PET images of the patients with AD showed marked binding in the frontal, parietal, and lateral temporal cortices, as well as the caudate nuclei, suggesting that there were significant β-amyloid deposits there. There was relative sparing of the occipital and sensorimotor cortex and very low uptake in the cerebellar cortex. Patients with LBD appeared similar to those with AD but slightly higher uptake was noted in the occipital and sensorimotor cortex.

The normal controls showed little or no PIB retention in any cortical and subcortical gray matter areas. Areas of PIB binding were inversely correlated with FDG uptake areas—a brain activity measure.

The use of PIB binding patterns can distinguish LBD from AD, said Dr. Villemagne, also of the department of pathology at the University of Melbourne.

LBD is the second most common dementia cause after AD, and it is difficult to distinguish the two disorders. Postmortem studies of LBD have shown that the majority of patients have cortical β-amyloid deposits similar to those in AD patients.

In addition, the researchers have also scanned individuals with Parkinson's disease and frontotemporal dementia using PIB-PET imaging. They found no cortical PIB retention, only white matter retention. α-Synuclein protein is the hallmark of certain neurodegenerative diseases. Tau protein forms the neurofibrillary tangles that are associated with AD.

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