Imaging for Alzheimer’s: White matter degeneration a biomarker on DTI

Physicians and researchers are still unsure how or where Alzheimer disease begins in the brain, but a new study has found that white matter degeneration—detectable using diffusion tensor imaging (DTI)—could be a reliable biomarker for atypical variations of the brain disease. The results of the study were published online May 27 in the journal Radiology.

While traditional Alzheimer disease is characterized by progressive memory deterioration, other forms of the disease such as early-onset Alzheimer disease can affect a diverse range of brain regions, according to lead author Francesca Caso, MD, of San Raffaele University in Milan, Italy, and colleagues. “One possible mechanism that could explain the involvement of different brain regions in [Alzheimer disease] variants is the spread of disease via distinct brain networks,” wrote the authors. “[T]au aggregates may start to accumulate in some vulnerable networks and then propagate transneuronally through white matter connections, gradually reaching unaffected regions from affected ones.”

Caso and her research team used DTI to assess white matter degeneration in 53 patients with atypical Alzheimer disease, including early-onset Alzheimer's, logopenic variant of primary progressive aphasia, and posterior cortical atrophy. They analyzed the results to define overlapping and syndrome specific patterns of brain damage and to identify similarities and differences across the different Alzheimer variants.

Their results showed that every patient studied showed similar patterns of white matter degeneration and regional gray matter damage, as well as cortical atrophy. “When we looked at the commonly altered cortical regions, we found that the three groups shared a pattern of atrophy, including the left temporoparietal regions and precuneus,” wrote Caso and colleagues. “More importantly, we demonstrated that the microstructural [white matter] damage is more severe and more widely distributed than expected on the basis of cortical atrophy in all clinical phenotypes studied.”

The researchers emphasized the importance of their findings regarding the usefulness of DTI to accurately image the possible white matter biomarker. “Our findings indicate that DT MR imaging may be able to demonstrate subtle abnormalities along [white matter] pathways that link atrophic regions with still unaffected gray matter regions,” the authors wrote. “More importantly, we found that DT MR imaging has the potential to allow assessment of the extensive disorganization of brain networks in focal [Alzheimer disease], even before overt cognitive deficits become apparent.”

Caso and her team believe their findings highlight the need for more studies into the mechanics and processes of the mysterious disease. “Longitudinal studies of patients with [atypical Alzheimer disease] in the early and/or prodromic stages of disease, by using more sophisticated statistical models such as generalized linear mixed models are now warranted to confirm our model and elucidate the direction of the disease spreading in [Alzheimer disease].”