Modifications within the white matter within the mind in frontotemporal dementia

Areas of brain damage called white matter hyperintensities are often associated with vascular health problems. They have also been linked to Alzheimer’s disease. Now a new study has shown that white matter hyperintensities also occur in frontotemporal dementia. The study was published in the online edition of Neurology®, the American Academy of Neurology’s medical journal, February 17, 2021. Frontotemporal dementia, which often affects people under the age of 65, mainly results in changes in personality, behavior and problems with language rather than memory.

We expected similar levels of white matter hyperintensities in frontotemporal dementia and Alzheimer’s disease, but we actually found higher levels in people with frontotemporal dementia. We also expected that people with more severe disease would have more white matter hyperintensities regardless of their condition, but this was only true for people with frontotemporal dementia.

Study author Ramón Landin-Romero, Ph.D., from the University of Sydney, Australia.

The study included 64 people with frontotemporal dementia, 65 people with Alzheimer’s disease, and 66 people without dementia who had brain scans and other tests. The participants were followed for an average of two years. Autopsy information was available for 13 people with frontotemporal dementia and five people with Alzheimer’s disease.

The researchers found that the total volume of white matter hyperintensities in the brain was greater in people with frontotemporal dementia than in people with Alzheimer’s disease or the healthy control group. The average volume of white matter hyperintensities in people with frontotemporal dementia was 0.76 milliliters (ml) compared with 0.40 ml in people with Alzheimer’s disease and 0.12 ml in people without dementia.

The amount of white matter hyperintensities was associated with the severity of a person’s frontotemporal dementia, including the severity of their symptoms and everyday difficulties, but not as expected with vascular risk factors such as high blood pressure and high cholesterol.

In general, white matter hyperintensities have been linked to these vascular risk factors, so these results suggest that white matter hyperintensities are partially independent of vascular factors and are related to the progressive loss of brain integrity, particularly the loss of brain cells due to frontotemporal, are associated with dementia. White matter hyperintensities should be viewed as a core feature of frontotemporal dementia and Alzheimer’s disease, which can contribute to cognitive problems, rather than just markers of vascular disease.


The researchers also found that higher levels of white matter hyperintensities in certain areas of the brain were linked to poorer cognitive performance. For example, in both frontotemporal dementia and Alzheimer’s disease, increased white matter hyperintensity in the corpus callosum, a bundle of white matter fibers connecting the left and right hemispheres of the brain, has been associated with attention problems.

One limitation of the study was that autopsy information was only available for a small number of cases, so the underlying molecular cause for the white matter hyperintensities could not be determined for the participants.

The study was supported by the Australian National Health and Medical Research Council and the Appenzeller Neuroscience Fellowship in Alzheimer’s.

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