VANCOUVER—In patients with Alzheimer’s disease, white matter deteriorated significantly in the frontal lobe over two years, according to a study presented at the 2012 Alzheimer’s Association International Conference. Principal white matter fibers deteriorated in areas including the bilateral forceps minor, anterior cingulate gyrus, inferior fronto-occipital fasciculus, thalamic radiation, and uncinate fasciculus.
Post hoc analysis including age and sex as covariates revealed a trend of white-matter deterioration over two years in the left frontal cortex of patients with Alzheimer’s disease, said Rodrigo Perea, a doctoral candidate in the bioengineering program at the University of Kansas School of Medicine in Kansas City. The trend was observed in the inferior fronto-occipital fasciculus, uncinate fasciculus, forceps minor, and cingulate gyrus.
The Brain Aging Study
To examine how white matter neurodegeneration occurs during the course of Alzheimer’s disease, Mr. Perea and colleagues studied 18 participants in the University of Kansas Brain Aging Study. This study was led by Jeffrey Burns, MD, Associate Director of the University of Kansas’s Alzheimer’s Disease Center. The researchers performed diffusion tensor imaging and administered cognitive tests at baseline and after two years. The team characterized diffusivity by mean diffusivity and fractional anisotropy.
Nine participants, including seven females, had been diagnosed with early stages of Alzheimer’s disease. Their mean age was approximately 70, and their mean Clinical Dementia Rating (CDR) was 0.5. Nine other participants, including four females, were healthy controls with a mean age of nearly 72.
The investigators performed nonparametric permutation voxelwise statistics using the generalized linear model to test the difference in diffusivity between patients with and without Alzheimer’s disease. The researchers applied threshold-free cluster enhancement to correct for multiple comparisons and reported significant results.
Larger Samples Could Confirm the Pattern of Degeneration
Mr. Perea and colleagues found no significant differences in age, sex, education, and APOE e4 presence between the two groups of patients, and they excluded these characteristics as covariates in their initial analysis. Patients with early stages of Alzheimer’s disease had significantly lower baseline Mini-Mental State Examination scores and CDR sum of boxes.
“While hippocampal and parietal atrophy are the hallmarks of Alzheimer’s disease, my results show a higher rate of prefrontal white matter degeneration that could later lead to behavioral changes,” Mr. Perea told Neurology Reviews. “These results will help future treatments to focus not only on the hallmark regions of the brain, but also on other regions that could have higher atrophy once the disease is diagnosed,” he concluded.
—Erik Greb