Atrophy of the corpus callosum (CC) is involved in early Alzheimer’s disease (AD) and can be detected in subjects with very mild dementia in the early stage of AD, according to a study published in the May issue of Academic Radiology.

These changes in the CC indicate an anterior-to-posterior atrophic process as dementia worsens, according to study authors Zhiguo Lin, PhD, of the First Affiliated Hospital of Harbin Medical University in Harbin, China, and colleagues.

“The [CC], as the largest interconnecting white matter tract in the brain, may inevitably be affected by AD. Because the CC is responsible for most of the communication between the two cerebral hemispheres, it is important to understand how AD affects the CC,” wrote the authors.

The researchers used data sets from the Open Access Series of Imaging Studies to investigate callosal change. Study subjects, 196 in total, were characterized using the Clinical Dementia Rating (CDR), which assigns a rating of 0, 0.5, 1, 2 or 3 to represent varying stages of dementia, from none to severe. Included in the study were 98 healthy controls (CDR 0) and 98 patients with a clinical diagnosis of AD in the very mild or mild dementia stages (CDR 0.5 and 1, respectively). High-resolution structural MRI was performed on the patients and total and regional areas of the CC were measured.

Results showed that atrophy of the CC had occurred in patients with a CDR of 0.5. The area of the genu and rostral body of the CC was significantly different in healthy controls compared with those with very mild dementia. Likewise, significant differences existed in the rostral body and midbody of the CC between subjects with very mild dementia and those with mild dementia (CDR 1).

The changes between areas of the rostrum and genu to the midbody of the CC indicate that callosal atrophy occurs from the anterior to the posterior, with increasing degree of dementia as measured by the CDR.

“This finding also complements the myelin-breakdown hypothesis,” wrote the authors. “According to this hypothesis, small-diameter late-myelinating fibers are more susceptible to myelin breakdown and are more easily affected by neurodegeneration.” The authors noted that density of myelinate fibers decreases as the diameter of the fibers increases moving from the rostrum and genu to the midbody of the CC. This likely explains why callosal atrophy occurs anterior-to-posterior in the early stages of AD.

Lin et al noted that while multiple studies have documented callosal atrophy in patients with AD, the exact regions affected have been debated. Various studies have found that AD affects the anterior part of the CC only, while others found it affects the splenium or both the anterior and splenium. The authors contended that the Wallerian degeneration hypothesis, which involves the degeneration of nerve fibers along the axon away from the cell body, may not be as applicable as the myelin-breakdown hypothesis in explaining anterior atrophy of the CC.