Corpus callosum anatomical changes in Alzheimer patients and the effect of acetylcholinesterase inhibitors on corpus callosum morphometry

Abstract

The Corpus Callosum (CC) is an important structure that includes the majority of fibers connecting the two brain hemispheres. Several neurodegenerative diseases may alter CC size and morphology leading to its atrophy and malfunction which may play a role in the pathological manifestations found in these diseases. The purpose of the current study is to determine any possible changes in CC size in patients suffering from Alzheimer's disease. The Study also investigated the effect of acetylcholinesterase inhibitors (AChEIs) on the size of CC and its association with improvement in the Alzheimer disease severity scores. Midsagittal size of CC were recorded prospectively from 439 routine T1-weighted MRI brain images in normal individuals. The internal skull surface was measured to calculate CC/ internal skull surface ratio. Two groups of patients were studied: 300 (150 male / 150 female) were healthy subjects and 130 (55 males / 75 females) had Alzheimer disease. Out of the 130 Alzheimer disease pateints, 70 patients were treated with Donepezil or Rivastigmine or both. The size of the CC was measured based on T1-weighted MRI images after the treatment to investigate any possible improvement in CC size. The mean surface area of CC in controls was 6.53±1.105 cm2. There was no significant difference between males and females (P < 0.627), and CC/ internal skull surface ratio was 4.41±0.77%. Patients with mild or severe Alzheimer disease showed a significant reduction in CC size compared to healthy controls. Treating mild Alzheimer patients with either Donepezil or Rivastigmine exerts a comparable therapeutic effect in improving the CC size. There was more improvement in the size of CC in patients with severe Alzheimer disease by using combined therapy of Donepezil and Rivastigmine than using single a medication. we measured the mean size of the various portions of the corpus callosum in normal individuals and Alzheimer patients before and after taking Donepezil and Rivastigmine. Alzheimer patients have pronounced reduction in CC which is corrected after taking Donepezil and Rivastigmine leading to remarkable improvement in Alzheimer disease severity scores.

Fig 1. Delineation and partitioning of the midsagittal corpus callosum in T1-weighted MR images.

The corpus callosum was traced in the three most medial brain slices. A, CC area is in red and whole skull surface is in yellow and B, length of the CC; C, CC thickness at genu, body, and splenium.

Fig 2. Adjusted corpus callosum CC mean values for the three diagnostic groups; normal controls, mild Alzheimer patients, and severe Alzheimer patients.

Corpus callosum (CC) mean values were significantly smaller in Alzheimer patients compared to normal controls. Moreover, the CC area and size decreases as the severity of Alzheimer increases, thus severe Alzheimer patients have significant reduction in the CC size compared to mild Alzheimer patients. Each column represents the mean CC area ± standard error of the mean (SE). *P<0.05, **<0.01 (t-test).

Fig 3. Descriptive data for the treated Alzheimer patients.

Fig 4. Percentage of improvement in Alzheimer severity scores after acetylcholinesterase inhibitors (AChEIs) medications were given to the patients.

No significant difference reported between Donepezil treatment group and Rivastigmine treatment group in the degree of improvement in severity scores. On the other hand, severe cases of Alzheimer showed a more significant increase after using a Donepezil and Rivastigmine combined therapy than using a single medication. Each column represents the percentage of severity score improvement ± standard error of the mean (SE). *P<0.05 (t-test).

Fig 5. Percentage of improvement in MMSE score with each medication.

The best improvement in MMSE score was seen when using a combined therapy with donepezil and rivastigmine in contrast with a single medication.

Fig 6. A scatter plot show the mean CC improvement versus mean MMSE score improvement for each medication.

The scotter plot showed that MMSE score improvement was assocaiated with increase in CC size, moreover, using a using combined therapy with donepezil and rivastigmine gives a better improvement in both MMSE score and CC size compared with a single medication.