Background: Pathological studies in Alzheimer dis- ease indicate the specific loss of layer III and V large py- ramidal neurons in association cortex. These neurons give rise to long corticocortical connections within and be- tween the cerebral hemispheres. Objective:To evaluate the corpus callosum as an in vivo marker for cortical neuronal loss. Method: Using a new imaging technique, we mea- sured region-specific corpus callosum atrophy in patients with Alzheimer disease and correlated the changes with neuropsychological functioning. Total cross-sectional area of the corpus callosum and areas of 5 callosal subregions were measured on mid- sagittal magnetic resonance imaging scans of 14 patients with Alzheimer disease (mean age, 64.4 years; Mini-Mental State Examination score, 11.4) and 22 healthy age- and sex-matched control subjects (mean age, 66.6 years; Mini-Mental State Examination score, 29.8). All subjects had minimal white matter changes. Results: The total callosal area was significantly re- duced in the patients with Alzheimer disease, with the greatest changes in the rostrum and splenium and rela- tive sparing of the callosal body. Regional callosal atro- phy correlated significantly with cognitive impairment in the patients with Alzheimer disease, but not with age or the white matter hyperintensities score. Conclusions: Callosal atrophy in patients with Alzhei- mer disease with only minimal white matter changes may indicate loss of callosal efferent neurons in correspond- ing regions of the cortex. Because these neurons are a sub- set of corticocortical projecting neurons, region-specific callosal atrophymayserve as a marker of progressive neo- cortical disconnection in Alzheimer disease.
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