Progression of corpus callosum atrophy in Alzheimer disease.

BACKGROUND: Atrophy of the corpus callosum in the absence of primary white matter degeneration reflects loss of intracortical projecting neocortical pyramidal neurons in Alzheimer disease (AD). OBJECTIVES: To determine individual rates of atrophy progression of the corpus callosum in patients with AD and to correlate rates of atrophy progression with clinical disease severity and subcortical disease. METHODS: Magnetic resonance imaging-derived measurements of corpus callosum size were studied longitudinally in 21 patients clinically diagnosed as having AD (mean observation time, 17.0 +/- 8.5 months) and 10 age- and sex-matched healthy controls (mean observation time, 24.1 +/- 6.8 months). RESULTS: Corpus callosum size was significantly reduced in AD patients at baseline. Annual rates of atrophy of total corpus callosum, splenium, and rostrum were significantly larger in AD patients (-7.7%, -12.1%, and -7.3%, respectively) than in controls (-0.9%, -1.5%, and 0.6%, respectively). Rates of atrophy of the corpus callosum splenium were correlated with progression of dementia severity in AD patients (rho = 0.52, P<.02). The load of subcortical lesions at baseline (P<.05) predicted rate of anterior corpus callosum atrophy in healthy controls. Rates of atrophy of corpus callosum areas were independent of white matter hyperintensity load in patients with AD. CONCLUSIONS: Measurement of corpus callosum size allows in vivo mapping of neocortical neurodegeneration in AD over a wide range of clinical dementia severities and may be used as a surrogate marker for evaluation of drug efficacy.

Age transformation of combined hippocampus and amygdala volume improves diagnostic accuracy in Alzheimer's disease.

OBJECTIVE: The specificity of magnetic resonance imaging (MRI)-based hippocampal measurements in detecting Alzheimer's disease (AD) pathology is reduced by an age-related reduction of the hippocampus volume. We propose an adjustment for this age effect to increase the diagnostic accuracy of hippocampal volumes in AD. METHOD: Using an orthogonal rotational transformation of the coordinate system, values of MRI-determined volumes of hippocampus-amygdala formation (HAF) were transformed according to the age effect in 27 AD patients and 28 age- and sex-matched healthy control subjects. RESULTS: The age transformation increased the diagnostic accuracy of HAF volumes in the study sample and in an independent sample from the literature. The age-transformed HAF volume predicted AD in a subject with mild cognitive impairment (MCI) with later biopsy-confirmed AD. CONCLUSION: Age transformation may provide an easily applicable method to increase the clinical diagnostic accuracy of hippocampal measurements by considering the effect of aging on hippocampus volume.