Callosal circularity as an early marker for Alzheimer's disease

Background: Although brain atrophy is considered to be a downstream marker of Alzheimer's disease (AD), subtle changes may allow to identify healthy subjects at risk of developing AD. As the ability to select at-risk persons is considered to be important to assess the efficacy of drugs and as MRI is a widely available imaging technique we have recently developed a reliable segmentation algorithm for the corpus callosum (CC). Callosal atrophy within AD has been hypothesized to reflect both myelin breakdown and Wallerian degeneration. Methods: We applied our fully automated segmentation and feature extraction algorithm to two datasets: the OASIS database consisting of 316 healthy controls (HC) and 100 patients affected by either mild cognitive impairment (MCI) or Alzheimer's disease dementia (ADD) and a second database that was collected at the Memory Clinic of Hospital Network Antwerp and consists of 181 subjects, including healthy controls, subjects with subjective cognitive decline (SCD), MCI, and ADD. All subjects underwent (among others) neuropsychological testing including the Mini-Mental State Examination (MMSE). The extracted features were the callosal area (CCA), the circularity (CIR), the corpus callosum index (CCI) and the thickness profile. Results: CIR and CCI differed significantly between most groups. Furthermore, CIR allowed us to discriminate between SCD and HC with an accuracy of 77%. The more detailed callosal thickness profile provided little added value towards the discrimination of the different AD stages. The largest effect of normal ageing on callosal thickness was found in the frontal callosal midbody. Conclusions: To the best of our knowledge, this is the first study investigating changes in corpus callosum morphometry in normal ageing and AD by exploring both summarizing features (CCA, CIR and CCI) and the complete CC thickness profile in two independent cohorts using a completely automated algorithm. We showed that callosal circularity allows to discriminate between an important subgroup of the early AD spectrum (SCD) and age and sex matched healthy controls.