Can You Find It? Novel Oddity Detection Task for the Early Detection of Alzheimer’s Disease

Objective: We aimed to develop a measure to specifically assess the functioning of the perirhinal cortex (PRC), a brain structure affected very early in Alzheimer’s disease (AD) pathology. In this novel task, participants were shown arrays of six complex figures and had to identify the “odd-one.” Method: The pilot study included 50 normal controls (NCs) and 50 patients in very early stages of AD. Participants completed the task and received MRI scanning. Best differentiating items were determined and applied in a validation study including 25 NCs, 27 early-stage AD patients, and 26 patients with major depression. Logistic regression models investigated if task performance predicted group membership. Task performance was then related to whole-brain gray matter integrity. As proof of concept, cortical thickness values of four regions of interest (ROIs; e.g., medial PRC and entorhinal cortex [ERC]) were compared between the groups. The associations of task performance and cortical thickness of the ROIs were investigated using linear models. Results: Task performance showed good discriminative ability between early-stage AD patients and NCs. Whole-brain analyses revealed four significant clusters (p <.001) with peak voxels in parahippocampal regions including PRC and ERC. ROI analyses showed distinctly reduced cortical thickness in the AD group compared to both other groups in the medial PRC and ERC (p ≤.001). Task performance modeled by ROI cortical thickness did not achieve significant results. Conclusion: Although further validation is needed, especially with age-matched participant groups, these findings indicate that the task detects early cognitive impairment related to AD.