Apathy in Alzheimer's disease: Eye movements characteristics and neurostructural basis

Background: We sought to evaluate the characteristics of eye movements in Alzheimer's disease (AD) patients with apathy (AD-A) and their ability to identify AD-A and explore the shared neurostructure of eye movements and apathy.

Methods: Total 32 normal controls, 36 AD-A and 72 AD with no apathy (AD-NA) patients were recruited. Parameters of smooth pursuit, fixation, prosaccade and antisaccade were compared among the three groups. Correlation analyses were conducted on apathy score, eye movement parameters and gray matter volume (GMV) in AD patients. Receiver operating characteristic curves were used to determine the power of eye movement parameters to identify AD-A patients.

Results: AD-A group exhibited a longer start-up duration of smooth pursuit, latency of gap and overlap prosaccades than AD-NA and normal control groups. In AD patients, apathy score was positively correlated with latency of overlap prosaccade. The GMVs of right pregenual anterior cingulate cortex (ACC) and left supracallosal ACC were negatively correlated with apathy score. Regions shared by apathy and latency of overlap prosaccade included right pregenual ACC and left supracallosal ACC. The area under curve discriminated AD-A from AD-NA patients by combining start-up duration, latency of gap and overlap prosaccade, and demographic information was 0.812.

Conclusions: AD-A patients exhibit delayed initiation in eye movements, and the more prominent apathy indicates prolonged latency of overlap prosaccade in AD patients. Apathy and latency of overlap prosaccade share a neurostructural basis in AD patients. Our results contribute to providing a new method for early identification and severity assessment for AD-A.