The pattern of cortical thickness underlying disruptive behaviors in Alzheimer's disease

Background: Disruptive behaviors, including agitation, disinhibition, irritability, and aberrant motor behaviors, are commonly observed in patients with Alzheimer's disease (AD). However, the neuroanatomical basis of these disruptive behaviors is not fully understood.

Objective: To confirm the differences in cortical thickness and surface area between AD patients and healthy controls and to further investigate the features of cortical thickness and surface area associated with disruptive behaviors in patients with AD.

Methods: One hundred seventy-four participants (125 AD patients and 49 healthy controls) were recruited from memory clinics at the Peking University Institute of Sixth Hospital. Disruptive behaviors, including agitation/aggression, disinhibition, irritability/lability, and aberrant motor activity subdomain scores, were evaluated using the Neuropsychiatry Inventory. Both whole-brain vertex-based and region-of-interest-based cortical thickness and surface area analyses were automatically conducted with the CIVET pipeline based on structural magnetic resonance images. Both group-based statistical comparisons and brain-behavior association analyses were performed using general linear models, with age, sex, and education level as covariables.

Results: Compared with healthy controls, the AD patients exhibited widespread reduced cortical thickness, with the most significant thinning located in the medial and lateral temporal and parietal cortex, and smaller surface areas in the left fusiform and left inferior temporal gyrus. High total scores of disruptive behaviors were significantly associated with cortical thinning in several regions that are involved in sensorimotor processing, language, and expression functions. The total score of disruptive behaviors did not show significant associations with surface areas.

Conclusion: We highlight that disruptive behaviors in patients with AD are selectively associated with cortical thickness abnormalities in sensory, motor, and language regions, which provides insights into neuroanatomical substrates underlying disruptive behaviors. These findings could lead to sensory, motor, and communication interventions for alleviating disruptive behaviors in patients with AD.