Study Identifies Associations Between Hyperactive Neuropsychiatric Symptoms and Brain Morphology for Patients With Mild Cognitive Impairment and Alzheimer Disease

A recent database study found that hyperactive neuropsychiatric symptoms (NPS) —agitation, disinhibition, and irritability—are associated with distinct brain regions in patients with Alzheimer disease (AD), mild cognitive impairment (MCI), and older adults with normal cognition.

Despite being one of the most challenging symptoms to manage in AD, hyperactive NPS and their underlying brain correlates have been poorly studied.

Enter El Haffaf and colleagues, who utilized data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to analyze neuropsychiatric assessments and 3T MRI scans from 216 patients with AD, 564 individuals with MCI, and 660 cognitively normal older adults.

The researchers used a general linear model (GLM) that encompassed all three groups (AD, MCI, CN). Next, they conducted pair-wise GLMs (AD vs MCI, MCI vs CN, AD vs CN) to distinguish the subtle differences in brain structure associations between groups. El Haffaf and colleagues used multiple regression analyses to identify cortical changes that were then correlated with the severity of hyperactive NPS.

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The results from the overall GLM indicated associations with distinct brain morphologies, particularly differences in volume, thickness, and surface area. Indeed, researchers found associations between (1) agitation and the right parietal supramarginal surface area in the MCI-CN contrast, (2) disinhibition and the cortical thickness of the right frontal pars opercularis and temporal inferior in the AD-MCI contrast, and (3) irritability and the right frontal pars opercularis, frontal superior, and temporal superior volumes in the MCI-CN contrast.

“Our study shows that each hyperactive NPS is associated with distinct brain regions in AD, MCI, and CN (groups with different levels of cognitive performance),” the researchers concluded. “This suggests that each NPS is associated with a unique signature of brain morphology, including variations in volume, thickness, or area.”

Reference
El Haffaf LM, Ronat L, Cannizzaro A, Hanganu A; Alzheimer’s Disease Neuroimaging Initiative. Associations between hyperactive neuropsychiatric symptoms and brain morphology in mild cognitive impairment and Alzheimer's disease. J Alzheimers Dis. 2024;97(2):841-853. doi:10.3233/JAD-220857