Abstract
Background: Agitation and aggression are common in dementia and pre-dementia. The dementia risk syndrome mild behavioral impairment (MBI) includes these symptoms in the impulse dyscontrol domain. However, the neural circuitry associated with impulse dyscontrol in neurodegenerative disease is not well understood. The aim of this work is to investigate if regional micro- and macro-structural brain properties are associated with impulse dyscontrol symptoms in older adults with normal cognition, mild cognitive impairment, and Alzheimer’s disease. Methods: Clinical, neuropsychiatric, and T1-weighted and diffusion-tensor MRI (DTI) data from 80 individuals with and 123 individuals without impulse dyscontrol, were obtained from the Alzheimer’s Disease Neuroimaging Initiative. Linear mixed effect (LME) models were used to assess if impulse dyscontrol was related to regional DTI and volumetric parameters. Results: Impulse dyscontrol was present in 17% of participants with NC, 43% with MCI, and 66% with AD. Impulse dyscontrol was associated with: 1) lower fractional anisotropy, and greater mean, axial, and radial diffusivity in the fornix; 2) lesser fractional anisotropy, and greater radial diffusivity in the superior fronto-occipital fasciculus; 3) greater axial diffusivity in the cingulum; 4) grey matter atrophy, specifically, lower cortical thickness and greater surface area in the parahippocampal gyrus. Conclusion: Our findings provide evidence that well-established atrophy patterns of AD are prominent in the presence of impulse dyscontrol, even when disease status is controlled for, and possibly in advance of dementia. Our findings support the growing evidence base for impulse dyscontrol symptoms as an early manifestation of Alzheimer’s disease.
Prevention Studies in Alzheimer’s Disease: Progress Towards the Development of New Therapeutics
