Neural Correlates of the Impulse Dyscontrol Domain of Mild Behavioral Impairment

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.

Prevalence of mild behavioural impairment domains: a meta‐analysis

“…They are associated with neurodegenerative change and progressive cognitive decline, and have predictive utility in CN and MCI subjects 22 . Impulse dyscontrol is common in advance of dementia, and is an MBI domain that is clinically meaningful 23–25 . Socially inappropriate behaviours are frequent in prodromal AD 26 .…”

Neuropsychiatric symptoms and cerebrovascular risk in non‐demented elders: cross‐sectional study using the mild behavioural impairment checklist (MBI‐C)

“…reported that impulse dyscontrol was strongly correlated with atrophy of mesial temporal regions, which have been early implicated in the trajectory of AD. And another recent study conducted by Gill et al 49 . detected association of impulse dyscontrol with changes of white matter integrity in tracts including the cingulum, fornix, superior fronto‐occipital fasciculus, and uncinate fasciculus.…”

Plasma β-amyloid in mild behavioural impairment – neuropsychiatric symptoms on the Alzheimer’s continuum

“…MBI has several biological correlates, which the literature is just beginning to explore. Known associations exist between MBI and biological markers of AD, including Aβ-positron emission tomography (PET), 16 cerebrospinal fluid (CSF) tau and tau-PET, 38,39 white matter atrophy, 40,41 grey matter atrophy, 42,43 plasma neurofilament light (NfL), 15 and AD risk gene loci. 44,45 The current study extends the literature on the biological basis of MBI.…”

“…Several longitudinal studies have identified emergent impulse dyscontrol symptoms among the earliest behavioural changes associated with incident cognitive decline and dementia. 31,61,62 Two studies found that impulse dyscontrol symptoms were comparable to hippocampal atrophy for prognostication of cognitive decline and dementia, 41,63 associated with both grey and white matter changes in advance of dementia. 40 Thus, the link between AD biomarkers and MBI subdomains can be challenging to interpret, and further investigation is required to explore these relationships.…”