Mild behavioral impairment linked to progression to Alzheimer's disease and cortical thinning in amnestic mild cognitive impairment

Eun Jin Yoon; Jun-Young Lee; Seyul Kwak; Yu Kyeong Kim

doi:10.3389/fnagi.2022.1051621

Mild behavioral impairment linked to progression to Alzheimer's disease and cortical thinning in amnestic mild cognitive impairment

Front Aging Neurosci. 2023 Jan 4:14:1051621. doi: 10.3389/fnagi.2022.1051621. eCollection 2022.

Authors

Eun Jin Yoon^{1

2}, Jun-Young Lee^{3

4

5}, Seyul Kwak⁶, Yu Kyeong Kim^{2

7}

Affiliations

¹ Memory Network Medical Research Center, Seoul National University, Seoul, South Korea.
² Department of Nuclear Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea.
³ Department of Psychiatry, SMG-SNU Boramae Medical Center, Seoul, South Korea.
⁴ Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
⁵ Department of Medical Device Development, Seoul National University College of Medicine, Seoul, South Korea.
⁶ Department of Psychology, Pusan National University, Busan, South Korea.
⁷ Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Abstract

Background: Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergence of sustained neuropsychiatric symptoms, as an at-risk state for dementia. However, the associations between MBI and a risk of progression to Alzheimer's disease (AD) and its neuroanatomical correlates in mild cognitive impairment (MCI) are still unclear.

Method: A total 1,184 older adults with amnestic MCI was followed for a mean of 3.1 ± 2.0 years. MBI was approximated using a transformation algorithm for the Neuropsychiatric Inventory at baseline. A two-step cluster analysis was used to identify subgroups of individuals with amnestic MCI based on profiles of 5 MBI domain symptoms (decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, abnormal perception/thought content). A Cox regression analysis was applied to investigate differences in the risk of progression to AD between subgroups. A subset of participants (n = 202) underwent 3D T1-weighted MRI scans at baseline and cortical thickness was compared between the subgroups of amnestic MCI patients.

Result: The cluster analysis classified the patients into 3 groups: (1) patients without any MBI domain symptoms (47.4%, asymptomatic group); (2) those with only affective dysregulation (29.4%, affective dysregulation group); (3) those with multiple MBI domain symptoms, particularly affective dysregulation, decreased motivation and impulse dyscontrol (23.2%, complex group). Compared to the asymptomatic group, the complex group was associated with a higher risk of progression to AD (hazard ratio = 2.541 [1.904-3.392], p < 0.001), but the affective dysregulation group was not (1.214 [0.883-1.670], p = 0.232). In cortical thickness analysis, the complex group revealed cortical thinning bilaterally in the inferior parietal, lateral occipital, lateral superior temporal, and frontopolar regions compared with the affective dysregulation group.

Conclusion: The multiple co-occuring MBI domains in individuals with amnestic MCI are associated with a higher risk of progression to AD and cortical thinning in temporal, parietal and frontal areas. These results suggest that evaluation of MBI could be useful for risk stratification for AD and appropriate intervention in MCI individuals.

Keywords: Alzheimer’s disease; cortical thickness; magnetic resonance imaging; mild behavioral impairment; mild cognitive impairment; neuropsychiatric symptoms.