Mild Behavioral Impairment Is Associated With Atrophy of Entorhinal Cortex and Hippocampus in a Memory Clinic Cohort.

Veronika Matuskova,Katerina Cechova,Zahinoor Ismail,Meng Wang,Martin Vyhnalek,Jan Laczó,Tomas Nikolai,Hana Markova,Jakub Hort,Zuzana Nedelska

doi:10.3389/fnagi.2021.643271

Abstract

ObjectivesMild behavioral impairment (MBI) is a syndrome describing late-onset persistent neuropsychiatric symptoms (NPS) in non-demented older adults. Few studies to date have investigated the associations of MBI with structural brain changes. Our aim was to explore structural correlates of NPS in a non-demented memory clinic sample using the Mild Behavioral Impairment Checklist (MBI-C) that has been developed to measure MBI.MethodsOne hundred sixteen non-demented older adults from the Czech Brain Aging Study with subjective cognitive concerns were classified as subjective cognitive decline (n = 37) or mild cognitive impairment (n = 79). Participants underwent neurological and neuropsychological examinations and brain magnetic resonance imaging (MRI) (1.5 T). The Czech version of the MBI-C was administered to participants’ informants. Five a priori selected brain regions were measured, namely, thicknesses of the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and entorhinal cortex (ERC) and volume of the hippocampus (HV), and correlated with MBI-C total and domain scores.ResultsEntorhinal cortex was associated with MBI-C total score (rS = −0.368, p < 0.001) and with impulse dyscontrol score (rS = −0.284, p = 0.002). HV was associated with decreased motivation (rS = −0.248, p = 0.008) and impulse dyscontrol score (rS = −0.240, p = 0.011).ConclusionNeuropsychiatric symptoms, particularly in the MBI impulse dyscontrol and motivation domains, are associated with medial temporal lobe atrophy in a clinical cohort of non-demented older adults. This study supports earlier involvement of temporal rather than frontal regions in NPS manifestation. Since these regions are typically affected early in the course of Alzheimer’s disease (AD), the MBI-C may potentially help further identify individuals at-risk of developing AD dementia.

Highlights

Neuropsychiatric symptoms (NPS) are a common feature in early stages of various neurodegenerative diseases (Desmarais et al, 2018; Fischer and Agüera-Ortiz, 2018; Ismail et al, 2018; Sherman et al, 2018; Bateman et al, 2020) and can precede the onset of dementia by several years (Singh-Manoux et al, 2017; Tapiainen et al, 2017)
Within mild behavioral impairment (MBI)-C domains, impulse dyscontrol score was moderately associated with ERC thickness and weakly associated with hippocampal volumes (HV), the former remaining significant after additional controlling for Mini-Mental State Examination (MMSE)
Decreased motivation score was weakly associated with HV; this association disappeared after additional controlling for MMSE

Summary

Introduction

Neuropsychiatric symptoms (NPS) are a common feature in early stages of various neurodegenerative diseases (Desmarais et al, 2018; Fischer and Agüera-Ortiz, 2018; Ismail et al, 2018; Sherman et al, 2018; Bateman et al, 2020) and can precede the onset of dementia by several years (Singh-Manoux et al, 2017; Tapiainen et al, 2017). There is compelling evidence linking various NPS, such as depression, anxiety, apathy, agitation, and irritability, to accumulation of betaamyloid, a hallmark of Alzheimer’s disease (AD) (Bensamoun et al, 2016; Ng et al, 2017; Gatchel et al, 2019; Goukasian et al, 2019; Johansson et al, 2020), but these symptoms can occur in physiological aging (Bunce et al, 2012) or can be related to other pathologies, such as cerebrovascular disease (Tiel et al, 2015) MBI (assessed with the Neuropsychiatric Inventory) was highly prevalent in both clinical and community-based cohorts of non-demented older adults (Mortby et al, 2018; Sheikh et al, 2018)

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