Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer’s disease

Johansson, Maurits; Stomrud, Erik; Insel, Philip S.; Leuzy, Antoine; Johansson, Per; Smith, Ruben; Ismail, Zahinoor; Janelidze, Shorena; Palmqvist, Sebastian; Westen, Danielle van; Mattsson‐Carlgren, Niklas; Hansson, Oskar

doi:10.1038/s41398-021-01206-z

Cited by 98 publications

(115 citation statements)

References 38 publications

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“…We found impulse dyscontrol domain to be the most strongly associated with MTL atrophy. This complies with a very recent finding that impulse dyscontrol was associated with tau deposition in the ERC and hippocampus in preclinical AD ( Johansson et al, 2021 ). Also, an ADNI machine learning study found that baseline presence of these symptoms was an important input feature for cognitive category classification (CN, MCI, and dementia) at 40 months ( Gill et al, 2020 ).…”

Section: Discussionsupporting

confidence: 93%

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

Matušková

Ismail²,

Nikolai³

et al. 2021

Front. Aging Neurosci.

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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.

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Section: Discussionsupporting

confidence: 93%

“…Our findings are therefore consistent with prior reports describing MBI as a manifestation of neurodegeneration ( Ismail et al, 2016 ) and, in some, a manifestation of early AD. The latter is also supported by research linking MBI to AD pathology in cognitively normal older adults ( Lussier et al, 2020 ; Johansson et al, 2021 ).…”

Section: Discussionmentioning

confidence: 75%

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

Matušková

Ismail²,

Nikolai³

et al. 2021

Front. Aging Neurosci.

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“…A recent study found that MBI scores were associated with global and striatal amyloid-PET signal, but not with tau-PET signal [11]. Conversely, another study showed that MBI scores were associated with higher tau-PET signal in the entorhinal cortex/hippocampus [10]. This discrepancy could be attributed to diverse populations.…”

Section: Introductionmentioning

confidence: 95%

“…Two five-year longitudinal follow-up studies reported that about 70% of patients with MBI eventually progressed to dementia and MBI patients with MCI were more likely to develop Alzheimer's dementia (AD), whereas MBI patients without MCI were more likely Ivyspring International Publisher to convert into frontotemporal dementia(FTD) [4,8]. Lately, some biomarkers of neurodegenerative disease including neurofilament light [9], tau [10], and amyloid [11]; and genetic risk for AD [12] in cognitively normal samples were found to associate with MBI. A recent study found that MBI scores were associated with global and striatal amyloid-PET signal, but not with tau-PET signal [11].…”

Section: Introductionmentioning

confidence: 99%

Distinct Patterns of Brain Atrophy associated with Mild Behavioral Impairment in Cognitively Normal Elderly Adults

et al. 2021

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A cross-sectional study was conducted to evaluate patterns of gray matter changes in cognitively normal elderly adults with mild behavioral impairment (MBI). Sixteen MBI patients and 18 healthy controls were selected. All the participants underwent a neuropsychological assessment battery, including the Mini-mental State Examination (MMSE), Geriatric Depression Scale (GDS), Self-rating Anxiety Scale (SAS), and Chinese version of the mild behavioral impairment-checklist scale (MBI-C), and magnetic resonance imaging (MRI) scans. Imaging data was analyzed based on voxel-based morphometry (VBM). There was no significant difference in age, gender, MMSE score, total intracranial volume, white matter hyperdensity, gray matter volume, white matter volume between the two groups (p > 0.05). MBI group had shorter education years and higher MBI-C score, GDS and SAS scores than the normal control group (p < 0.05). For neuroimaging analysis, compared to the normal control group, the MBI group showed decreased volume in the left brainstem, right temporal transverse gyrus, left superior temporal gyrus, left inferior temporal gyrus, left middle temporal gyrus, right occipital pole, right thalamus, left precentral gyrus and left middle frontal gyrus(uncorrected p < 0.001). The grey matter regions correlated with the MBI-C score included the left postcentral gyrus, right exterior cerebellum, and left superior frontal gyrus. This suggests a link between MBI and decreased grey matter volume in cognitively normal elderly adults. Atrophy in the left frontal cortex and right thalamus in MBI patients is in line with frontal-subcortical circuit deficits, which have been linked to neuropsychiatric symptoms (NPS) in dementia. These initial results imply that MBI might be an early harbinger for subsequent cognitive decline and dementia.

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“…As such, the features of MCD differ from those of singledomain aMCI and of multiple-domain aMCI, which was thought to be characterized by deficits in episodic memory and one or more other cognitive domains [19]. Moreover, the MCD criteria do not correspond with those of mild behavioral impairment (MBI) which is characterized by persistent behavioral symptoms in late life and is thought to constitute a risk for neurodegenerative disease [34,35]. Indeed, in our study the MCD group did not display any behavioral or social dysfunctions.…”

Section: Mild Cognitive Dysfunctions (Mcd) As An Intermediate Classmentioning

confidence: 99%

Mild Cognitive Impairment is not a Valid Concept and Should be Replaced by a More Restrictive, Biologically Validated Class, Named Mild Cognitive Dysfunctions (MCD): A Nomothetic Network Approach

Maes¹,

Tangwongchai²

2021

Preprint

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Background: No studies have examined whether interactions between the apolipoprotein E4 (ApoE4) allele and peripheral biomarkers, hypertension, and type 2 diabetes mellitus (T2DM) may impact the neurocognitive, behavioral and social dysfunctions in amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD). Aims: To clinically define and biologically validate a subgroup of aMCI subjects that take up an intermediate position between controls and AD patients. Methods: In 61 healthy controls, 60 subjects with aMCI, and 60 AD patients we measured the features of aMCI/AD using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). A composite BIORISK score was computed using the ApoE4 allele, serum folate, albumin, white blood cells, fasting blood glucose (FBG), atherogenic index of plasma (AIP), T2DM and hypertension. Results: Clustering and nearest neighbour analyses were unable to validate the aMCI subgroup. We constructed two z unit-based composite scores, the first indicating overall burden of cognitive, social, and behavioural deterioration (OBD), and a second reflecting the interactions between ApoE4, all other biomarkers, hypertension and T2DM (BIORISK). We found that 40.2% of the variance in the OBD score was explained by BIORISK, ApoE4, age and education. The OBD index was used to construct three subgroups (normal, medium, and high OBD) with the medium group (n=45) showing mild cognitive dysfunctions (MCD) in memory, language, orientation, and ADL. People with MCD show OBD and BIORISK scores that are significantly different from controls and AD.Conclusions: Petersen’s aMCI criteria cannot be validated and should be replaced by the more restrictive, biologically validated MCD class.

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Mild behavioral impairment and its relation to tau pathology in preclinical Alzheimer’s disease

Cited by 98 publications

References 38 publications

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

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

Distinct Patterns of Brain Atrophy associated with Mild Behavioral Impairment in Cognitively Normal Elderly Adults

Mild Cognitive Impairment is not a Valid Concept and Should be Replaced by a More Restrictive, Biologically Validated Class, Named Mild Cognitive Dysfunctions (MCD): A Nomothetic Network Approach

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