Genetic risk for Alzheimer's disease, cognition, and mild behavioral impairment in healthy older adults

Creese, Byron; Arathimos, Ryan; Brooker, Helen; Aarsland, Dag; Corbett, Anne; Lewis, Cathryn M.; Ballard, Clive; Ismail, Zahinoor

doi:10.1002/dad2.12164

Cited by 39 publications

(46 citation statements)

References 51 publications

(128 reference statements)

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“…The presence of MBI in non-demented ADNI participants predicted a higher increase in a plasma neurofilament light protein over 2 years compared to the participants without MBI, bringing evidence for the link between MBI and subsequent neurodegeneration ( Naude et al, 2020 ). Furthermore, MBI has demonstrated an association with AD risk genes ( Andrews et al, 2018 ; Creese et al, 2021 ). Thus, it seems that MBI also identifies a potential at-risk group for incident cognitive decline and AD dementia.…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…In a sample of over 4000 people stratified by MBI status, AD genetic risk was associated with cognitive performance in those with MBI but not in those without. These findings suggest screening on MBI may enrich samples for a cognitive phenotype associated with AD biomarkers [31]. While encouraging, no firm conclusions can be drawn about the etiology underlying genetic and cognitive associations.…”

Section: Mainmentioning

confidence: 96%

Mild behavioral impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease

Creese

Ismail

2022

Alz Res Therapy

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Background Late-life onset neuropsychiatric symptoms are established risk factors for dementia. The mild behavioral impairment (MBI) diagnostic framework was designed to standardize assessment to determine dementia risk better. In this Mini Review, we summarize the emerging clinical and biomarker evidence, which suggests that for some, MBI is a marker of preclinical Alzheimer’s disease. Main MBI is generally more common in those with greater cognitive impairment. In community and clinical samples, frequency is around 10–15%. Mounting evidence in cognitively normal samples links MBI symptoms with known AD biomarkers for amyloid, tau, and neurodegeneration, as well as AD risk genes. Clinical studies have found detectable differences in cognition associated with MBI in cognitively unimpaired people. Conclusion The emerging evidence from biomarker and clinical studies suggests MBI can be an early manifestation of underlying neurodegenerative disease. Future research must now further validate MBI to improve identification of those at the very earliest stages of disease.

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“…The pathophysiological process of AD begins years before the diagnosis of clinical dementia 3 . Recent research shows that neuropsychiatric symptoms (NPS) or mild behavioural impairment (MBI) could be early manifestations of neurodegenerative disease 4–12 …”

Section: Introductionmentioning

confidence: 99%

Prevalence of mild behavioural impairment domains: a meta‐analysis

et al. 2021

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Background Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta‐analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. Methods A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta‐analysis using a random effects model and meta‐regression was performed. Results Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta‐analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44–42.5%), 26.67% (95% CI 18.24–37.23%), 12.58% (95% CI 6.93–21.75%), 6.05% (95% CI 3.44–10.42%), and 2.81% (95% CI 1.67–4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta‐regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. Conclusions AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.

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Genetic risk for Alzheimer's disease, cognition, and mild behavioral impairment in healthy older adults

Cited by 39 publications

References 51 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

Mild behavioral impairment: measurement and clinical correlates of a novel marker of preclinical Alzheimer’s disease

Prevalence of mild behavioural impairment domains: a meta‐analysis

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