Czech Brain Aging Study (CBAS): prospective multicentre cohort study on risk and protective factors for dementia in the Czech Republic

Sheardová, Kateřina; Vyhnálek, Martin; Nedelská, Zuzana; Laczó, Jan; Andel, Ross; Marciniak, Rafał; Cerman, Jiří; Lerch, Ondřej; Hort, Jakub

doi:10.1136/bmjopen-2019-030379

Cited by 36 publications

(39 citation statements)

References 58 publications

(40 reference statements)

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“…A total of 116 participants with subjective cognitive concerns were included in this study. Participants were recruited from the Czech Brain Aging Study (CBAS), an ongoing longitudinal memory clinic-based study aimed at detecting early changes associated with pathological brain aging ( Sheardova et al, 2019 ). Participants with subjectively perceived cognitive complaints were referred to our memory clinic by general practitioners or other specialists.…”

Section: Methodsmentioning

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: Methodsmentioning

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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“…Use of the MBI-C would also allow appropriate examination in pre-dementia populations of MBI domain specific associations with NfL. The MBI-C is being incorporated into some cohorts (COMPASS-ND Canada [51], PROTECT-UK [12], CatchCog -Netherlands [52], BHR -USA [53], CobTek -France [54], Czech Brain Aging Study-Czech Republic [55], Swedish BioFINDER2 [56]), although data will only emerge slowly. In the meantime, our best approach to explore the association of pre-dementia NPS and dementia biomarkers is to use existing datasets to determine if there are signals, which can be explored further.…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment

Naude

Gill

et al. 2020

JAD

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Background: Assessing neuropsychiatric symptoms (NPS) in older adults is important for determining dementia risk. Mild behavioral impairment (MBI) is an at-risk state for cognitive decline and dementia, characterized by emergent NPS in later life. MBI has significantly higher dementia incidence than late life psychiatric conditions. However, its utility as a proxy for neurodegeneration has not been demonstrated. Plasma neurofilament light (NfL) is a validated biomarker of axonal damage, and has been shown to associate with hallmarks of neurodegeneration. Objective: The purpose of this investigation was to identify associations between NfL rate of change and the presence of MBI symptomatology. Methods: We evaluated the association of MBI with changes in NfL in a cohort (n = 584; MBI + n = 190, MBIn = 394) of non-demented participants from the Alzheimer's Disease Neuroimaging Initiative. MBI was determined by transforming Neuropsychiatric Inventory Questionnaire items using a published algorithm. Change in NfL was calculated over 2 years. Results: Time*MBI status was the only significant interaction to predict change in NfL concentrations (F(1,574) = 4.59, p = 0.032), even after controlling for age, mild cognitive impairment, and demographics. Analyses reclassifying 64 participants with new onset MBI over 2 years similarly demonstrated greater increases in NfL (F(1,574) = 5.82, p = 0.016).

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“…CSF samples were obtained by lumbar puncture with collection and storage of the samples carried out according to a well-established internationally recognized consensus protocol 43,45,47 . CSF samples found to be diagnostically unclear or contaminated with blood were excluded from the study.…”

Section: Tissue Collectionmentioning

confidence: 99%

Pathogenesis of Alzheimer’s disease: Involvement of the Choroid Plexus

Čarná

Onyango

Katina

et al. 2021

Preprint

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Alzheimer's disease is a neurodegenerative disorder characterized clinically by cognitive decline and pathologically by amyloid deposition and neurofibrillary changes. These neuropathological hallmarks are accompanied by reactive events including microglial activation and astrogliosis. The inflammatory response in Alzheimer's disease brains is distinguished by a pro-inflammatory signature involving amyloid peptides, inflammasome signalling and disrupted blood brain barrier. Inflammatory changes are observed also in the cerebrospinal fluid in Alzheimer's disease. It remains unknown, however, whether the choroid plexus which produces cerebrospinal fluid and guards the brain from peripheral inflammatory insults, contributes to the inflammation and pathogenesis of Alzheimer's disease. Here we show that the choroid plexus in Alzheimer's disease exhibits a pro-inflammaotory signature with aberrant protein accumulation, which contribute to the age-dependent inflammatory changes observed in the cerebrospinal fluid. Magnetic resonance imaging reveals that the choroid plexus in patients with Alzheimer's disease displays pathological signal and increased volume, which inversely correlates with cognitive decline. Our findings suggest that the choroid plexus, being unable to efficiently resolve inflammatory insults over the lifetime, eventually ignites and drives the aberrant inflammatory response observed in Alzheimer's disease. These findings advance our understanding of the pathogenesis and open new vistas in the diagnostics and therapeutics of Alzheimer's disease.

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Czech Brain Aging Study (CBAS): prospective multicentre cohort study on risk and protective factors for dementia in the Czech Republic

Cited by 36 publications

References 58 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

Plasma Neurofilament Light: A Marker of Neurodegeneration in Mild Behavioral Impairment

Pathogenesis of Alzheimer’s disease: Involvement of the Choroid Plexus

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