Agitation and impulsivity in mid and late life as possible risk markers for incident dementia

Bateman, Daniel R.; Gill, Sascha; Hu, Sophie; Foster, Erin D.; Ruthirakuhan, Myuri; Sellek, Allis F; Mortby, Moyra E.; Matušková, Veronika; Ng, Kok Pin; Tarawneh, Rawan; Freund‐Levi, Yvonne; Kumar, Sanjeev; Gauthier, Serge; Rosenberg, Paul B.; Oliveira, Fabricio Ferreira de; Devanand, Devangere P.; Ballard, Clive; Ismail, Zahinoor

doi:10.1002/trc2.12016

Cited by 30 publications

(29 citation statements)

References 211 publications

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“…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 ). NPS may emerge before detectable cognitive decline and are associated with a higher risk of clinical progression to mild cognitive impairment (MCI) or dementia ( Sugarman et al, 2018 ; Wise et al, 2019 ).…”

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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“…Thus, we find these results to be in concordance with the findings by Gatchel et al reporting depressive symptoms related to temporal tau deposition 35 and by Ramakers et al reporting anxiety associated with CSF total tau 36 . Impulse dyscontrol and agitation have lately attracted research interest as potential early markers of dementia in mid and late life 37 . In support of our results, agitation and aggression have previously been linked to core AD CSF biomarkers 38 .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Mild behavioral impairment (MBI) is suggested as risk marker for neurodegenerative diseases, such as Alzheimer’s disease (AD). Recently, pathologic tau deposition in the brain has been shown closely related to clinical manifestations, such as cognitive deficits. Yet, associations between tau pathology and MBI have rarely been investigated. It is further debated if MBI precedes cognitive deficits in AD. Here, we explored potential mechanisms by which MBI is related to AD, this by studying associations between MBI and tau in preclinical AD. In all, 50 amyloid-β-positive cognitively unimpaired subjects (part of the BioFINDER-2 study) underwent MBI-checklist (MBI-C) to assess MBI, and the Alzheimer’s Disease Assessment Scale – Cognitive subscale (ADAS-Cog) delayed word recall (ADAS-DR) to assess episodic memory. Early tau pathology was determined using tau-PET ([18F]RO948 retention in entorhinal cortex/hippocampus) and cerebrospinal fluid (CSF) P-tau181. Regression models were used to test for associations. We found that higher tau-PET signal in the entorhinal cortex/hippocampus and CSF P-tau181 levels were associated with higher MBI-C scores (β = 0.010, SE = 0.003, p = 0.003 and β = 1.263, SE = 0.446, p = 0.007, respectively). When MBI-C and ADAS-DR were entered together in the regression models, tau-PET (β = 0.009, p = 0.009) and CSF P-tau181 (β = 0.408, p = 0.006) were predicted by MBI-C, but not ADAS-DR. We conclude that in preclinical AD, MBI is associated with tau independently from memory deficits. This denotes MBI as an important early clinical manifestation related to tau pathology in AD.

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“…Recent evidence also suggests that assessment of NPS such as apathy, mood disturbances, anxiety, agitation, disinhibition, and psychosis may provide a simple and efficient method to identify a high-risk population for dementia [30,31]. Population-based [7,32] as well as clinic-based cohort [33] studies provide consistent evidence that NPS in MCI are associated with higher risk for incident dementia, with an estimated annual rate of progression to dementia of 25% for MCI plus NPS in contrast to 10-15% per year for MCI alone [33,34].…”

Section: Discussionmentioning

confidence: 99%

Using Machine Learning to Predict Dementia from Neuropsychiatric Symptom and Neuroimaging Data

Gill

Mouchès

et al. 2020

JAD

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Background: Machine learning (ML) is a promising technique for patient-specific prediction of mild cognitive impairment (MCI) and dementia development. Neuropsychiatric symptoms (NPS) might improve the accuracy of ML models but have barely been used for this purpose. Objectives: To investigate if baseline mild behavioral impairment (MBI) status used for NPS quantification along with brain morphology features are predictive of follow-up diagnosis, median 40 months later in patients with normal cognition (NC) or MCI. Method: Baseline neuroimaging, neuropsychiatric, and clinical data from 102 individuals with NC and 239 with MCI were extracted from the Alzheimer's Disease Neuroimaging Initiative database. Neuropsychiatric inventory questionnaire items were transformed to MBI domains using a published algorithm. Diagnosis at latest follow-up was used as the outcome variable and ground truth classification. A logistic model tree classifier combined with information gain feature selection was trained to predict follow-up diagnosis. Results: In the binary classification (NC versus MCI/AD), the optimal ML model required only two features from over 200, MBI total score and left hippocampal volume. These features correctly classified participants as remaining normal or developing cognitive impairment with 84.4% accuracy (area under the receiver operating characteristics curve [ROC-AUC] = 0.86). Seven features were selected for the three-class model (NC versus MCI versus dementia) achieving an accuracy of 58.8% (ROC-AUC=0.73).

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Agitation and impulsivity in mid and late life as possible risk markers for incident dementia

Cited by 30 publications

References 211 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 and its relation to tau pathology in preclinical Alzheimer’s disease

Using Machine Learning to Predict Dementia from Neuropsychiatric Symptom and Neuroimaging Data

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