Dataset Information

Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia-free older adults.

ABSTRACT:

Background

The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers.

Methods

Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed-effects models.

Results

The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation.

Discussion

Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment.

Highlights

Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p. pTau could be a pharmacological target to treat agitation and psychosis symptoms. MBI domains were linked to metabolic dysregulation involving insulin and homocysteine.

SUBMITTER: Gonzalez-Bautista E

PROVIDER: S-EPMC11247706 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia-free older adults.

Gonzalez-Bautista Emmanuel E Momméja Marie M de Mauléon Adelaïde A Ismail Zahinoor Z Vellas Bruno B Delrieu Julien J Soto Martin Maria E ME

Alzheimer's & dementia : the journal of the Alzheimer's Association 20240614 7

<h4>Background</h4>The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers.<h4>Methods</h4>Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tes ...[more]

PMID: 38877658

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Project description:BackgroundMild behavioral impairment (MBI) is a syndrome that uses later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a group at high risk for incident dementia. MBI is associated with neurodegenerative disease markers in advance of syndromic dementia. Functional connectivity (FC) correlates of MBI are understudied and could provide further insights into mechanisms early in the disease course. We used resting-state functional magnetic resonance imaging (rs-fMRI) to test the hypothesis that FC within the default mode network (DMN) and salience network (SN) of persons with MBI (MBI+) is reduced, relative to those without (MBI-).MethodsFrom two harmonized dementia-free cohort studies, using a score of ≥6 on the MBI Checklist to define MBI status, 32 MBI+ and 63 MBI- individuals were identified (mean age: 71.7 years; 54.7% female). Seed-based connectivity analysis was implemented in each MBI group using the CONN fMRI toolbox (v20.b), with the posterior cingulate cortex (PCC) as the seed region within the DMN and anterior cingulate cortex (ACC) as the seed within the SN. The average time series from the PCC and ACC were used to determine FC with other regions within the DMN (medial prefrontal cortex, lateral inferior parietal cortex) and SN (anterior insula, supramarginal gyrus, rostral prefrontal cortex), respectively. Age, sex, years of education, and Montreal Cognitive Assessment scores were included as model covariates. The false discovery rate approach was used to correct for multiple comparisons, with a p-value of .05 considered significant.ResultsFor the DMN, MBI+ individuals exhibited reduced FC between the PCC and the medial prefrontal cortex, compared to MBI-. For the SN, MBI+ individuals exhibited reduced FC between the ACC and left anterior insula.ConclusionMBI in dementia-free older adults is associated with reduced FC in networks known to be disrupted in dementia. Our results complement the evidence linking MBI with Alzheimer's disease biomarkers.HighlightsResting-state functional magnetic resonance imaging was completed in 95 dementia-free persons from FAVR and COMPASS-ND studies.Participants were stratified by informant-rated Mild Behavioral Impairment Checklist (MBI-C) score, ≥6 for MBI+.MBI+ participants showed reduced functional connectivity (FC) within the default mode network and salience network.These FC changes are consistent with those seen in early-stage Alzheimer's disease.MBI may help identify persons with early-stage neurodegenerative disease.

Project description:ObjectiveThis study investigated associations of prior head injury and number of prior head injuries with mild behavioral impairment (MBI) domains.SettingThe Atherosclerosis Risk in Communities (ARIC) Study.ParticipantsA total of 2534 community-dwelling older adults who took part in the ARIC Neurocognitive Study stage 2 examination were included.DesignThis was a prospective cohort study. Head injury was defined using self-reported and International Classification of Diseases, Ninth Revision ( ICD -9) code data. MBI domains were defined using the Neuropsychiatric Inventory Questionnaire (NPI-Q) via an established algorithm mapping noncognitive neuropsychiatric symptoms to the 6 domains of decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content.Main measuresThe primary outcome was the presence of impairment in MBI domains.ResultsParticipants were a mean age of 76 years, with a median time from first head injury to NPI-Q administration of 32 years. The age-adjusted prevalence of symptoms in any 1+ MBI domains was significantly higher among individuals with versus without prior head injury (31.3% vs 26.0%, P = .027). In adjusted models, a history of 2+ head injuries, but not 1 prior head injury, was associated with increased odds of impairment in affective dysregulation and impulse dyscontrol domains, compared with no history of head injury (odds ratio [OR] = 1.83, 95% CI = 1.13-2.98, and OR = 1.74, 95% CI = 1.08-2.78, respectively). Prior head injury was not associated with symptoms in MBI domains of decreased motivation, social inappropriateness, and abnormal perception/thought content (all P > .05).ConclusionPrior head injury in older adults was associated with greater MBI domain symptoms, specifically affective dysregulation and impulse dyscontrol. Our results suggest that the construct of MBI can be used to systematically examine the noncognitive neuropsychiatric sequelae of head injury; further studies are needed to examine whether the systematic identification and rapid treatment of neuropsychiatric symptoms after head injury is associated with improved outcomes.

Project description:IntroductionHearing loss (HL) and mild behavioral impairment (MBI) are non-cognitive markers of dementia. This study investigated the relationship between hearing and MBI and explored the influence of hearing aid use on the treatment of hearing loss, both cross-sectionally and longitudinally.MethodsData were analyzed from National Alzheimer's Coordinating Center participants, age ≥50, dementia-free at baseline, collected between 2005 and 2022. Three self-report questions were used to generate a three-level categorical hearing variable: No-HL, Untreated-HL, and Treated-HL. MBI status was derived from the informant-rated Neuropsychiatric Inventory Questionnaire (NPI-Q) using a published algorithm. At baseline (n = 7080), logistic regression was used to examine the association between hearing status (predictor) and the presence of global and domain-specific MBI (outcome), adjusting for age, sex, cognitive diagnosis, and apolipoprotein E4 (APOE4). Cox proportional hazard models with time-dependent covariates were used to examine the effect of (1) hearing status as exposure on the rate of incident MBI (n = 5889); and (2) MBI as exposure on the rate of incident HL in those with no HL at baseline (n = 6252).ResultsCross-sectionally, participants with Untreated-HL were more likely to exhibit global MBI (adjusted odds ratio (aOR) = 1.66, 95% CI: 1.24-2.21) and individual MBI domains of social inappropriateness (aOR = 1.95, 95% CI: 1.06-3.39), affective dysregulation (aOR = 1.71, 95% CI: 1.21-2.38), and impulse dyscontrol (aOR = 1.71, 95% CI: 1.21-2.38), compared to those with No-HL. Participants with Treated-HL (i.e., hearing aid use) did not differ from No-HL for odds of global or most MBI domains, except for impulse dyscontrol (aOR = 1.38, 95% CI: 1.05-1.81). Longitudinally, we found relationships between Treated-HL and incident MBI (adjusted hazard ratio (aHR) = 1.29, 95% CI: 1.01-1.63) and between MBI and incident Untreated-HL (aHR = 1.51, 95% CI: 1.19-1.94).DiscussionOur cross-sectional results support that hearing aid use is associated with lower odds of concurrent global MBI in dementia-free participants. Longitudinally, relationships were found between MBI and HL. The severity of HL was not assessed, however, and may require further exploration.HighlightsHearing Loss (HL) and mild behavioral impairment (MBI) are markers of dementiaCross-sectionally: Untreated-HL was associated with global MBI burden, butHL treated with hearing aids was notWe found associations between MBI and incident Untreated-HL.

Project description:IntroductionTraumatic brain injury (TBI) may alter dementia progression, although co-occurring neuropsychiatric symptoms (NPS) have received less attention. Originally designed to evaluate behavioral disruption prior to dementia diagnosis, the mild behavioral impairment (MBI) construct relates NPS to underlying neural circuit disruptions, with probable relevance across the progression of neurodegenerative disease. Therefore, the MBI construct may represent a valuable tool to identify and evaluate related NPS both preceding diagnosis of all-cause dementia throughout the progression of disease, representing an important area of inquiry regarding TBI and dementia. This investigation sought to evaluate the effect of TBI on NPS related by the MBI construct in participants progressing from normal cognitive status to all-cause dementia.MethodsUsing National Alzheimer's Coordinating Center data, individuals progressing from normal cognition to all-cause dementia (clinician diagnosed) over 7.6 ± 3.0 years were studied to estimate prevalence of MBI domains in 124 participants with prior TBI history (57 with loss of consciousness [LOC] <5 minutes, 22 with LOC >5 min, 45 unknown severity) compared to 822 without. MBI domain prevalence was evaluated (1) prior to dementia onset (including only time points preceding time at dementia diagnosis, as per MBI's original definition) and (2) throughout dementia progression (evaluating all available time points, including both before and after dementia diagnosis).ResultsMore severe TBI (LOC >5 minutes) was associated with the social inappropriateness MBI domain (adjusted odds ratio = 4.034; P = 0.024) prior to dementia onset, and the abnormal perception/thought content domain looking across dementia progression (adjusted hazard ratio [HRadj] = 3.703; P = 0.005). TBI (all severities) was associated with the decreased motivation domain looking throughout dementia progression (HRadj. = 1.546; P = 0.014).DiscussionTBI history is associated with particular MBI profiles prior to onset and throughout progression of dementia. Understanding TBI's impact on inter-related NPS may help elucidate underlying neuropathology with implications for surveillance, detection, and treatment of behavioral concerns in aging TBI survivors.HighlightsThe mild behavioral impairment (MBI) construct links related neuropsychiatric symptoms (NPS) by probable underlying neural network dysfunction.Traumatic brain injury (TBI) with loss of consciousness (LOC) > 5 minutes was associated with pre-dementia social inappropriateness.TBI was associated with decreased motivation looking across dementia progression.TBI with LOC > 5 minutes was associated with abnormal perception/thought content.The MBI construct may be useful for examining related NPS across dementia progression.

Project description:Mild behavioral impairment (MBI) is a high-risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) in dementia but can also develop in persons with normal cognition (NC) or mild cognitive impairment (MCI). The later-life emergence and persistence of apathy as part of the MBI syndrome may be a driving factor for dementia risk. Therefore, we investigated MBI-apathy-associated progression to dementia, and effect modification by sex, race, cognitive diagnosis, and apolipoprotein E (APOE) genotype. Dementia-free National Alzheimer's Coordinating Center participants were stratified by persistent apathy status, based on Neuropsychiatric Inventory (NPI)-Questionnaire scores at two consecutive visits. Hazard ratios (HRs) for incident dementia for MBI-apathy and NPI-apathy relative to no NPS, and MBI-apathy relative to no apathy, were determined using Cox proportional hazards regressions, adjusted for baseline age, sex, years of education, race, cognitive diagnosis, and APOE genotype. Interactions with relevant model covariates were explored. Of the 3932 participants (3247 with NC), 354 had MBI-apathy. Of all analytic groups, MBI-apathy had the greatest dementia incidence (HR = 2.69, 95% confidence interval [CI]: 2.15-3.36, P < 0.001). Interaction effects were observed between cognitive diagnosis and APOE genotype with the NPS group. The contribution of apathy to dementia risk was greater in NC (HR = 5.91, 95% CI: 3.91-8.93) than in MCI (HR = 2.16, 95% CI: 1.69-2.77, interaction P < 0.001) and in all APOE genotypes, was greatest in APOE ɛ3 (HR = 4.25, 95% CI: 3.1-5.82, interaction P < 0.001). Individuals with MBI-apathy have a markedly elevated risk for future dementia, especially when symptoms emerge in those with NC. Both cognitive status and APOE genotype are important moderators in the relationship between MBI-apathy and incident dementia. MBI-apathy may represent a group in whom apathy is a preclinical or prodromal manifestation of dementia and identify a precision medicine target for preventative interventions.

Project description:BackgroundAttention is essential to daily life and cognitive functioning, and attention deficits can affect daily functional and social behaviour, such as falls, risky driving, and accidental injuries. However, attention function is important yet easily overlooked in older adults with mild cognitive impairment, and evidence is limited. We aimed to explore the pooled effect of cognitive training on domains of attention in older adults with mild cognitive impairment and mild dementia using a meta-analysis of randomised controlled trials.MethodsWe searched PubMed, Embase, Scopus, Web of Science, CINAHL, PsycINFO, and Cochrane Library for randomised controlled trials (RCTs) up to 3 November 2022. We included participants aged ≥50 years diagnosed with cognitive impairment, with various cognitive training interventions as the intervention measures. The primary outcome was overall attention and the secondary outcomes were attention in different domains and global cognitive function. We calculated the Hedges' g and confidence intervals (CIs) using a random-effects model to evaluate the effect size of the outcome measures and evaluated heterogeneity using the χ2 test and I2 value.ResultsWe included 17 RCTs and found that cognitive training interventions improve overall attention (Hedges' g = 0.41; 95% CI = 0.13, 0.70), selective attention (Hedges' g = 0.37; 95% CI = 0.19, 0.55), divided attention (Hedges' g = 0.38; 95% CI = 0.03, 0.72), and global cognitive function (Hedges' g = 0.30; 95% CI = 0.02, 0.58) in older adults with mild cognitive impairment, but with relatively low effectiveness.ConclusionsCognitive training intervention can improve some attention functions in older adults with mild cognitive impairment. Attention function training should also be incorporated into routine activities and long-term sustainability planning to delay the deterioration of attention function in older adults. Besides reducing their risk of abnormal events in daily life (such as falls), it can also improve their quality of life and help reduce the progression of cognitive impairment, achieving early detection of secondary prevention.RegistrationPROSPERO (CRD42022385211).

Dataset Information

Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia-free older adults.

Background

Methods

Results

Discussion

Highlights

Publications

Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia-free older adults.

Similar Datasets

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