Mild Behavioral Impairment as a Predictor of Functional Status.

Mild behavioural impairment (MBI) is an emergent and persistent neuropsychiatric symptom (NPS) in subjects aged 50 and older who are at risk for cognitive decline. We examined the prevalence of MBI across the spectrum from cognitively normal (CN), mild cognitive impairment (MCI), to dementia, and further investigated the association between the MBI domain and cognitive and functional impairment. MBI was assessed in 2337 elderly patients in the Alzheimer's Disease Neuroimaging Initiative database (mean age, 73.04 years; 52.8% male). Among the subjects, 868 (37.1%) had normal cognition, 1066 (45.6%) had MCI, and 403 (17.2%) had mild Alzheimer's dementia (AD). MBI was evaluated in accordance with the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment diagnostic criteria for MBI, utilising the Neuropsychiatric Inventory. We compared the prevalence of the MBI domain with CN using multinominal logistic regression analysis and further quantified the magnitude of the association between MCI/AD and the MBI domains by calculating the population attributable risk (PAR). We assessed the association between the MBI domains and cognitive and functional impairment using simultaneous linear regression analysis. The most common MBI domains in each diagnostic group were affective dysregulation followed by impulse dyscontrol, decreased motivation, social inappropriateness, and abnormal perception or thought content. The PARs for MBI domains in subjects with MCI or AD were respectively: 16.60% and 24.34% for affective dysregulation; 3.72% and 18.06% for impulse dyscontrol; 4.78% and 14.13% for decreased motivation, 1.91% and 2.29% for social inappropriateness; and 0.68% and 3.85% for abnormal perception or thought content. All MBI domains except for social inappropriateness were significantly associated with a higher 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale total score. All MBI domains were significantly associated with a higher Functional Activities Questionnaire total score. Our findings show that MBI is highly prevalent across subjects with CN, MCI, and AD and is associated with cognitive and functional decline. MBI could be a crucial clinical phenotype relevant to the risk of cognitive and functional impairment, and provides a useful dimension pertinent to diagnostic approaches.

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. 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. 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. 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.

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).Conclusion:Baseline NPS, categorized for MBI domain and duration, have prognostic utility in addition to brain morphology measures for predicting diagnosis change using ML. MBI total score, followed by impulse dyscontrol and affective dysregulation were most predictive of future diagnosis.

Mild behavioral impairment (MBI) describes persistent behavioral changes in later life as an at-risk state for dementia. While cardiovascular risk factors (CVRFs) are linked to dementia, it is uncertain how CVRFs are associated with MBI. To determine the prevalence of MBI and its association with CVRFs among cognitively normal (CN) and mild cognitive impairment (MCI) individuals in Singapore. 172 individuals (79 CN and 93 MCI) completed the MBI-checklist (MBI-C). The prevalence of MBI and MBI-C sub-domain characteristics among CN and MCI were examined. Regression models evaluated the relationships between MBI-C sub-domain scores with CVRFs. The prevalence of MBI and mean MBI-C total score were significantly higher among MCI than CN (34.4%versus 20.3%, p = 0.022 and 7.01 versus 4.12, p = 0.04). The highest and lowest-rated sub-domains among CN and MCI were impulse dyscontrol and abnormal thoughts and perception respectively. Within the MCI cohort, a higher proportion of individuals with diabetes mellitus (DM) had MBI compared to individuals without DM (28.1%versus 10.4%, p = 0.025). The interaction of DM and MCI cohort resulted in significantly higher mean MBI-C total, decreased motivation, emotional dysregulation, impulse dyscontrol, and abnormal thoughts and perception sub-domain scores. The prevalence of MBI is higher among a Singapore cohort compared to Caucasian cohorts. The associations of DM with both the presence and severity of MBI among MCI suggest that DM may be a risk factor for MBI. The optimization of DM may be a potential therapeutic approach to improve clinical outcomes among MCI with MBI.

Simple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma β-amyloid (Aβ) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aβ42/Aβ40. Participants with normal cognition (n = 86) or mild cognitive impairment (n = 53) were selected from the Alzheimer's Disease Neuroimaging Initiative. MBI scores were derived from Neuropsychiatric Inventory items. Plasma Aβ42/Aβ40 ratios were assayed using mass spectrometry. Linear regressions were fitted to assess the association between MBI total score as well as MBI domain scores with plasma Aβ42/Aβ40. Lower plasma Aβ42/Aβ40 was associated with higher MBI total score (p = 0.04) and greater affective dysregulation (p = 0.04), but not with impaired drive/motivation (p = 0.095) or impulse dyscontrol (p = 0.29) MBI domains. In persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aβ42/Aβ40. Incorporating MBI into case detection may help capture preclinical and prodromal Alzheimer's disease.

ObjectiveTraumatic Brain Injury (TBI) may contribute additional complexity to the clinical picture of mild behavioral impairment (MBI). MBI, a behavioral analog to mild cognitive impairment (MCI), is comprised of five neuropsychiatric domains: decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. We investigated (1) if cross-sectional associations of cognitive status with MBI symptoms differ by TBI status and (2) if prospective associations of MBI domain positivity with incident dementia risk differ by TBI status.Methods2246 participants without dementia from the Atherosclerosis Risk in Communities Study were included (mean age = 75.6years, 59.0% female). TBI was defined by self-report/ICD-9/10 codes, MBI via an established algorithm based on the Neuropsychiatric Inventory Questionnaire, and baseline cognitive status/incident dementia using neuropsychological tests, informant interviews, and hospital/death certificate codes.ResultsCross-sectionally, although MCI status was associated with greater odds of MBI, this did not differ based on TBI status (MCI with TBI: OR = 2.04, 95% CI = 1.44-2.88, MCI without TBI: OR = 1.60, 95% CI = 1.20-2.14). Individuals with MCI (with or without TBI) were more likely to have decreased motivation, affective dysregulation, and impulse dyscontrol. Prospectively, positivity in 1+ MBI domains was associated with increased risk of incident dementia, not differing by TBI status (no TBI and MBI: HR = 2.15, 95% CI = 1.55-2.99, TBI and MBI: HR = 2.62, 95% CI = 1.81-3.80).ConclusionsNeither cross-sectional associations between cognitive status and MBI domain positivity nor prospective associations of MBI domain positivity with incident dementia risk differed by TBI status. How TBI may relate to neuropsychiatric symptomatology in the context of neurodegenerative processes requires further clarification.

BackgroundMild Behavioural Impairment (MBI), an “at risk” state for incident cognitive declin, is characterized by late onset, sustained neuropsychiatric symptoms of any severity which cannot be accounted for by other formal medical and psychiatric nosology. There is no study related to MBI from India.Methods and findingsIn this cross-sectional observational study 124 subjects 60 years and above were recruited between March 2017 to October 2018, from memory clinic of department of Geriatric medicine with memory or behavioural complains. Subjects with major neurocognitive impairment (CDR score of 1 or more), major depressive disorder, generalized anxiety disorder and impaired activities of daily living (ADL) were excluded. Subjects with Mild Cognitive impairment (MCI) (CDR- 0.5), and Subjective cognitive impairment (SCI) (CDR- 0) were included. Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to identify the presence of NPS. The ISTAART-MBI (International Society of Advance Alzheimer’s Research and Treatment-Alzheimer’s Association) diagnostic criteria was used to diagnose MBI. All the participants underwent a geriatric assessment using standardised screening. The objectives of this study was to determine the frequency of mild behavioural impairment (MBI), and its domains, in MCI or SCI and its association with comorbidities and geriatric syndromes. The mean age of the participants was 69.21, 71.77% (89) were male and 28.23% (35) were female. 41.13% (51) of these individuals were diagnosed with MBI. The MBI and non MBI group differed significantly in marital status, cognitive status and MCI subtype. The proportion of domains involved are as follows: decreased motivation 60.78%(31), emotional dysregulation 54.90% (28), impulse dyscontrol 68.63% (35), social inappropriateness 21.57%(11), abnormal perception 2 (3.93%). Presence of multi-morbidity, and diabetes, were statistically significant between the groups.ConclusionThis study presents the first clinic-based prevalence estimates of MBI from Asia. Findings indicate a relatively high prevalence of MBI in predementia clinical states, impulse dyscontrol was the most commonly involved MBI domain. Multimorbidity, diabetes, urinary incontinence were other determinants of MBI.

Mild Behavioural Impairment (MBI), an "at risk" state for incident cognitive declin, is characterized by late onset, sustained neuropsychiatric symptoms of any severity which cannot be accounted for by other formal medical and psychiatric nosology. There is no study related to MBI from India. In this cross-sectional observational study 124 subjects 60 years and above were recruited between March 2017 to October 2018, from memory clinic of department of Geriatric medicine with memory or behavioural complains. Subjects with major neurocognitive impairment (CDR score of 1 or more), major depressive disorder, generalized anxiety disorder and impaired activities of daily living (ADL) were excluded. Subjects with Mild Cognitive impairment (MCI) (CDR- 0.5), and Subjective cognitive impairment (SCI) (CDR- 0) were included. Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to identify the presence of NPS. The ISTAART-MBI (International Society of Advance Alzheimer's Research and Treatment-Alzheimer's Association) diagnostic criteria was used to diagnose MBI. All the participants underwent a geriatric assessment using standardised screening. The objectives of this study was to determine the frequency of mild behavioural impairment (MBI), and its domains, in MCI or SCI and its association with comorbidities and geriatric syndromes. The mean age of the participants was 69.21, 71.77% (89) were male and 28.23% (35) were female. 41.13% (51) of these individuals were diagnosed with MBI. The MBI and non MBI group differed significantly in marital status, cognitive status and MCI subtype. The proportion of domains involved are as follows: decreased motivation 60.78%(31), emotional dysregulation 54.90% (28), impulse dyscontrol 68.63% (35), social inappropriateness 21.57%(11), abnormal perception 2 (3.93%). Presence of multi-morbidity, and diabetes, were statistically significant between the groups. This study presents the first clinic-based prevalence estimates of MBI from Asia. Findings indicate a relatively high prevalence of MBI in predementia clinical states, impulse dyscontrol was the most commonly involved MBI domain. Multimorbidity, diabetes, urinary incontinence were other determinants of MBI.

Background: Mild behavioral impairment (MBI) is considered to be a late life transitional state between normal aging and dementia that describes individuals who have persistent behavioral changes and/or psychiatric symptoms. Individuals with MBI are found to be at greater risk of dementia compared to those without these symptoms. Identifying how MBI might relate to different domains of cognition is of key importance, as it could be an early indicator of a future dementia diagnoses. Method: Secondary data analysis of a sample (n=512) of older adults from the Florida Alzheimer’s Disease Research Center who were either cognitively healthy or presenting with mild cognitive impairment (MCI). Some individuals presented with MBI, as defined by decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, or abnormal perception/thought content. Executive function, attention, short-term memory, and episodic memory, were compared using a battery of neuropsychological assessments. Results: Individuals with MCI performed worse on all tasks across all cognitive domains, where individuals with MBI performed worse on several tasks associated with executive function, attention, and episodic memory. Compared to individuals with only MCI, individuals with MCI and MBI performed significantly worse on tasks associated with executive function and episodic memory. Conclusion: The present study found evidence that individuals with MBI will perform worse on tasks of executive function, attention, and episodic memory. Further, those with MCI and MBI will perform significantly worse on executive function and episodic memory tasks. Future research should explore if these findings can help to predict specific dementia diagnoses.

MBI symptoms predict progression to Alzheimer's disease independent of neuropathology.

Over the past years, increasing attention has been paid to the frequency of neuropsychiatric symptoms (NPS) in dementia, also known as the behavioral and psychological symptoms of dementia. This study's main goal was to determine the prevalence of Mild Behavioral Impairment (MBI) and its subdomains in patients with Mild Cognitive Impairment (MCI) in Iran. Participants included 96 patients with MCI who attended the memory clinic between July and December 2020. Global cognitive function was evaluated using the Persian version of the Montreal Cognitive Assessment (MoCA). To assess MBI, the Persian version of the MBI checklist (MBI-C) was completed by the patient or a close caregiver. The mean age of patients was 71.4 ± 9.3years, and 56 patients (58.3%) were female. Regarding the cutoff point of 6.5, 48 patients (50%) had MBI. In both groups of MBI and non-MBI, 28 (58%) were female. There was no significant difference in MBI subdomains scores and total MBI scores between the two genders. In addition, we found no significant difference in total MBI in patients with different risk factors. There was no significant difference in MoCA score between MBI and non-MBI patients (24.1 ± 3.9 versus 23.7 ± 4.0) (p = 0.59). NPS are highly prevalent in MCI patients, with the most common ones being impulse dyscontrol, emotional dysregulation, and decreased motivation. Psychotic symptoms and social inappropriateness are rare. New-onset psychiatric symptoms and behavioral changes in older adults, even in a mild form (MBI), should increase the suspicion of subsequent cognitive impairment.

MILD BEHAVIORAL IMPAIRMENT AS A PREDICTOR OF COGNITIVE FUNCTIONING IN OLDER ADULTS

White matter hyperintensities and mild behavioral impairment: Findings from the MEMENTO cohort study.

Plasma phosphorylated tau at threonine 181 (p-tau181), a well-validated marker of Alzheimer disease (AD) pathologic change, could be a more efficient way to diagnose AD than invasive or expensive biomarkers requiring CSF or PET. In some individuals, neuropsychiatric symptoms (NPS) are the earliest manifestation of AD, observed in advance of clear cognitive decline. However, the few studies assessing AD biomarkers in association with NPS have often had imprecision in capturing behavioral symptoms that represent sequelae of neurodegenerative disease. Thus, the mild behavioral impairment (MBI) construct was developed, framing NPS in a way to improve the precision of risk estimates for disease. MBI core criteria stipulate that NPS emerge de novo in later life and persist for at least 6 months. Here, cross-sectionally and longitudinally, we investigated associations of MBI with p-tau181, neuropsychological test performance, and incident AD. Cognitively unimpaired and mild cognitive impairment (MCI) Alzheimer's Disease Neuroimaging Initiative participants were selected. MBI status was derived from the Neuropsychiatric Inventory (NPI) using a published algorithm. NPI total scores at baseline and year 1 visits were used to operationalize MBI (score >0 at both visits), NPS not meeting the MBI criteria (NPS-not-MBI, score >0 at only 1 visit), and no NPS (score = 0 at both visits). Linear regressions were fitted for cross-sectional analyses; multilevel linear mixed-effects and Cox proportional hazards models were implemented to examine the longitudinal associations of MBI with changes in p-tau181 and cognition and incident dementia. The sample included 571 participants (age 72.2 years, 46.8% female, 64.8% MCI). Cross-sectionally (β = 8.1%, 95% CI 1.4%-15.2%, p = 0.02), MBI was associated with higher plasma p-tau181 levels compared with no NPS; NPS-not-MBI was not. Longitudinally, MBI was associated with higher p-tau181 (β = 0.014%, 95% CI 0.003-0.026, p = 0.02), in addition to a decline in memory and executive function. Survival analyses demonstrated a 3.92-fold greater dementia incidence in MBI, with no significant differences between NPS-not-MBI and no NPS. These findings extend the evidence base that MBI is associated with elevated risk of cognitive decline and dementia and a sequela of emerging Alzheimer-related proteinopathies. MBI offers a substantial improvement over current approaches that explore behavior as a proxy marker for Alzheimer-related proteinopathies, with both clinical and AD trial enrichment implications.

Apathy and APOE in mild behavioral impairment, and risk for incident dementia.