Prevalence of mild behavioural impairment and its association with cognitive and functional impairment in normal cognition, mild cognitive impairment, and mild Alzheimer's dementia.

BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Proposed research criteria for prodromal behavioural variant frontotemporal dementia.

At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed 'mild behavioural and/or cognitive impairment in bvFTD' (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer's disease, and the false positive rate of diagnosis was 11-16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

A narrative review on mild behavioural impairment: an exploration into its scientific perspectives.

In clinical practice, the admission of patients with late-onset psychological and behavioural symptoms is frequent, regardless of the presence or absence of cognitive decline. These symptoms commonly occur in the prodromal stage of dementia and can precede the onset of dementia. While the concept of Mild Cognitive Impairment (MCI) -which is defined as a level of cognitive impairment insufficient to impact daily functioning- is well established, the notion of Mild Behavioural Impairment (MBI) is not yet widely recognized. However, studies have demonstrated that the presence of MBI in both cognitively normal patients and individuals with MCI is associated with an increased risk of dementia progression. Thus, MBI may serve as a neurobehavioral indicator of pre-dementia risk states. This narrative review aims to discuss the evolution of the term, the relevant clinical aspects, and potential biomarkers that may contribute to the clinical definition of MBI. The objective is to assist clinicians in recognizing the diagnosis and differentiating it from psychiatric syndromes, as well as identifying possible etiologies of neurodegeneration.

Plasma ß-Amyloid in Mild Behavioural Impairment - Neuropsychiatric Symptoms on the Alzheimer's Continuum.

INTRODUCTION: Simple markers are required to recognize older adults at higher risk for neurodegenerative disease. Mild behavioural impairment (MBI) and plasma ß-amyloid (Aß) have been independently implicated in the development of incident cognitive decline and dementia. Here we studied the associations between MBI and plasma Aß42/Aß40. METHODS: 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 Aß42/Aß40 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 Aß42/Aß40. RESULTS: Lower plasma Aß42/Aß40 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. CONCLUSION: In persons with normal cognition or mild cognitive impairment, MBI was associated with low plasma Aß42/Aß40. Incorporating MBI into case detection may help capture preclinical and prodromal Alzheimer's disease.

Neuropsychiatric symptoms and cerebrovascular risk in non-demented elders: cross-sectional study using the mild behavioural impairment checklist (MBI-C).

BACKGROUND: Neuropsychiatric symptoms (NPS) may represent early clinical manifestations of evolving brain diseases. Studies underpin the occurrence of NPS in the context of mild cognitive impairment (MCI) and prodromal Alzheimer's disease, where symptoms referred to as 'mild behavioural impairment' (MBI) have been shown to predict conversion to dementia and to hasten cognitive/functional decline. However, the association between NPS and cerebrovascular risk factors has been poorly investigated, despite the high prevalence of the latter among individuals with MCI. The aim of the present study was to investigate the association between MBI and cerebrovascular risk in a clinical sample of non-demented elders. METHODS: Sixty-five MCI and 15 cognitively unimpaired older adults were cross-sectionally assessed with the Mild Behavioural Impairment Checklist (MBI-C), using the cut-off score > 6.5 to define positive screening. Participants were submitted to the Hachinski Ischaemic Score (HIS) to account for cerebrovascular symptoms, vascular risk, and related comorbidities. Neuroimaging scans (magnetic resonance imaging and/or 18F-fluorodeoxyglucose-positron emission tomography) and apolipoprotein E genotype were obtained. RESULTS: Positive associations were found between total MBI-C scores and increasing number of comorbidities present (0-2 comorbidities), but not with three comorbidities. Two domains of the MBI-C-impulse dyscontrol and social inappropriateness-followed the same trend of the MBI-C total score, with higher scores with the increasing numbers of comorbidities. No significant associations were found between MBI symptoms and HIS or cerebrovascular burden in neuroimaging assessment. CONCLUSION: We found weak associations between MBI-C total score and the presence of comorbidities with cerebrovascular risk, but not with structural or functional neuroimaging abnormalities or HIS. This finding may represent that the presence of comorbidities adds limited risk to the occurrence of MBI in this sample of non-demented elders.

Prevalence of mild behavioural impairment domains: a meta-analysis.

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.

Prevalence of mild behavioural impairment: a systematic review and meta-analysis.

AIM: Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterized by emergent neuropsychiatric symptoms in later life. There has been no systematic review or meta-analysis on the prevalence of MBI. The main aim of the study is to calculate the pooled prevalence of MBI. METHODS: A search of the literature on MBI in mild cognitive impairment (MCI), cognitively normal (CN), and subjective cognitive impairment (SCI) and CN but at risk (CN-AR) subjects published between 1 January 2003 and 28 September 2020 was conducted. Meta-analysis using a random effects model was performed to determine the pooled estimate of the prevalence of MBI. Meta-regression was performed to identify factors contributing to the variance of prevalence rate. A systematic review was also performed to study the impact of MBI in cognitive outcomes and its correlation to the pathology and genetics of Alzheimer's disease. RESULTS: Eleven studies conducted among 15 689 subjects underwent meta-analysis, revealing the pooled prevalence of MBI to be 33.5% (95% confidence interval (CI): 22.6%-46.6%). Seven studies conducted among 1358 MCI subjects underwent meta-analysis, revealing the pooled prevalence to be 45.5% (95%CI: 36.1%-55.3%). Four studies conducted among 13 153 CN subjects underwent meta-analysis, revealing the pooled prevalence to be 17.0% (95%CI: 7.2%-34.9%). Five studies conducted among 1158 SCI or CN-AR subjects underwent meta-analysis, revealing the pooled prevalence to be 35.8% (95%CI: 21.4%-53.2%). A systematic review of 13 studies showed that MBI has a significant impact on cognitive deterioration and is associated with the pathology and genetics of Alzheimer's disease. CONCLUSIONS: In MCI, CN, and SCI and CN-AR subjects, MBI is common. Our finding is potentially useful in planning future clinical trials.

Neuropsychiatric Symptoms in Mild Cognitive Impairment: A Literature Review.

BACKGROUND: Neuropsychiatric symptoms (NPS) in dementia have received much attention due to their high prevalence and their significant implications. NPS in mild cognitive impairment (MCI), a clinical concept proposed as an intermediate state between normal aging and dementia, is now gradually gaining in interest. We aimed to conduct a selective review to examine the prevalence rate of NPS in MCI and associations of NPS symptoms with disease progression. SUMMARY: We searched the PubMed database for articles on NPS in MCI and included articles that fulfilled the inclusion criteria. NPS was present in 35-85% of MCI patients. The most common symptoms were depression, irritability, apathy, anxiety, agitation, and sleep problems. Although the associated risk for disease progression of some symptoms, such as apathy and anxiety, was more consistent across studies, evidence was conflicting for symptoms like depression and sleep problems. NPS tend to co-occur, and certain combinations of NPS had a mutual or cumulative effect on disease progression. Late-onset NPS, even in a mild form (mild behavioural impairment) were found to be associated with an increased risk of dementia, even in the absence of cognitive impairment. Key Messages: NPS are highly prevalent in MCI patients and associated with subsequent cognitive deterioration. Late-onset NPS should raise suspicions of neurodegeneration. Future studies with improvised methodology are required to understand the interrelations of NPS and the role they play in the prognosis for patients with MCI.

Discrete effect of each mild behavioural impairment category on dementia conversion or cognitive decline in patients with mild cognitive impairment.

BACKGROUND: Neuropsychiatric symptoms (NPS) have been recognized as risk factors for conversion to dementia in patients with mild cognitive impairment (MCI). Early detection of NPS may allow for possible interventions in such patients. The present study used mild behavioural impairment to explore the role of NPS in a wide range of patients, from those who are cognitively intact to those with dementia. METHODS: A total of 234 patients with mild cognitive impairment were followed up for up to 3 years in a Japanese cohort study. Longitudinal data from patients who developed dementia during the study and those who did not were statistically analyzed. RESULTS: Cox regression analysis revealed that only abnormal perception and thought was significant in terms of dementia conversion. Moreover, mixed-effects models indicated that baseline mild behavioural impairment symptoms did not affect cognitive trajectories such as changes in Mini-Mental State Examination or Alzheimer's Disease Assessment Scale-cognitive subscale scores. CONCLUSION: We conclude that only abnormal perception and thought content were risk factors for dementia and that NPS may not lead to deterioration of cognitive function in patients with mild cognitive impairment.

Effect of Hearing Ability and Mild Behavioural Impairment on MoCA and Memory Index Scores.

BACKGROUND: The life-course model of modifiable risk factors for dementia now recognizes managing hearing loss and addressing social isolation. OBJECTIVE: To investigate the contribution and inter-relationship of hearing ability and behaviour change on cognitive ability. METHODS: We present the preliminary findings from a prospective longitudinal study of 35 non-demented participants ages 60-93, recruited from community rehabilitation and acute-care programs of Geriatric Medicine, who underwent baseline hearing, behavioural, and cognitive testing. RESULTS: After controlling for age and hearing impairment, the left ear Dichotic Digit Test (DDT) score accounted uniquely for 20% of the variance in MoCA Memory Index (p = .016 with ß = .598). Mild Behavioural Impairment (MBI) was highly prevalent, with 80% of older adults reporting at least one MBI symptom. People with hearing impairment had greater global MBI burden than people with normal hearing, especially in the domains of apathy and impulse dyscontrol; however, greater severity of hearing impairment was not associated with a higher number of neuropsychiatric symptoms (NPS). CONCLUSIONS: Low left DDT contributed to lower memory index and greater MBI burden is associated with hearing impairment. Our findings demonstrate the value of early non-invasive hearing and behavioural assessments as part of dementia risk assessment in older adults.

Cortical markers of cognitive syndromes in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) can be associated with a spectrum of cognitive and behavioural symptoms, but the related patterns of focal cortical atrophy in non-demented ALS patients remain largely unknown. We enrolled 48 non-demented ALS patients and 26 healthy controls for a comprehensive neuropsychological assessment and a magnetic resonance exam. Behavioural and cognitive impairment was defined on the basis of a data-driven multi-domain approach in 21 ALS patients. Averaged cortical thickness of 74 bilateral brain regions was used as a measure of cortical atrophy. Cortical thinning in a fronto-parietal network, suggesting a disease-specific pattern of neurodegeneration, was present in all patients, independent of cognitive and behavioural status. Between-group and correlational analyses revealed that inferior frontal, temporal, cingular and insular thinning are markers for cognitive and behavioural deficits, with language impairment mainly related to left temporal pole and insular involvement. These specific correlates support the concept of a spectrum of deficits, with an overlap between the ALS cognitive phenotypes and the syndromes of frontotemporal dementia.