Impulse Dyscontrol Research Articles

Personality traits and measures of neuropsychiatric symptoms

Objectives Changes in personality and behavioral symptoms are a core clinical criterion for the diagnosis of dementia. This study examines the association between caregiver-rated personality traits and multiple measures of neuropsychiatric symptoms. Method Caregivers of individuals with dementia (N = 191) or cancer (N = 137) provided premorbid and concurrent personality trait ratings using the Big Five Inventory-2. Caregivers also completed the Mild Behavioral Impairment Checklist, Neuropsychiatric Inventory Questionnaire, and Revised Memory and Behavior Problems Checklist. Results In the combined sample, high concurrent neuroticism was associated with emotional dysregulation (r = 0.51), low agreeableness with impulse dyscontrol (r=-0.40), and low conscientiousness with decreased motivation (r=-0.42). Associations were similar across neuropsychiatric symptom scales, similar across cancer and dementia, but stronger with concurrent than premorbid personality ratings, and stronger for the individuals with mild than moderate-severe dementia. Conclusion Personality was associated with neuropsychiatric symptoms, including with the measure for mild behavioral impairment. Personality had stronger associations when concurrently assessed, indicating that personality traits co-develop with neuropsychiatric symptoms. The associations were similar across cancer and dementia, suggesting transdiagnostic processes not limited to dementia. Neuropsychiatric symptoms are partly an expression of personality; accounting for personality traits could help with diagnosis and disease monitoring, tailoring interventions, and fostering person-centered care.

Regional Burden of Enlarged Perivascular Spaces and Cognition and Neuropsychiatric Symptoms in Drug-Naive Patients With Parkinson Disease.

Although the potential role of enlarged perivascular spaces (EPVSs) in Parkinson disease (PD) is increasingly recognized, whether EPVSs located in different anatomical regions exert differential effects on clinical manifestation remains uncertain. We investigated the regional EPVS burden and its association with cognition and neuropsychiatric symptoms (NPSs) in newly diagnosed PD population. In this retrospective, cross-sectional study, EPVS in the temporal lobe (T-EPVS), centrum semiovale (CS-EPVS), and basal ganglia (BG-EPVS) were visually rated in drug-naive patients with PD who underwent magnetic resonance imaging, dopamine transporter (DAT) scans, neuropsychological assessments, and Neuropsychiatric Inventory Questionnaire at baseline. Cognitive performance, NPS burden, vascular risk factors, small vessel disease (SVD) imaging markers, and DAT availability were compared across groups dichotomized by their regional EPVS burden (cutoff for high-degree vs low-degree: >10 for T-EPVS/BG-EPVS and >20 for CS-EPVS). A total of 480 patients with PD (123 without cognitive impairment, 291 with mild cognitive impairment, and 66 with dementia) were included. The proportion of high-degree T-EPVS (p for trend <0.001) and BG-EPVS (p for trend = 0.001) exhibited an increasing trend across the cognitive spectrum, corresponding to worsening cognition. Compared with the low-degree group, the high-degree BG-EPVS group showed higher SVD burden (moderate-to-severe white matter hyperintensity [14.8% vs 40.5%, p < 0.001], lacune [10.3% vs 30.7%, p < 0.001], and cerebral microbleeds [8.1% vs 22.2%, p < 0.001]), greater atrophy in cortical gray matter (40.73% ± 1.09% vs 39.96% ± 1.20% of intracranial volume, p < 0.001), and lower cognitive performance (in language [-0.22 ± 1.18 vs -0.53 ± 1.29, p = 0.013], and visual memory domains [-0.24 ± 0.97 vs -0.61 ± 0.96, p = 0.009]). The high-degree T-EPVS group presented with greater NPS burden in decreased motivation (0.61 ± 1.78 vs 1.35 ± 2.36, p = 0.007), affective dysregulation (0.88 ± 2.13 vs 2.36 ± 3.53, p < 0.001), and impulse dyscontrol (0.43 ± 1.67 vs 1.74 ± 4.29, p < 0.001), compared with the low-degree T-EPVS group. Meanwhile, the burden of CS-EPVS did not reveal any differences in cognition or NPS. BG-EPVS and T-EPVS seem to exert differential effects on cognition and NPS in patients with PD. Investigating the EPVS profile in distinct anatomical regions may be useful in disentangling the heterogeneity within PD.

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

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. 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. 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. 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. 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.

Associations of Prior Head Injury With Mild Behavioral Impairment Domains.

This study investigated associations of prior head injury and number of prior head injuries with mild behavioral impairment (MBI) domains. The Atherosclerosis Risk in Communities (ARIC) Study. A total of 2534 community-dwelling older adults who took part in the ARIC Neurocognitive Study stage 2 examination were included. This 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. The primary outcome was the presence of impairment in MBI domains. Participants 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). Prior 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.

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

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.

Exploring the Genetic Landscape of Mild Behavioral Impairment as an Early Marker of Cognitive Decline: An Updated Review Focusing on Alzheimer's Disease.

The clinical features and pathophysiology of neuropsychiatric symptoms (NPSs) in dementia have been extensively studied. However, the genetic architecture and underlying neurobiological mechanisms of NPSs at preclinical stages of cognitive decline and Alzheimer's disease (AD) remain largely unknown. Mild behavioral impairment (MBI) represents an at-risk state for incident cognitive impairment and is defined by the emergence of persistent NPSs among non-demented individuals in later life. These NPSs include affective dysregulation, decreased motivation, impulse dyscontrol, abnormal perception and thought content, and social inappropriateness. Accumulating evidence has recently begun to shed more light on the genetic background of MBI, focusing on its potential association with genetic factors related to AD. The Apolipoprotein E (APOE) genotype and the MS4A locus have been associated with affective dysregulation, ZCWPW1 with social inappropriateness and psychosis, BIN1 and EPHA1 with psychosis, and NME8 with apathy. The association between MBI and polygenic risk scores (PRSs) in terms of AD dementia has been also explored. Potential implicated mechanisms include neuroinflammation, synaptic dysfunction, epigenetic modifications, oxidative stress responses, proteosomal impairment, and abnormal immune responses. In this review, we summarize and critically discuss the available evidence on the genetic background of MBI with an emphasis on AD, aiming to gain insights into the potential underlying neurobiological mechanisms, which till now remain largely unexplored. In addition, we propose future areas of research in this emerging field, with the aim to better understand the molecular pathophysiology of MBI and its genetic links with cognitive decline.

Mild behavioral impairment in early Alzheimer’s disease and its association with APOE and BDNF risk genetic polymorphisms

BackgroundMild behavioral impairment (MBI) has been commonly reported in early Alzheimer’s disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI severity. Within aMCI-AD, we further examined the association between APOE and BDNF risk genetic polymorphisms and MBI severity.MethodsWe included 62 aMCI-AD participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging. MBI was diagnosed with the Mild Behavioral Impairment Checklist (MBI-C), and the diagnosis was based on the MBI-C total score ≥ 7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the associations.ResultsMBI was present in 48.4% of the aMCI-AD individuals. Compared to the CN, aMCI-AD was associated with more affective, apathy, and impulse dyscontrol but not social inappropriateness or psychotic symptoms. Furthermore, aMCI-AD was related to more depressive but not anxiety symptoms on self-report measures. Within the aMCI-AD, there were no associations between APOE e4 and BDNF Met and MBI-C severity. However, a positive association between Met carriership and self-reported anxiety appeared.ConclusionsMBI is frequent in aMCI-AD and related to more severe affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF polymorphisms were not associated with MBI severity separately; however, their combined effect warrants further investigation.

Clinical Manifestations.

Impulse dyscontrol, i.e., excessive motor activity and/or physical and verbal aggression is common in dementia. However, impulse dyscontrol can also emerge in advance of dementia, but is often normalized due to age, or framed as a psychiatric condition. Thus, the association between these symptoms and incident dementia is unclear. Mild behavioral impairment (MBI) leverages risk associated with later-life emergent and persistent neuropsychiatric symptoms (NPS) to identify a high-risk group for incident dementia. Impulse dyscontrol is one of five MBI domains. Here, in dementia-free participants, we assessed risk of progression to dementia in MBI-impulse dyscontrol and conventionally-measured impulse dyscontrol symptoms (Conv-ID). Dementia-free National Alzheimer Coordinating Centre participants were included. Neuropsychiatric Inventory Questionnaire irritability, agitation, and aberrant motor behavior items were used to identify impulse dyscontrol. MBI-impulse dyscontrol was operationalized by symptom presence at more than two-thirds of pre-dementia study visits (symptom persistence criterion) in those with no history of psychiatric disorders (symptom emergence criterion). Conv-ID required symptoms only at baseline without consideration of past psychiatric history. Kaplan-Meier survival curves and Cox proportional hazards models, adjusted for age, sex, education, race, and APOE-e4 status, were generated to compare survival probability and dementia incidence rates of MBI-impulse dyscontrol and Conv-ID to No-NPS. The sample comprised 1,884 MBI-impulse dyscontrol (age = 74.5±9.7; 40.9% female), 3,676 Conv-ID (age = 71.0±9.4; 47.0% female), and 6,362 No-NPS participants (age = 71.0±10.3; 64.7% female) (Table 1). MBI-impulse dyscontrol had lower dementia-free survival (p<0.0001) and 2.23-fold greater dementia incidence compared to No-NPS (CI:1.99-2.50, p<0.001, Figure 1(A)); Conv-ID had lower dementia-free survival (p<0.0001) and 1.39-fold greater dementia incidence compared to No-NPS (CI:1.25-1.54, p<0.001, Figure 1(B)). Compared with a conventional approach to assess agitated and impulsive behaviors, MBI-impulse dyscontrol was associated with greater dementia incidence. Applying the MBI criteria of later-life emergence and persistence of symptoms provides a more specific approach to identify those at risk for incident dementia, who might otherwise be dismissed due to normalization of these behaviors in older persons or labelled with a psychiatric condition. This approach may allow for earlier implementation of preventative measures, pharmacological and non-pharmacological, improving outcomes and quality of life for patients and their caregivers.

Comparison between self‐ and informant‐rated versions of the Mild behavioral impairment checklist in patients with mild cognitive impairment

AbstractBackgroundMild behavioral impairment (MBI) describes de novo emergent and persistent neuropsychiatric symptoms in older individuals. MBI is common in individuals with mild cognitive impairment (MCI), but self‐endorsed symptoms may not align with reports from informants. In this study, we explore the consistency between self‐ and informant‐rated versions of the Mild behavioral impairment checklist (MBI‐C), which is used to assess MBI.MethodWe included 68 individuals with MCI (MMSE 26.59±2.55) who underwent neurological, extensive neuropsychological examination and brain MRI within the Czech Brain Aging Study and had no history of prior psychiatric disorder. Both participants and their close informants completed The Czech version of the MBI‐C (MBI‐C self and MBI‐C informant, respectively). The consistency and differences between the MBI‐C self and informant total and domain scores (i.e. motivation, affect, impulse dyscontrol, social inappropriateness and psychotic symptoms), and the presence of MBI based on a cut‐off of ≥7, were examined using Wilcoxon signed‐rank test, the binomial test and Spearman´s rank correlation. Further, we explored the association between the informant‐self score difference with the MMSE as a measure of global cognition.ResultThere was no difference between MBI‐C self and informant total score (both median ratings were 5.0). Among the domain scores, we observed a difference between self and informant ratings in the impulse dyscontrol (Z = ‐2.97, p = 0.003), but not in any other score. Disagreements on the presence of MBI were observed in 19 participants (28%), but both patients and informants were equally likely to disagree on the MBI presence vs. absence. We observed weak to modest correlations between MBI‐C self and informant total and domain scores (rS = 0.34‐0.53, ps&lt;0.01). The informant‐self score difference in MBI‐C impulse dyscontrol was negatively associated with the MMSE (rS = ‐0.39, p = 0.001).ConclusionPatients with MCI and their informants were not consistent regarding the presence of MBI, but among those who disagreed, neither informants nor patients were more likely to report MBI. The informants reported more severe impulse dyscontrol symptoms compared to the patients with MCI themselves and this difference was negatively associated with lower MMSE. The observed inconsistencies provide implications for clinical and research settings.

Clinical Manifestations.

The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI-C, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI-C, NPI-Q, and FBI, and cutoff points were determined using the Youden index. The MBI-C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI-C score was positively correlated with the NPI-Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI-C cutoff point was 5/6 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI-Q and FBI. The MBI-C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.

Temporal associations between treated and untreated hearing loss and mild behavioral impairment in older adults without dementia

AbstractBackgroundHearing loss and mild behavioral impairment (MBI) are non‐cognitive markers of dementia that are cross‐sectionally linked to one another. Longitudinal approaches are necessary to further understand mechanisms underlying their association, which may inform interventions for hearing loss and MBI. This study investigated the relationship between hearing loss, with or without hearing aids (HAs), and MBI in dementia‐free older adults both cross‐sectionally and longitudinally.MethodData were analyzed from dementia‐free National Alzheimer’s Coordinating Center participants, aged ≥50, collected between 2005‐2022. Three self‐report questions were used to generate a three‐level categorical hearing status variable: No‐HL, Untreated‐HL (not wearing hearing aids), and Treated‐HL (regularly wearing hearing aids). MBI status was derived from the informant‐rated Neuropsychiatric Inventory Questionnaire using a published algorithm. At baseline (n = 7992), age‐, sex‐, education‐, and cognitive status‐adjusted logistic regression was used to examine the association between hearing status and presence of global and domain‐specific MBI. Cox proportional hazards models examined the effect of: 1) hearing status as exposure on rate of incident MBI (n = 6639); and 2) MBI status as exposure on rate of incident hearing loss (n = 7343).ResultCross‐sectionally, participants with Untreated‐HL (not wearing hearing aids) were more likely to exhibit global MBI (OR = 1.58) and individual MBI domains of social inappropriateness (OR = 2.08), affective dysregulation (OR = 1.64), and impulse dyscontrol (OR = 1.68), compared to those with No‐HL (Figure 1). Treated‐HL (regularly wearing hearing aids) did not differ from No‐HL for presence of global‐ or domain‐specific MBI. Longitudinally, older adults with Treated‐HL developed MBI at higher rates than No‐HL (HR = 1.42), and older adults with MBI at baseline developed Treated‐HL at higher rates than those without MBI (HR = 1.34) [Table 1].ConclusionOur cross‐sectional results indicate that HA use in dementia‐free hearing‐impaired older adults is associated with lower likelihood of having MBI. However, hearing loss requiring hearing aids was associated with incident MBI and vice versa. This bidirectional relationship may indicate a positive feedback loop between hearing loss and MBI, with Treated‐HL and MBI reflecting greater hearing loss severity and disease burden, increasing the rate of development of the complementary marker and of dementia.

P154: Mild Behavioral Impairment (MBI) in a sample of general population aged &gt; 55: associations with degree of cognitive impairment.

Objective:The present study aims to determine the prevalence estimates of MBI and specific MBI domains in a large sample of the general population, by degree of cognitive impairment (CI).Method:A representative community sample of individuals aged 55+ (n=4803) (ZARADEMP Study) was studied. MBI, and specific MBI domains, were assessed according to ISTAART-AA MBI criteria, using the Geriatric Mental State (GMS). In accordance with these criteria, clinically significant anxiety, depression, and dementia were excluded. For the standardized degree of CI Perneczky et al. ́s criteria were applied: normal (MMSE 30), questionable (MMSE 26-29), mild CI (MMSE 21-25), moderate-severe CI (MMSE &lt;21).Results:The prevalence of MBI, and specifically the domain Decrease Motivation (DM), increased progressively and significantly by degree of CI, the differences being significant between all cognitive groups. After control by age and education, DM was 2- and 4.5-times more frequent in subjects with mild CI (10.6%) and moderate-severe CI (18.3%), respectively, than in cognitive normal (5.8%). Affective Dysregulation (AD) was 1.7-times more frequent in mild CI (26.4%) (vs 20.4% in normal). Impulsive Dyscontrol (ID) was 2- and 7.9-times more frequent in mild CI (8%) and moderate-severe CI (23.5%) than in cognitive normal (4.7%). And Abnormal Perception and Thoughts (APT) was 6-times more frequent in moderate-severe CI (10%) (vs 1.4% in cognitive normal).Conclusion:Our results confirm an increase of MBI prevalence across the spectrum of CI. However, each specific domain of MBI shows a different pattern of association with CI. Our results support the relevance of studying MBI domains independently.

Risk of Mild Behavioral Impairment: the role of gender and APOE allele carrier status

AbstractBackgroundGender differences in dementia and dementia‐related neuropsychiatric symptoms are well described. Similarly, the Apolipoprotein E (APOE) ε4 allele is a well‐known predictor of Alzheimer’s disease. However, their impact on the clinical manifestation of Mild Behavioral Impairment (MBI) remains unclear. Using data from the Australian population‐based PATH Through Life Study we explored the associations between gender and APOE ε4 carrier status with MBI. We hypothesized that MBI likelihood would be greater in males and ε4 carriers.Method1316 dementia‐free participants (48% female; aged 72‐79) were included. Gender was self‐reported (female/male). Participants were classified as APOE ε4+ if they carried at least one ε4 allele (APOE ε4/ε4, ε2/ε4, ε3/ε4). MBI was approximated using a previously published transformation algorithm, which utilizes items from the Neuropsychiatric Inventory assessed at a single study visit. Binomial logistic regression was used to examine the role of gender and APOE ε4 carrier status, and their interaction, on predicting MBI status, while controlling for self‐reported years of education.ResultOf the 1316 participants, 339 (25.8%) were APOE ε4+ and 445 (34%) had MBI symptoms. A higher proportion of APOE ε4+ carriers (χ2 (1) = 5.99, p = .014) and men (χ2 (1) = 4.59, p = .032) were in the MBI group compared to the non‐MBI group. Binomial logistic regression showed APOE ε4 carrier status (OR = 1.58, 95% CI: 1.063‐2.344) and male gender (OR = 1.45, 95% CI: 1.093‐1.925) were associated with a greater likelihood of MBI. Male gender was also associated with a 2‐fold greater likelihood of having symptoms of the Decreased Motivation (OR = 2.08, 95% CI: 1.13‐3.86) and Impulse Dyscontrol (OR = 2.16, 95% CI: 1.54‐3.03) domains. No interaction effects were found between gender and APOE ε4 carrier status for MBI or any of its domains.ConclusionThe current study found that in dementia‐free older adults both male gender and APOE ε4+ status increased the risk of having MBI. However, no cumulative/interaction effect between gender and APOE ε4 carrier status was found, suggesting that being both male and APOE ε4+ does not further increase the risk of MBI. These results provide novel and valuable insight into the connection between gender, APOE ε4 carrier status and MBI.

Mild behavioral impairment in prodromal Alzheimer´s disease and its association with APOE and BDNF risk genetic polymorphisms

Objective:We aimed to examine the profile and severity of mild behavioral impairment (MBI) in a sample of β-amyloid positive individuals with amnestic mild cognitive impairment (aMCI)compared to cognitively normal older adults (CN). Within aMCI, we further examined the potential influence of APOE and BDN Frisk genetic polymorphisms on MBI severity.Methods:We included 64 β-amyloid positive aMCI participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging.MBI was diagnosed with the Mild behavioral impairment checklist (MBI-C) developed for MBI case detection, and the diagnosis was based on the MBI-C total score ≥7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the between-group differences.Results:MBI symptoms (MBI-C total score ≥1) were present in 28% CN and 83% aMCI. Almost half (48.4%) of the aMCI individuals met the criteria for the MBI syndrome. Compared to the CN, the aMCI group displayed more affective, apathy, and impulse dyscontrol symptoms (p&lt;0.001) but not social inappropriateness or psychotic symptoms. Furthermore, aMCI participants reported more depressive (p&lt;0.01) but similar anxiety symptoms to CN on self-report measures. Within the aMCI group, APOE e4 and BDNF Met carriers did not differ from non-carriers in the severity of NPS in either instrument. However, the results suggested that an interaction between these polymorphisms influenced self-reported anxiety (p=0.034), with Met carriers/e4 non-carriers reporting the highest anxiety levels.Conclusion:MBI is frequent in prodromal Alzheimer´s disease and characterized by affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF risk genetic polymorphisms did not influence the NPS severity when considered separately; however, their interaction might influence anxiety, which warrants further investigation.The research has received funding from the EEA/ Norway Grants 2014-2021 and the Technology Agency of the Czech Republic – project number TO01000215, Ministry of Health of the Czech Republic, grant no. 19-04-00560, National Institute for Neurological Research (Programme EXCELES, ID Project No. LX22NPO5107) - funded by the European Union – Next Generation EU and GAČR 22-33968S.

Temporal associations between treated and untreated hearing loss and mild behavioral impairment in older adults without dementia.

Hearing 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. Data 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). Cross-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). Our 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. Hearing 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.

Application of the mild behavioral impairment checklist in Chinese patients with the behavioral variant of frontotemporal dementia.

The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI-C, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI-C, NPI-Q, and FBI, and cutoff points were determined using the Youden index. The MBI-C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI-C score was positively correlated with the NPI-Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI-C cutoff point was 5.5 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI-Q and FBI. The MBI-C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.

Contribution of amyloid and putative Lewy body pathologies in neuropsychiatric symptoms.

Neuropsychiatric symptom could be useful for detecting patients with prodromal dementia. Similarities and differences in the NPSs between preclinical/prodromal Alzheimer's disease (AD) and prodromal Parkinson's disease dementia (PDD)/Dementia with Lewy bodies (DLB) may exist. This study aimed to compare the NPSs between preclinical/prodromal AD and prodromal PDD/DLB. One hundred and three participants without dementia aged ≥50years were included in this study. The mild behavioral impairment (MBI) total score and the MBI scores for each domain were calculated using the neuropsychiatric inventory questionnaire score. Participants were divided into five groups based on the clinical diagnosis by neurologists or psychiatrists in each institution based on the results of the amyloid positron emission tomography and dopamine transporter single photon emission computed tomography (DAT-SPECT): Group 1: amyloid-positive and abnormal DAT-SPECT, Group 2: amyloid-negative and abnormal DAT-SPECT, Group 3: amyloid-positive and normal DAT-SPECT, Group 4: mild cognitive impairment unlikely due to AD with normal DAT-SPECT, and Group 5: cognitively normal with amyloid-negative and normal DAT-SPECT. The MBI abnormal perception or thought content scores were significantly higher in Group 1 than Group 5 (Bonferroni-corrected p=0.012). The MBI total score (Bonferroni-corrected p=0.011) and MBI impulse dyscontrol score (Bonferroni-corrected p=0.033) in Group 4 were significantly higher than those in Group 5. The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms.

Sex differences in the prevalence of mild behavioral impairment: A systematic review and meta‐analysis

AbstractBackgroundMild behavioral impairment (MBI) is an early indicator of dementia risk characterized by the later life onset of persistent changes in behaviour or personality. An under‐investigated feature of MBI is the difference in symptoms and risk based on sex. This systematic review and meta‐analysis investigates the differences in the prevalence of MBI domains based on sex.MethodEMBASE, MEDLINE, PsycINFO and the grey literature were systematically searched for articles mentioning MBI. Participants with dementia were excluded. Abstracts and full‐text articles retrieved from the search were screened by two independent reviewers and included if sex‐specific prevalence data were reported. A standardized data extraction sheet was used for included articles, with data items for demographics, cognitive diagnosis, prevalence of females within each MBI domain, stratified by sex. There was insufficient evidence to look at gender. A random‐effects meta‐analysis was performed to combine the extracted data to identify pooled prevalence.ResultA total of 5476 articles were retrieved from the initial search, and 3435 papers remained after deduplication. After full‐text screening, 35 papers were selected for data extraction. In normal cognition, four out of five MBI domains were more prevalent in males (decreased motivation, impulse dyscontrol, social inappropriateness and abnormal perception or thought content). In mild cognitive impairment (MCI), three out of five domains were more prevalent in males (decreased motivation, impulse dyscontrol, and abnormal perception or thought content). However, in the mixed cognitive category, four out of five domains were more prevalent in females (decreased motivation, emotional dysregulation, impulse dyscontrol and social inappropriateness (Table 1).ConclusionIn this group of dementia‐free older adults, sex differences in prevalence of MBI domains varied by baseline cognitive status. Although the differences are not large, these findings raise interesting questions about sex‐specific trajectories of neuropsychiatric symptoms across the cognitive spectrum. This study highlights the need to explore differences in MBI by factors such as sex and gender.

Mild behavioral impairment linked to phenoconversion to Alzheimer’s disease and cortical thinning in mild cognitive impairment

AbstractBackgroundMild Behavioral Impairment (MBI) is a neurobehavioral syndrome characterized by later life emergence of sustained neuropsychiatric symptoms, as an at‐risk state for dementia (Ismail Z, Alzheimers Dement, 2016). However, the associations between MBI and a risk of phenocoversion to dementia and its neuroanatomical correlates in MCI are still unclear.MethodA total 1326 older adults with MCI was followed for a mean of 3.0 ± 2.0 years. MBI was approximated using a transformation algorithm for the neuropsychiatric inventory at baseline. Two‐step cluster analysis was used to explore classes of 5 MBI domains (decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, abnormal perception/thought content). A Cox regression analysis was applied to investigate the association between the clusters and phenoconversion to AD. A subset of participants (n = 225) underwent 3D T1‐weighted MRI scans and cortical thickness was compared among the clusters of MBI domains.ResultThe cluster analysis identified 3 groups of participants: (1) people without MBI (47.8%, asymptomatic); (2) people with only affective dysregulation (29.3%, affective dysregulation); (3) people with relatively high probability of affective dysregulation, followed by impulse dyscontrol and affective dysregulation (22.9%, multiple domains). Compared to the asymptomatic, multiple domains was associated with a higher risk of phenoconversion to AD (hazard ratio = 2.589 [1.981 – 3.385], p = &lt; 0.001), but affective dysregulation did not predict phenoconversion (1.204 [0.896 – 1.620], p = 0.219) (Fig 1). MCI individuals with symptoms in multiple domains revealed thinning in the bilateral superior and inferior parietal, superior temporal, and prefrontal cortex, and the right precuneus compared to those with only affective dysregulation (Fig 2). We did not find differences in cortical thickness between phenocoverter and non‐phenoconverter, and interaction of clusters of MBI domains and phenoconversion.ConclusionThe multiple co‐occuring MBI domains in individuals with MCI are associated with a higher risk of phenoconversion to AD. Moreover, MCI individuals with symptoms in multiple domains revealed cortical thinning in the superior parietal and precuneus, which have suggested as AD signatures (Dickerson BC, Cereb Cortex, 2009). These results suggest that evaluation of MBI and neuroimaging characteristics could be useful for risk stratification in MCI individuals.

The Structure of Compulsive Sexual Behavior: A Network Analysis Study

Compulsive sexual behavior is a phenomenon characterized by a persistent failure to control intense, repetitive sexual impulses or urges, resulting in repetitive sexual behavior that causes marked distress or impairment in personal, familial, social, educational, or occupational areas of functioning. Despite its major impact on mental health and quality of life, little is known about its internal structure and whether this phenomenon differs across genders, age groups, and risk status. By considering a large online sample (n = 3186; 68.3% males), ranging from 14 to 64 years old, compulsive sexual behavior was explored by means of network analysis. State-of-the-art analytical techniques were adopted to investigate the pattern of association among the different elements of compulsive sexual behavior, identify possible communities of nodes, pinpoint the most central nodes, and detect differences between males and females, among different age groups, as well as between individuals at low and high risk of developing a full-blown disorder. The analyses revealed that the network was characterized by three communities, namely Consequence, Preoccupation, and Perceived Dyscontrol, and that the most central node was related to (perceived) impulse dyscontrol. No substantial differences were found between males and females and across age. Failing to meet one’s own commitments and responsibilities was more central in individuals at high risk of developing a full-blown disorder than in those at low risk.