Studies in cognitively normal individuals on associations between psychiatric symptomatology and incident dementia have not reliably differentiated psychiatric syndromes from neuropsychiatric symptoms (NPS) that represent neurodegeneration. Conventional modelling often overlooks symptom natural history. Mild behavioural impairment (MBI) is a syndrome that leverages later-life emergent and persistent NPS to identify a high-risk group for incident dementia.

We aimed to explore associations of MBI, and conventionally-measured NPS (NPS-not-MBI), with incident dementia in cognitively normal individuals and the cognitively normal subset with subjective cognitive decline (SCD).

Using National Alzheimer's Coordinating Center data, MBI was operationalised by the absence of past psychiatric disorders (symptom emergence) and the presence of symptoms at >2/3 of pre-dementia visits (symptom persistence). Kaplan–Meier survival curves and Cox proportional hazards regressions modelled dementia incidence across NPS groups and MBI domains, adjusted for age, gender, education, race, APOE-ε4, and cognitive status.

The sample comprised 1408 MBI (age 75.2 ± 9.5; 54.3% female), 5625 NPS-not-MBI (age 71.6 ± 8.8; 65.5% female) and 5078 No-NPS (age 71.2 ± 8.9; 67.6% female) participants. Compared with No-NPS, MBI participants had lower dementia-free survival (P < 0.0001) and 2.76-fold greater adjusted dementia incidence rate (95% CI: 2.27–3.35, P < 0.001); incidence rate in NPS-not-MBI did not differ from No-NPS (hazard ratio 0.97, 95% CI: 0.82–1.14, P = 0.687). Of those with MBI who progressed to dementia, 76.0% developed Alzheimer's disease. Similarly, in the SCD subsample (n = 3485), persons with MBI had 1.99-fold greater dementia incidence versus No-NPS (95% CI: 1.46–2.71, P < 0.001) while NPS-not-MBI did not differ from No-NPS (hazard ratio 0.92, 95% CI: 0.70–1.19, P = 0.511).

Incorporating natural history into assessment of psychiatric symptoms in accordance with MBI criteria enhances dementia prognostication and modelling.

We explored the influence of study partner (SP) characteristics on SP-reported neuropsychiatric symptoms (NPS) presence across the neurocognitive spectrum and on the prognostic utility of mild behavioral impairment (MBI).

We performed cross-sectional (n = 26,748) and longitudinal (n = 12,794) analyses using participant-SP dyad data from the National Alzheimer’s Coordinating Center. Participants were cognitively normal (CN; n = 11,951) or had mild cognitive impairment (MCI; n = 5686) or dementia (n = 9111).

SPs rated NPS using the Neuropsychiatric Inventory Questionnaire. We used multivariable logistic regression to model the association between SP characteristics (age, sex, and relationship to participant [spouse, child, and other]) and NPS status (outcome). Cox regressions assessed SP characteristics as moderators of MBI associations with incident dementia or as predictors of incident dementia in MBI + participants only.

Among CN persons, younger, female, and spouse SPs reported NPS more frequently. In MCI, younger SPs and those who were spouses or children of participants reported higher NPS odds. For dementia participants, NPS odds were higher in female and spouse SPs. MBI associations with incident dementia were slightly weaker when SPs were older but did not depend on SP sex or relationship to participant. Among MBI + participants with spouse or child SPs, hazard for dementia was higher when compared to MBI + participants with other SPs.

SP age, sex, and relationship to participant influence NPS reporting across the neurocognitive spectrum, with potential implications for MBI prognosis. Considering SP characteristics may enhance the accuracy of NPS assessments, which may facilitate therapy planning and prognosis.

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.

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.

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<0.001) but not social inappropriateness or psychotic symptoms. Furthermore, aMCI participants reported more depressive (p<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.

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.

The assessment of MBI involves two important issues: 1) to know the underlying structure of the Mild Behavioral Impairment Checklist (MBI-C) a questionnaire designed to evaluates Neuropsychiatric Symptoms (NPS) in pre-dementia states; and 2) to consider self and proxy (i.e., study partner) symptom ratings that may not capture comparable samples. Our objective is to give some answer to these questions: first, to analyze the underlying structure of the MBI-C at baseline and follow-up using Multidimensional Scaling (MDS) and two, to determine how self and proxy ratings and the choice of rating type impact in the results of the MBI-C.

To analyze MBI-C structure, 200 Subjective Cognitive Decline and Mild Cognitive Impairment patients from the CompAS longitudinal study completed baseline and follow-up assessments. Two-step bidimensional weighted dichotomous MDS were performed. All items were included in the first step. Items closely associated with each dimension (1 SD above or below the mean) were selected in a second step to obtain the final models solution.

We will also present a review of the literature on the importance of self and proxy MBI-C ratings. We will also present new empirical evidence based on data from over 10,000 cognitively normal.

Results from baseline and follow-up showed two dimensions: Dimension I (right-left) differentiate high and low emotional activation and Dimension II (top-down) high and low behavioral activation. The combination of both generates 4 quadrants: resistance, restlessness, flattening and desolation. The final models were built considering the most relevant items, with little differences between baseline and follow-up. The good fit of the models, type of two-dimensional solution and group weights were similar in baseline and follow-up.

Regarding our second objective, the results suggest that self and proxy ratings may not capture comparable samples and that the choice of rating type can indeed impact the conclusions drawn from analysis.

The 4 quadrants identified could be the most useful NPS to determine risk factors for predementia patients. Also, the findings suggest that the way of applying the MBI-C has relevant implications.

The International Psychogeriatric Association (IPA) published a provisional consensus definition of agitation in cognitive disorders in 2015. As proposed by the original work group, we summarize the use and validation of criteria in order to remove “provisional” from the definition.

This report summarizes information from the academic literature, research resources, clinical guidelines, expert surveys, and patient and family advocates on the experience of use of the IPA definition. The information was reviewed by a working group of topic experts to create a finalized definition.

We present a final definition which closely resembles the provisional definition with modifications to address special circumstances. We also summarize the development of tools for diagnosis and assessment of agitation and propose strategies for dissemination and integration into precision diagnosis and agitation interventions.

The IPA definition of agitation captures a common and important entity that is recognized by many stakeholders. Dissemination of the definition will permit broader detection and can advance research and best practices for care of patients with agitation.

To develop an agitation reduction and prevention algorithm is intended to guide implementation of the definition of agitation developed by the International Psychogeriatric Association (IPA)

Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion

IPA Agitation Workgroup

IPA panel of international experts on agitation

Integration of available information into a comprehensive algorithm

None

The IPA Agitation Work Group recommends the Investigate, Plan, and Act (IPA) approach to agitation reduction and prevention. A thorough investigation of the behavior is followed by planning and acting with an emphasis on shared decision-making; the success of the plan is evaluated and adjusted as needed. The process is repeated until agitation is reduced to an acceptable level and prevention of recurrence is optimized. Psychosocial interventions are part of every plan and are continued throughout the process. Pharmacologic interventions are organized into panels of choices for nocturnal/circadian agitation; mild-moderate agitation or agitation with prominent mood features; moderate-severe agitation; and severe agitation with threatened harm to the patient or others. Therapeutic alternatives are presented for each panel. The occurrence of agitation in a variety of venues—home, nursing home, emergency department, hospice—and adjustments to the therapeutic approach are presented.

The IPA definition of agitation is operationalized into an agitation management algorithm that emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches to reflect the clinical situation, and shared decision-making.

Older adults experience symptoms of depression, leading to suffering and increased morbidity and mortality. Although we have effective depression therapies, physical distancing and other public health measures have severely limited access to in-person interventions.

To describe the efficacy of virtual interventions for reducing symptoms of depression in community-dwelling older adults.

Systematic review.

We searched MEDLINE, EMBASE, Cochrane Libraries, PsycINFO, and gray literature from inception to July 5, 2021.

We included randomized trials (RCTs) comparing the efficacy of virtual interventions to any other virtual intervention or usual care in community-dwelling adults ≥60 years old experiencing symptoms of depression or depression as an outcome.

The primary outcome was change in symptoms of depression measured by any depression scale.

We screened 12,290 abstracts and 830 full text papers. We included 15 RCTs (3100 participants). Five RCTs examined persons with depression symptoms at baseline and ten examined depression as an outcome only. Included studies demonstrated feasibility of interventions such as internet or telephone cognitive behavioral therapy with some papers showing statistically significant improvement in depressive symptoms.

There is a paucity of studies examining virtual interventions in older adults with depression. Given difficulty in accessing in-person therapies in a pandemic and poor access for people living in rural and remote regions, there is an urgent need to explore efficacy, effectiveness, and implementation of virtual therapies.

Depression is common in persons experiencing mild cognitive impairment (MCI), with 32% (95% Cl 27, 37) overall experiencing depression. Persons with MCI who have depression have more cognitive changes compared to those without depression. To understand how we can detect depressive symptoms in persons with MCI, we undertook a systematic review to identify tools that were validated compared with a reference standard.

We searched MEDLINE, EMBASE, PsycINFO, and Cochrane from inception to April 25, 2021, and conducted a gray literature search. Title/abstract and full-text screening were completed in duplicate. Demographic information, reference standards, prevalence, and diagnostic accuracy measures were then extracted from included articles (PROSPERO CRD: CRD42016052120).

Across databases, 8,748 abstracts were generated after removing duplicates. Six hundred and sixty-five records underwent full-text screening, with six articles included for data extraction. Nine tools were identified compared to a reference standard, with multiple demonstrating a sensitivity of 100% (Brief Assessment Schedule Depression Cards, Beck Depression Inventory-II, Cornell Scale for Depression in Dementia, Zung Self-Rated Depression Scale, and the Neuropsychiatric Inventory). The second highest sensitivity reported was 89% (Patient Health Questionnaire-9). Too few studies were available for a meta-analysis.

Multiple depression detection tools have been examined amongst MCI outpatients, with several showing high sensitivity. However, this evidence is only present in single studies, with little demonstration of how differing MCI types affect accuracy. More research is needed to confirm the accuracy of these tools amongst persons with MCI. At this time, several tools could be suitable for use in cognitive clinics.

In this large population study, we set out to examine the profile of mild behavioral impairment (MBI) by using the Mild Behavioral Impairment Checklist (MBI-C) and to explore its factor structure when employed as a self-reported and informant-rated tool.

This was a population-based cohort study.

Participants were recruited from the Platform for Research Online to Investigate Genetics and Cognition in Aging study (https://www.protect-exeter.org.uk).

A total of 5,742 participant-informant dyads participated in the study.

Both participants and informants completed the MBI-C. The factor structure of the MBI-C was evaluated by exploratory factor analysis.

The most common MBI-C items, as rated by self-reported and informants, related to affective dysregulation (mood/anxiety symptoms), being present in 34% and 38% of the sample, respectively. The least common items were those relating to abnormal thoughts and perception (psychotic symptoms) (present in 3% and 6% of the sample, respectively). Only weak correlations were observed between self-reported and informant-reported MBI-C responses. Exploratory factor analysis for both sets of respondent answers indicated that a five-factor solution for the MBI-C was appropriate, reflecting the hypothesized structure of the MBI-C.

This is the largest and most detailed report on the frequency of MBI symptoms in a nondementia sample. The full spectrum of MBI symptoms was present in our sample, whether rated by self-reported or informant report. However, we show that the MBI-C performs differently in self-reported versus informant-reported situations, which may have important implications for the use of the questionnaire in clinic and research.

To estimate the prevalence of Mild Behavioral Impairment (MBI) in people with Subjective Cognitive Decline (SCD), and validate the Mild Behavioral Impairment Checklist (MBI-C) with respect to score distribution, sensitivity, specificity, and utility for MBI diagnosis, as well as correlation with other neuropsychological tests.

Correlational study with a convenience sampling. Descriptive, logistic regression, ROC curve, and bivariate correlations analyses were performed.

Primary care health centers.

127 patients with SCD.

An extensive evaluation, including Questionnaire for Subjective Memory Complaints, Mini-Mental State Examination, Cambridge Cognitive Assessment-Revised, Neuropsychiatric Inventory-Questionnaire (NPI-Q), the Geriatric Depression Scale-15 items (GDS-15), the Lawton and Brody Index and the MBI-C, which was administered by phone to participants’ informants.

MBI prevalence was 5.8% in those with SCD. The total MBI-C scoring was low and differentiated people with MBI at a cut-off point of 8.5 (optimizing sensitivity and specificity). MBI-C total scoring correlated positively with NPI-Q, Questionnaire for Subjective Cognitive Complaints (QSCC) from the informant and GDS-15.

The phone administration of the MBI-C is useful for detecting MBI in people with SCD. The prevalence of MBI in SCD was low. The MBI-C detected subtle Neuropsychiatric symptoms (NPS) that were correlated with scores on the NPI-Q, depressive symptomatology (GDS-15), and memory performance perceived by their relatives (QSCC). Next steps are to determine the predictive utility of MBI in SCD, and its relation to incident cognitive decline over time.

A dearth of population-based epidemiological research examines neuropsychiatric symptom (NPS) in sub-clinical populations across the spectrum from normal aging to mild cognitive impairment (MCI). The construct of mild behavioral impairment (MBI) describes the emergence of sustained and impactful NPS in advance of or in combination with MCI. This is the first epidemiological study to operationalize the recently published diagnostic criteria for MBI and determine prevalence estimates across the spectrum from cognitively normal to MCI.

MBI was assessed in 1,377 older (age range 72–79 years; 52% male; MCI ;= 133; cognitively normal, but-at-risk = 397; cognitively healthy = 847). MBI was assessed in accordance with the ISTAART-AA diagnostic criteria for MBI using the neuropsychiatric inventory.

34.1% of participants met the criteria for MBI. High prevalence of MBI across the cognitive spectrum was reported (48.9% vs. 43.1% vs. 27.6%). Irrespective of level of cognitive impairment, impulse dyscontrol (33.8% vs. 28.7% vs. 17.2%) and decreased motivation (32.3% vs. 26.2% vs. 16.3%) were the most frequently met MBI domains. MBI was more prevalent in men (χ2 = 4.98, p = 0.026), especially the domains of decreased motivation and impulse dyscontrol.

This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.

Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research.

Existing literature in prodromal and dementia states was reviewed, focusing on epidemiology, and neurobiology. Search terms included: “mild cognitive impairment,” “dementia,” “prodromal dementia,” “preclinical dementia,” “Alzheimer's,” “depression,” “dysphoria,” “mania,” “euphoria,” “bipolar disorder,” and “irritability.”

Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset.

Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.