White Matter Microstructural Underpinnings of Mild Behavioral Impairment in Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) experience changes in behavior, personality, and cognition that can manifest even in the initial stages of the disease. Previous studies have suggested that mild behavioral impairment (MBI) should be considered an early marker of cognitive decline. However, the precise neurostructural underpinnings of MBI in early- to mid-stage PD remain poorly understood. OBJECTIVE: The aim was to explore the changes in white matter microstructure linked to MBI and mild cognitive impairment (MCI) in early- to mid-stage PD using diffusion magnetic resonance imaging (dMRI). METHODS: A total of 91 PD patients and 36 healthy participants were recruited and underwent anatomical MRI and dMRI, a comprehensive neuropsychological battery, and the completion of the Mild Behavioral Impairment-Checklist. Metrics of white matter integrity included tissue fractional anisotropy (FAt) and radial diffusivity (RDt), free water (FW), and fixel-based apparent fiber density (AFD). RESULTS: The connection between the left amygdala and the putamen was disrupted when comparing PD patients with MBI (PD-MBI) to PD-non-MBI, as evidenced by increased RDt (η2 = 0.09, P = 0.004) and both decreased AFD (η2 = 0.05, P = 0.048) and FAt (η2 = 0.12, P = 0.014). Compared to controls, PD patients with both MBI and MCI demonstrated increased FW for the connection between the left orbitofrontal gyrus (OrG) and the hippocampus (η2 = 0.22, P = 0.008), augmented RDt between the right OrG and the amygdala (η2 = 0.14, P = 0.008), and increased RDt (η2 = 0.25, P = 0.028) with decreased AFD (η2 = 0.10, P = 0.046) between the right OrG and the caudate nucleus. CONCLUSION: MBI is associated with abnormal microstructure of connections involving the orbitofrontal cortex, putamen, and amygdala. To our knowledge, this is the first assessment of the white matter microstructure in PD-MBI using dMRI. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Presenilin Gene Mutation-associated Psychosis: Phenotypic Characteristics and Clinical Implications.

Although psychotic symptoms have been described in association with rare presenilin ( PSEN ) gene mutations underlying early-onset Alzheimer disease (AD), no contemporary reviews on this topic exist. The purpose of this review is to characterize the psychiatric phenotype (specifically with respect to psychosis) of PSEN1 and PSEN2 variant-associated AD. A PubMed search was completed in July 2023. Only articles that described individuals harboring a PSEN1 or PSEN2 mutation who experienced symptoms of psychosis were included in the review. Thirty-three articles describing 52 individuals were included in the review, as well as one other study that provided limited information pertaining to an additional 21 cases. While visual hallucinations were the most common psychotic symptom, followed by persecutory delusions, auditory hallucinations occurred in ~17% of individuals. In ~33% of the reviewed cases psychotic symptoms were present at or near disease onset, and 9 of these individuals experienced auditory hallucinations and/or delusions in the absence of visual hallucinations (~17% of all cases). In many cases, symptoms developed at a relatively young age. As presenilin gene variant-associated psychosis may resemble a primary psychotic disorder, clinicians should be vigilant with respect to screening for signs/symptoms suggestive of neurodegeneration in first-episode psychosis.

Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Detection of anxiety symptoms and disorders in older adults: a diagnostic accuracy systematic review.

BACKGROUND: Anxiety symptoms and disorders are common in older adults and often go undetected. A systematic review was completed to identify tools that can be used to detect anxiety symptoms and disorders in community-dwelling older adults. METHODS: MEDLINE, Embase and PsycINFO were searched using the search concepts anxiety, older adults and diagnostic accuracy in March 2023. Included articles assessed anxiety in community-dwelling older adults using an index anxiety tool and a gold standard form of anxiety assessment and reported resulting diagnostic accuracy outcomes. Estimates of pooled diagnostic accuracy outcomes were completed. RESULTS: Twenty-three anxiety tools were identified from the 32 included articles. Pooled diagnostic accuracy outcomes were estimated for the Geriatric Anxiety Inventory (GAI)-20 [n = 3, sensitivity = 0.89, 95% confidence interval (CI) = 0.70-0.97, specificity = 0.80, 95% CI = 0.67-0.89] to detect generalized anxiety disorder (GAD) and for the GAI-20 (n = 3, cut off ≥ 9, sensitivity = 0.74, 95% CI = 0.62-0.83, specificity = 0.96, 95% CI = 0.74-1.00), Beck Anxiety Inventory (n = 3, sensitivity = 0.70, 95% CI = 0.58-0.79, specificity = 0.60, 95% CI = 0.51-0.68) and Hospital Anxiety and Depression Scale (HADS-A) (n = 3, sensitivity = 0.78, 95% CI = 0.60-0.89, specificity = 0.76, 95% CI = 0.60-0.87) to detect anxiety disorders in clinical samples. CONCLUSION: The GAI-20 was the most studied tool and had adequate sensitivity while maintaining acceptable specificity when identifying GAD and anxiety disorders. The GAI-20, GAI-Short Form and HADS-A tools are supported for use in detecting anxiety in community-dwelling older adults. Brief, self-rated and easy-to-use tools may be the best options for anxiety detection in community-dwelling older adults given resource limitations. Clinicians may consider factors including patient comorbidities and anxiety prevalence when selecting a tool and cut off.

Adjunctive Brexpiprazole for Patient Life Engagement in Major Depressive Disorder: A Canadian, Phase 4, Open-Label, Interventional Study: Brexpiprazole d'appoint pour l'engagement dans la vie des patients souffrant de trouble dépressif majeur: une étude interventionnelle canadienne ouverte de phase 4.

OBJECTIVES: To characterize the effects of adjunctive brexpiprazole on patient life engagement and depressive symptoms in patients with major depressive disorder (MDD) using patient-reported outcomes. METHODS: An 8-week, Phase 4, open-label, interventional study was conducted at 15 Canadian trial sites between April 2021 and May 2022. Adult outpatients with MDD (at least moderately severe) and inadequate response to 1-2 antidepressants continued their current antidepressant and received oral adjunctive brexpiprazole 0.5-2 mg/day. Co-primary endpoints were change from baseline to Week 8 in Inventory of Depressive Symptomatology Self-Report (IDS-SR) 10-item Life Engagement subscale score, and IDS-SR 30-item total score. Safety was assessed by standard variables. RESULTS: Of 122 enrolled patients, 120 (98.4%) were treated (mean [SD] dose: 1.2 [0.4] mg/day) and analyzed, and 111 (91.0%) completed the study. Statistically significant least squares mean improvements to Week 8 were observed on IDS-SR10 Life Engagement subscale score (baseline mean [SD]: 16.1 [4.7]; change [95% confidence interval]: -8.11 [-9.34, -6.88]; p < 0.001) and IDS-SR total score (baseline mean [SD]: 41.3 [9.8]; change [95% confidence interval]: -17.38 [-20.08, -14.68]; p < 0.001). Improvements were observed from Week 2, onwards. Treatment-emergent adverse events with incidence ≥5% were fatigue (n = 13, 10.8%), headache (n = 13, 10.8%), insomnia (n = 12, 10.0%), nausea (n = 9, 7.5%), tremor (n = 8, 6.7%), and weight increase (n = 7, 5.8%). Six patients (5.0%) discontinued due to adverse events. Mean (SD) change in body weight from baseline to last visit was +1.9 (3.4) kg. CONCLUSIONS: Using an exploratory patient-reported outcome measure, patients with MDD and inadequate response to antidepressants who received open-label adjunctive brexpiprazole showed early and clinically meaningful improvement in patient life engagement, which should be further assessed in a prospective randomized controlled trial. Patient-rated depressive symptoms (on the validated 30-item IDS-SR) also improved. Adjunctive brexpiprazole was well tolerated, and no new safety signals were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04830215.

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

Reduction and prevention of agitation in persons with neurocognitive disorders: an international psychogeriatric association consensus algorithm.

OBJECTIVES: 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). DESIGN: Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion. SETTING: IPA Agitation Workgroup. PARTICIPANTS: IPA panel of international experts on agitation. INTERVENTION: Integration of available information into a comprehensive algorithm. MEASUREMENTS: None. RESULTS: 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. CONCLUSIONS: 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.

Agitation in cognitive disorders: Progress in the International Psychogeriatric Association consensus clinical and research definition.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Detecting agitation and aggression in persons living with dementia: a systematic review of diagnostic accuracy.

OBJECTIVE: 40-60% of persons living with dementia (PLWD) experience agitation and/or aggression symptoms. There is a need to understand the best method to detect agitation and/or aggression in PLWD. We aimed to identify agitation and/or aggression tools that are validated against a reference standard within the context of PLWD. METHODS: Our study was registered on PROSPERO (CRD42020156708). We searched MEDLINE, Embase, and PsycINFO up to April 22, 2024. There were no language or date restrictions. Studies were included if they used any tools or questionnaires for detecting either agitation or aggression compared to a reference standard among PLWD, or any studies that compared two or more agitation and/or aggression tools in the population. All screening and data extraction were done in duplicates. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Data extraction was completed in duplicates by two independent authors. We extracted demographic information, prevalence of agitation and/or aggression, and diagnostic accuracy measures. We also reported studies comparing the correlation between two or more agitation and/or aggression tools. RESULTS: 6961 articles were screened across databases. Six articles reporting diagnostic accuracy measures compared to a reference standard and 30 articles reporting correlation measurements between tools were included. The agitation domain of the Spanish NPI demonstrated the highest sensitivity (100%) against the agitation subsection of the Spanish CAMDEX. Single-study evidence was found for the diagnostic accuracy of commonly used agitation scales (BEHAVE-AD, NPI and CMAI). CONCLUSIONS: The agitation domain of the Spanish NPI, the NBRS, and the PAS demonstrated high sensitivities, and may be reasonable for clinical implementation. However, a limitation to this finding is that despite an extensive search, few studies with diagnostic accuracy measurements were identified. Ultimately, more research is needed to understand the diagnostic accuracy of agitation and/or aggression detection tools among PLWD.

Barriers and facilitators to care for agitation and/or aggression among persons living with dementia in long-term care.

BACKGROUND: Agitation and/or aggression affect up to 60% of persons living with dementia in long-term care (LTC). It can be treated via non-pharmacological and pharmacological interventions, but the former are underused in clinical practice. In the literature, there is currently a lack of understanding of the challenges to caring for agitation and/or aggression among persons living with dementia in LTC. This study assesses what barriers and facilitators across the spectrum of care exist for agitation and/or aggression among people with dementia in LTC across stakeholder groups. METHODS: This was a qualitative study that used semi-structured interviews among persons involved in the care and/or planning of care for people with dementia in LTC. Participants were recruited via purposive and snowball sampling, with the assistance of four owner-operator models. Interviews were guided by the Theoretical Domains Framework and transcribed and analyzed using Framework Analysis. RESULTS: Eighteen interviews were conducted across 5 stakeholder groups. Key identified barriers were a lack of agitation and/or aggression diagnostic measures, limited training for managing agitation and/or aggression in LTC, an overuse of physical and chemical restraints, and an underuse of non-pharmacological interventions. Facilitators included using an interdisciplinary team to deliver care and having competent and trained healthcare providers to administer non-pharmacological interventions. CONCLUSIONS: This study advances care for persons living with dementia in LTC by drawing attention to unique and systemic barriers present across local and national Canadian LTC facilities. Findings will support future implementation research endeavours to eliminate these identified barriers across the spectrum of care, thus improving care outcomes among people with dementia in LTC.

Comparative methods for quantifying plasma biomarkers in Alzheimer's disease: Implications for the next frontier in cerebral amyloid angiopathy diagnostics.

Plasma amyloid beta (Aß) and tau are emerging as accessible biomarkers for Alzheimer's disease (AD). However, many assays exist with variable test performances, highlighting the need for a comparative assessment to identify the most valid assays for future use in AD and to apply to other settings in which the same biomarkers may be useful, namely, cerebral amyloid angiopathy (CAA). CAA is a progressive cerebrovascular disease characterized by deposition of Aß40 and Aß42 in cortical and leptomeningeal vessels. Novel immunotherapies for AD can induce amyloid-related imaging abnormalities resembling CAA-related inflammation. Few studies have evaluated plasma biomarkers in CAA. Identifying a CAA signature could facilitate diagnosis, prognosis, and a safer selection of patients with AD for emerging immunotherapies. This review evaluates studies that compare the diagnostic test performance of plasma biomarker techniques in AD and cerebrovascular and plasma biomarker profiles of CAA; it also discusses novel hypotheses and future avenues for plasma biomarker research in CAA.

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

BACKGROUND: The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers. METHODS: Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed-effects models. RESULTS: The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation. DISCUSSION: Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment. HIGHLIGHTS: Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p. pTau could be a pharmacological target to treat agitation and psychosis symptoms. MBI domains were linked to metabolic dysregulation involving insulin and homocysteine.

A systematic review/meta-analysis of prevalence and incidence rates illustrates systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research.

We investigate Alzheimer's disease and related dementia (ADRD) prevalence, incidence rate, and risk factors in individuals racialized as Asian and/or Asian-American and assess sample representation. Prevalence, incidence rate, risk factors, and heterogeneity of samples were assessed. Random-effects meta-analysis was conducted, generating pooled estimates. Of 920 records across 14 databases, 45 studies were included. Individuals racialized as Asian and/or Asian-American were mainly from Eastern and Southern Asia, had higher education, and constituted a smaller sample relative to non-Hispanic white cohorts. The average prevalence was 10.9%, ranging from 0.4% to 46%. The average incidence rate was 20.03 (12.01-33.8) per 1000 person-years with a range of 75.19-13.59 (12.89-14.33). Risk factors included physiological, genetic, psychological, behavioral, and social factors. This review underscores the systemic underrepresentation of individuals racialized as Asian and/or Asian-American in ADRD research and the need for inclusive approaches accounting for culture, language, and immigration status. HIGHLIGHTS: There is considerable heterogeneity in the prevalence of ADRD among studies of Asian-Americans. There is limited data on group-specific risk factors for ADRD among Asian-Americans. The average prevalence of (ADRD) among Asian-Americans was found to be 7.4%, with a wide range from 0.5% to 46%.

Facilitators and Barriers Influencing Antipsychotic Medication Prescribing and Deprescribing Practices in Critically Ill Adult Patients: a Qualitative Study.

BACKGROUND: Antipsychotic medications do not alter the incidence or duration of delirium, but these medications are frequently prescribed and continued at transitions of care in critically ill patients when they may no longer be necessary or appropriate. OBJECTIVE: The purpose of this study was to identify and describe relevant domains and constructs that influence antipsychotic medication prescribing and deprescribing practices among physicians, nurses, and pharmacists that care for critically ill adult patients during and following critical illness. DESIGN: We conducted qualitative semi-structured interviews with critical care and ward healthcare professionals including physicians, nurses, and pharmacists to understand antipsychotic prescribing and deprescribing practices for critically ill adult patients during and following critical illness. PARTICIPANTS: Twenty-one interviews were conducted with 11 physicians, five nurses, and five pharmacists from predominantly academic centres in Alberta, Canada, between July 6 and October 29, 2021. MAIN MEASURES: We used deductive thematic analysis using the Theoretical Domains Framework (TDF) to identify and describe constructs within relevant domains. KEY RESULTS: Seven TDF domains were identified as relevant from the analysis: Social/Professional role and identity; Beliefs about capabilities; Reinforcement; Motivations and goals; Memory, attention, and decision processes; Environmental context and resources; and Beliefs about consequences. Participants reported antipsychotic prescribing for multiple indications beyond delirium and agitation including patient and staff safety, sleep management, and environmental factors such as staff availability and workload. Participants identified potential antipsychotic deprescribing strategies to reduce ongoing antipsychotic medication prescriptions for critically ill patients including direct communication tools between prescribers at transitions of care. CONCLUSIONS: Critical care and ward healthcare professionals report several factors influencing established antipsychotic medication prescribing practices. These factors aim to maintain patient and staff safety to facilitate the provision of care to patients with delirium and agitation limiting adherence to current guideline recommendations.

Validating the Mild Behavioral Impairment Checklist in a Cognitive Clinic: Comparisons With the Neuropsychiatric Inventory Questionnaire.

OBJECTIVE: To compare the utility of the Mild Behavioral Impairment-Checklist (MBI-C) and Neuropsychiatric Inventory Questionnaire (NPI-Q) to capture NPS in subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. METHODS: In this cross-sectional memory clinic study, linear regression models compared MBI-C (n = 474) and NPI-Q (n = 1040) scores in relation to Montreal Cognitive Assessment (MoCA) score. RESULTS: MBI prevalence was 37% in subjective cognitive decline, 54% in mild cognitive impairment, and 62% in dementia. Worse diagnostic status was associated with higher MBI-C and NPI-Q score (P < .001), lower MoCA (P < .001), and greater age (P < .001). Higher MBI-C (ß -.09; 95% CI -.13, -.05) and NPI-Q (ß -.17; 95% CI -.23, -.10) scores were associated with lower MoCA scores, with psychosis most strongly associated (ß -1.11; 95% CI -1.56, -.65 vs ß -1.14; 95% CI -1.55, -.73). CONCLUSIONS: The MBI-C captures global and domain-specific NPS across cognitive stages. Both the MBI-C and NPI-Q have utility in characterizing NPS.

Reliability and Validity of the Traditional Chinese Version of the Mild Behavioral Impairment - Checklist Among Persons With Mild Cognitive Impairment - A Validation Study.

OBJECTIVE: To evaluate the reliability and validity of the traditional Chinese version of the Mild Behavioral Impairment Checklist (MBI-C) among Hong Kong Chinese with mild cognitive impairment (MCI). METHODS: A total of 172 participants were recruited from 2 community facilities. Cronbach's alpha (α) was calculated to evaluate internal consistency. Intra-class correlation coefficient (ICC) was used to measure 2-week test-retest reliability. Construct validity was evaluated by conducting exploratory factor analysis to identify the internal structure of MBI-C, and assessing the correlation between theoretically related constructs, including objective and subjective cognitive impairment, neurotic personality, social supports, and maladaptive coping. Concurrent validity was assessed by its correlation with Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: The results revealed good internal consistency and test-retest reliability of the MBI-C. Item analysis identified 4 items with low item-to-total correlations. The EFA identified a seven-factor structure. Hypothesis testing identified its significant correlations with subjective cognitive impairment, neurotic personality, social supports, and maladaptive coping. Concurrent validity was supported by its significant correlation with the NPI-Q. CONCLUSIONS: The traditional Chinese version of MBI-C is a valid and reliable outcome measure to assess the severity of neuropsychiatric symptoms of the MCI population.

Distinguishing apathy from depression: A review differentiating the behavioral, neuroanatomic, and treatment-related aspects of apathy from depression in neurocognitive disorders.

OBJECTIVES: This narrative review describes the clinical features of apathy and depression in individuals with neurocognitive disorders (NCDs), with the goal of differentiating the two syndromes on the basis of clinical presentation, diagnostic criteria, neuropathological features, and contrasting responses to treatments. METHODS: Literature was identified using PubMed, with search terms to capture medical conditions of interest; additional references were also included based on our collective experience and knowledge of the literature. RESULTS: Evidence from current literature supports the distinction between the two disorders; apathy and depression occur with varying prevalence in individuals with NCDs, pose different risks of progression to dementia, and have distinct, if overlapping, neurobiological underpinnings. Although apathy is a distinct neuropsychiatric syndrome, distinguishing apathy from depression can be challenging, as both conditions may occur concurrently and share several overlapping features. Apathy is associated with unfavorable outcomes, especially those with neurodegenerative etiologies (e.g., Alzheimer's disease) and is associated with an increased burden for both patients and caregivers. Diagnosing apathy is important not only to serve as the basis for appropriate treatment, but also for the development of novel targeted interventions for this condition. Although there are currently no approved pharmacologic treatments for apathy, the research described in this review supports apathy as a distinct neuropsychiatric condition that warrants specific treatments aimed at alleviating patient disability. CONCLUSIONS: Despite differences between these disorders, both apathy and depression pose significant challenges to patients, their families, and caregivers; better diagnostics are needed to develop more tailored treatment and support.

Health System Change for Alzheimer's Disease-Modifying Therapies in Canada: Beginning the Discussion.

Alzheimer's disease (AD) is a neurodegenerative disorder that accounts for 60%-70% of patients with dementia, and it is estimated that over one million Canadians will be living with dementia by 2030. Disease-modifying therapies (DMTs) targeting the underlying pathophysiology of AD are currently in development. Several models have demonstrated that the potential arrival of Alzheimer's DMTs will most likely overwhelm the already-constrained Canadian healthcare system. Canada does not have a strategy to address the extensive requirements of using DMTs, including providing an early diagnosis of AD, confirming DMT eligibility via amyloid biomarkers, and conducting ongoing treatment monitoring. Thus, a multidisciplinary group of experts involved in AD care in Canada gathered to review (1) the current barriers to diagnosis and management of AD; (2) how existing clinic models, including those used in multiple sclerosis (MS), could be applied to address key barriers in AD; and (3) how to design and implement optimal care pathways in the future. The actions outlined in this review will help clinicians and healthcare systems improve readiness to integrate the use of disease-modifying therapies in Alzheimer's disease, if such therapies are approved in Canada.

Preliminary Validation Study of the French-Quebec Version of the Mild Behavioral Impairment Checklist.

BACKGROUND: Alzheimer disease dementia may be preceded by cognitive stages during which behavioral and psychological changes can occur. More precisely, behavioral symptoms may be observed during the subjective cognitive decline (SCD) or the mild cognitive impairment (MCI) stages; these symptoms can be measured using the Mild Behavioral Impairment Checklist (MBI-C). OBJECTIVE: To validate the French-Quebec version of the MBI-C in individuals ages 60-85 years. METHOD: The sample included 60 participants (20 MCI, 20 SCD, 20 cognitively healthy) and their informants. To assess the discriminant validity of the MBI-C, a Kruskal-Wallis analysis with a multiple comparisons test was performed on the MBI-C Total score. To determine convergent validity, Spearman correlations were calculated between the MBI-C subscales and a set of validation tools. Finally, test-retest reliability was assessed with Spearman correlations of MBI-C scores between two test sessions. RESULTS: All of the analyses indicated satisfactory psychometric properties for the French-Quebec version of the MBI-C. CONCLUSION: This validation study reveals that the MBI-C can be used successfully in dementia risk assessments. From now on, the use of a validated MBI-C will be possible in the French-Quebec population.