Linking cognitive and behavioral reserve: Evidence from the CAN-PROTECT study.

INTRODUCTION: Changes to the brain due to Alzheimer's disease and other age-related neuropathologies may present with cognitive and behavioral symptoms, even during preclinical and prodromal stages. While cognitive reserve is known to mitigate cognitive decline in the preclinical stages of Alzheimer's disease, links between cognitive reserve and behavioral symptoms remain unclear. This study investigates the relationship between cognitive reserve and mild behavioral impairment (MBI), a neurodegenerative behavioral prodrome. METHODS: We analyzed cross-sectional data from 1204 participants in the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN-PROTECT) study. A cognitive reserve score (CRS) was generated based on education, occupation, and personal cognitive reserve proxies. MBI presence (MBI+) and MBI global and domain symptom severity were evaluated using the self-reported MBI Checklist. Initial analyses examined the convergent validity of the CRS through associations with objective neuropsychological test performance and self-reported cognitive symptoms (Everyday Cognition [ECog-II] scale). Models were also fitted to assess MBI status and severity as functions of the CRS. RESULTS: Higher CRS was associated with better neuropsychological test scores, lower odds of subjective cognitive decline (OR = 0.86, 95% CI: [0.76, 0.98], p = .03), and lower ECog-II total score. Likewise, higher CRS was associated with lower odds of MBI+ (OR = 0.81, 95% CI: [0.71, 0.93], p = .003), and lower MBI symptom severity globally, and in impulse dyscontrol and social inappropriateness domains. DISCUSSION: We provide preliminary evidence that engagement in activities known to preserve cognitive function in aging and disease may also preserve behavioral function. Future research should disentangle possible pathways through which cognitive reserve may preserve both cognition and behavior, explore common etiologies for these symptoms, and observe outcomes longitudinally to better understand these relationships. Highlights: Education, occupation, and personal activities are cognitive reserve proxies.Cognitive reserve is linked to lower subjective cognitive decline in older persons.Cognitive reserve is linked to lower mild behavioral impairment odds and severity.

Assessment of patient life engagement in schizophrenia using items from the Positive and Negative Syndrome Scale.

BACKGROUND: Improved patient life engagement is a meaningful treatment goal in schizophrenia that cannot be satisfactorily measured using existing tools. This research aimed to determine whether certain items from the Positive and Negative Syndrome Scale (PANSS) can assess patient life engagement in schizophrenia. METHODS: Three approaches were used to identify PANSS items that reflect patient life engagement: (1) a panel discussion with expert psychiatrists (n = 4); (2) interviews with patients with schizophrenia (n = 20); and (3) a principal component analysis to explore clustering of items (n = 954 from three randomized controlled trials). Internal consistency was assessed by Cronbach's alpha and item-total correlations. A minimal clinically important difference (MCID) was determined by anchor- and distribution-based methods. RESULTS: Expert psychiatrists identified 11 relevant items, and patients rated 13 items as "very relevant" to patient life engagement, most of which clustered in the principal component analysis. Considering all results, a composite set of 14 PANSS items that may be relevant to patient life engagement in schizophrenia was devised: P2, N1, N2, N3, N4, N5, N6, N7, G6, G7, G11, G13, G15, G16 (Cronbach's alpha, 0.84; item-total correlations, 0.35-0.56, indicating acceptable correlation with the underlying concept; exception: G6 [depression], 0.19). An MCID of 5 points (small/moderate improvement) or 10 points (large improvement) may be appropriate. CONCLUSIONS: A subset of 14 PANSS items may be used to reflect patient life engagement in clinical practice/trials in schizophrenia, complementing the results of traditional psychiatric symptom scales with a patient-centered outcome that is relevant to real-world treatment goals.

Are Opioids Agitating? A Data Analysis of Baseline Data from the STAN Study.

 Agitation, a common dementia symptom often arising from untreated pain, lacks comprehensive research on its connection with opioids prescribed for long-term pain. This study investigated the relationship between opioid use and agitation in dementia patients. Participants (n = 188) were categorized into opioid, acetaminophen PRN, or no-pain medication groups. Despite higher reported pain levels in the opioid group, no significant differences in agitation were observed among the groups. In conclusion, opioid use for pain management in older adults with dementia did not significantly impact agitation, emphasizing the ongoing importance of proper pain management in improving dementia care and addressing agitation in this population.

The mind and motion: exploring the interplay between physical activity and Mild Behavioral Impairment in dementia-free older adults.

Physical inactivity in mid-life is a modifiable risk factor for dementia. Mild behavioral impairment (MBI) is a marker of potential neurodegenerative disease. We investigated the association between physical activity and MBI. Baseline data from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behaviour, Function, and Caregiving in Aging (CAN-PROTECT) were used. Four categories of weekly physical activity (cardiovascular, mind-body, strength training, and physical labour) were derived from the Community Healthy Activities Model Program for Seniors questionnaire. MBI was measured using the MBI-Checklist. Multivariable negative binomial regressions modelled the association between the standardized physical activity duration and MBI severity, adjusted for age, sex, education, marital status, ethno cultural origin, occupation, hypertension, dyslipidemia, mobility, and body mass index. Every 1 SD increase in cardiovascular activity was associated with 8.42% lower MBI severity. In contrast, every 1 SD increase in physical labor duration was associated with 5.64% greater MBI severity. These associations were neither moderated by the frequency engaging in each physical activity nor by sex. Cardiovascular physical activity in older persons may reduce levels of non-cognitive dementia markers like MBI, comparable to effects seen in cognition, potentially modulating dementia risk.

Mild Behavioral Impairment and Quality of Life in Community Dwelling Older Adults.

OBJECTIVES: Mild behavioral impairment (MBI) is a dementia risk indicator in older adults characterized by later-life emergent and persistent neuropsychiatric symptoms. Quality of life (QoL) is a multi-dimensional concept encompassing physical, spiritual, and emotional well-being. QoL aims to measure and quantify perceptions of individual health, well-being, standard of living, personal fulfillment, and satisfaction. As MBI symptoms may arise from early-stage neurodegenerative disease, MBI may contribute to declining QoL before dementia onset. In this study, we investigated the relationship between symptoms of MBI and QoL in older adults. METHODS: The sample comprised 1107 individuals aged ≥ 50 years from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN-PROTECT). Multivariable linear regressions were used to model the associations between MBI symptom severity (exposure), measured using the MBI Checklist (MBI-C), and QoL (outcome) assessed by the EuroQol-5D (EQ-5D, higher score = poorer QoL) and the novel Quality of Life and Function Five Domain Scale (QFS-5) (QFS-5, lower score = poorer QoL). Covariates were age, sex, cognition, education, ethnocultural origin, marital status, employment status, high blood pressure, heart disease, and diabetes. Moderation analysis explored potential sex differences. A sensitivity analysis was performed removing anxiety/depression items from the EQ-5D score. RESULTS: Across the sample (mean age = 64.4 ± 7.2, 79.4% female) every 1-point increase in MBI-C score was associated with a 0.06-point standard deviation (SD) increase in EQ-5D score (95% confidence interval (CI): 0.05-0.06, p < 0.001) and 0.08 SD decrease in QFS-5 score (95% CI: -0.09 to -0.08, p < 0.001). Neither association depended on sex (p = 0.59 and p = 0.41, respectively). The association remained significant after removing anxiety/depression items from the EQ-5D score (ß = 0.04, 95% CI: 0.03- 0.04, p < 0.001). CONCLUSIONS: The study shows that MBI is associated with poorer QoL, independent of sex, on two QoL scales. We addressed depression/anxiety items in the EQ-5D as a potential confounder for the observed MBI-QoL association by conducting a sensitivity analysis that excluded those items from the EQ-5D total score and by employing a novel measure of QoL (QFS-5) that excludes psychiatric symptoms from measurement of QoL. Associations of MBI with the novel QFS-5 were similar to associations between MBI and the EQ-5D. Finding interventions to reduce the burden of MBI symptoms might improve quality of life.

The effect of study partner characteristics on the reporting of neuropsychiatric symptoms across the neurocognitive spectrum.

OBJECTIVES: 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). DESIGN, SETTING, AND PARTICIPANTS: 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). MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

HarmonyTM: multi-center data harmonization applied to distributed learning for Parkinson's disease classification.

Purpose: Distributed learning is widely used to comply with data-sharing regulations and access diverse datasets for training machine learning (ML) models. The traveling model (TM) is a distributed learning approach that sequentially trains with data from one center at a time, which is especially advantageous when dealing with limited local datasets. However, a critical concern emerges when centers utilize different scanners for data acquisition, which could potentially lead models to exploit these differences as shortcuts. Although data harmonization can mitigate this issue, current methods typically rely on large or paired datasets, which can be impractical to obtain in distributed setups. Approach: We introduced HarmonyTM, a data harmonization method tailored for the TM. HarmonyTM effectively mitigates bias in the model's feature representation while retaining crucial disease-related information, all without requiring extensive datasets. Specifically, we employed adversarial training to "unlearn" bias from the features used in the model for classifying Parkinson's disease (PD). We evaluated HarmonyTM using multi-center three-dimensional (3D) neuroimaging datasets from 83 centers using 23 different scanners. Results: Our results show that HarmonyTM improved PD classification accuracy from 72% to 76% and reduced (unwanted) scanner classification accuracy from 53% to 30% in the TM setup. Conclusion: HarmonyTM is a method tailored for harmonizing 3D neuroimaging data within the TM approach, aiming to minimize shortcut learning in distributed setups. This prevents the disease classifier from leveraging scanner-specific details to classify patients with or without PD-a key aspect for deploying ML models for clinical applications.

Modeling the progression of neuropsychiatric symptoms in Alzheimer's disease with PET-based Braak staging.

In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum. Participants were assigned a Braak stage at baseline and followed for 1.97 (s.d. 0.62) years. NPS were investigated using the Mild Behavioral Impairment Checklist (MBI-C) and the Neuropsychiatric Inventory Questionnaire severity (NPI-Q-S) and distress (NPI-Q-D) scales. Multiple linear regressions (MLR) assessed the association of Braak stages with baseline NPS and the annual change in NPS scores. At baseline, stages I-II, III-IV, and V-VI were associated with higher MBI-C, NPI-Q-S, and NPI-Q-D scores. Stages V-VI were associated with a significant annual increase in MBI-C scores. These findings suggest that tau accumulation may manifest clinically with an increase in NPS, which seems to be an early event in AD pathophysiology. Moreover, PET-based Braak staging appears to be a good predictor of NPS severity progression.

Neuropsychiatric symptoms: Risk factor or disease marker? A study of structural imaging biomarkers of Alzheimer's disease and incident cognitive decline.

Neuropsychiatric symptoms (NPS) are risk factors for Alzheimer's disease (AD) but can also manifest secondary to AD pathology. Mild behavioral impairment (MBI) refers to later-life emergent and persistent NPS that may mark early-stage AD. To distinguish MBI from NPS that are transient or which represent psychiatric conditions (non-MBI NPS), we investigated the effect of applying MBI criteria on NPS associations with AD structural imaging biomarkers and incident cognitive decline. Data for participants (n = 1273) with normal cognition (NC) or mild cognitive impairment (MCI) in the National Alzheimer's Coordinating Center Uniform Data Set were analyzed. NPS status (MBI, non-MBI NPS) was derived from the Neuropsychiatric Inventory Questionnaire and psychiatric history. Normalized measures of bilateral hippocampal (HPC) and entorhinal cortex (EC) volume, and AD meta-region of interest (ROI) mean cortical thickness were acquired from T1-weighted magnetic resonance imaging scans. Multivariable linear and Cox regressions examined NPS associations with imaging biomarkers and incident cognitive decline, respectively. MBI was associated with lower volume and cortical thickness in all ROIs in both NC and MCI, except for EC volume in NC. Non-MBI NPS were only associated with lower HPC volume in NC. Although both of the NPS groups showed higher hazards for MCI/dementia than No NPS, MBI participants showed more rapid decline. Although both types of NPS were linked to HPC atrophy, only NPS that emerged and persisted in later-life, consistent with MBI criteria, were related to AD neurodegenerative patterns beyond the HPC. Moreover, MBI predicted faster progression to dementia than non-MBI NPS.

Associations between white and grey matter damage and gait impairment in cerebral amyloid angiopathy.

BACKGROUND: Cerebral amyloid angiopathy (CAA) is associated with white matter damage and neurodegeneration. Gait is impaired in CAA; however, the neural basis of this impairment is unclear. RESEARCH QUESTION: Are gait impairments in patients with CAA associated with altered cerebral white matter diffusivity and/or atrophy of cortical and subcortical grey matter. METHODS: Participants with CAA (n=29), Alzheimer's disease (AD; n=16), and normal controls (n=47) were included. Gait was assessed using a 6 m walkway with parameters categorized into rhythm, pace, postural control, and variability domains. The dual-task cost (DTC) of gait speed was calculated for counting backwards, animal fluency, and serial sevens tasks. Whole-brain white matter disruption was quantified using the peak width of skeletonized mean diffusivity (PSMD), and thickness and volume of select cortical, subcortical, and cerebellar regions were quantified using FreeSurfer. RESULTS: In CAA participants, associations were found between PSMD and pace (standardized parameter estimate (ß), 95 % confidence interval (CI): 0.17, 0.03-0.32), and medial orbital frontal cortical thickness and counting backwards DTC (parameter estimate (PE), 95 % CI: -5.7 %/SD, -0.24 to -11.23). Across all groups, including CAA, associations were found between PSMD and pace, variability, counting backwards DTC, and animal fluency DTC; between frontal cortical thickness and pace, counting backwards DTC, and animal fluency DTC; between cortical regions affected by AD (inferior parietal cortex, inferior and middle temporal gyrus) and counting backwards DTC; and between thalamus volume and postural control. SIGNIFICANCE: Reduced white matter structural integrity and grey matter loss is associated with poor overall gait performance in CAA, AD, and normal controls.

Prevalence of psychotic symptoms in mild cognitive impairment: A systematic review and meta-analysis.

INTRODUCTION: Neuropsychiatric symptoms may impact prognosis in individuals with mild cognitive impairment (MCI); however, data on frequency of psychotic symptoms are sparse. METHODS: We searched MEDLINE, EMBASE, PsychoINFO from inception to June 2023. We included studies reporting patients with MCI prevalence of (delusions and/or hallucinations. Random effects model were performed to estimate the prevalence, and subgroup and meta-regression analyses were performed to explore heterogeneity. RESULTS: Of 3145 records identified, 36 studies were included, enrolling 20,426 patients. Overall prevalence of hallucinations was 1.78 % (95 % CI, 1.17 - 2.71) and delusions 3.84 % (95 % CI, 2.71 - 5.42), both with significant heterogeneity (/2 = 90 %). Prevalence of hallucinations and delusions were lower when measured by NPI scales and in population-based samples. DISCUSSION: Delusions and hallucinations occur in MCI patients at low rates. Prevalence can be partially explained by the assessment method, sample source and study heterogeneity.

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.

Psychosis detection in dementia: a systematic review of diagnostic test accuracy studies.

Introduction: Symptoms of psychosis, characterized by delusions and hallucinations, are commonly experienced by persons living with dementia. A systematic review was completed to identify tools to evaluate symptoms of psychosis compared to a reference standard in persons with dementia. Articles reporting correlation values between psychosis tools were also identified. Methods: The search concepts psychosis, dementia, and diagnostic accuracy were used to search MEDLINE, PsycINFO, and Embase. Included articles meeting the primary objective described a tool to assess symptoms of psychosis, delusions, or hallucinations in persons with dementia, a reference standard form of diagnostic assessment for psychosis, and diagnostic accuracy outcomes for the psychosis tool. Secondary objective articles reported correlation values between two or more psychosis tools in persons with dementia. Results: One study met the primary objective and described the sensitivity and specificity of the Neuropsychiatric Inventory (NPI) and Columbia University Scale for Psychopathology in Alzheimer's Disease (CUSPAD) in identifying symptoms of psychosis, hallucinations, and delusions. The sensitivity of the NPI and CUSPAD in identifying symptoms of psychosis was 83 and 90%, respectively. Nine studies meeting the secondary objective described eleven unique tools and examined the degree to which tools used to assess psychotic symptoms in persons with dementia were related. Discussion: The NPI and CUSPAD were identified in a single study as psychosis tools that have been evaluated against a reference standard of psychosis assessment in persons with dementia. Various tools to assess the burden of psychotic symptoms in persons with dementia exist, but the diagnostic accuracy of existing tools remains understudied. Further research on the comparative utility and diagnostic accuracy is required for all psychosis tools used with persons with dementia.

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.

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.

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.

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%.

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.

Guideline Recommendations on Behavioral and Psychological Symptoms of Dementia: A Systematic Review.

OBJECTIVE: To synthesize recommendations on assessing and managing behavioral and psychological symptoms of dementia (BPSDs) in existing clinical practice guidelines on dementia care to learn from and adapt recommendations to a Canadian context and language for describing BPSDs. DESIGN: Systematic review. SETTING AND PARTICIPANTS: Moderate to high-quality clinical practice guidelines on dementia care that made 1 or more recommendations on BPSD assessment or management. METHODS: We searched MEDLINE, Embase, JBI EBM, PsycINFO, AgeLine, and gray literature for clinical practice guidelines on dementia care making recommendations on BPSD, published between January 1, 2011, and October 13, 2022. Two independent reviewers conducted study screening and data abstraction. Four independent reviewers completed quality appraisal using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool; included guidelines had a mean overall AGREE II score ≥4. RESULTS: Our systematic review identified 23 moderate to high-quality clinical practice guidelines (264 recommendations). The mean overall quality score on the AGREE II tool ranged from 4 to 6.5. Recommendations were clearly presented (mean clarity of presentation score 73.5%), but guideline applicability was not consistently addressed (mean applicability score 39.3%). BPSD was the most prevalent term describing neuropsychiatric symptoms (number of guidelines [n] = 14). People with lived experience contributed to 6 guidelines (26.1%). Ten guidelines (43.5%) described 1 or more health equity considerations. Guidelines made recommendations for assessing and managing agitation (n = 12), aggression (n = 10), psychosis (n = 11), depression (n = 9), anxiety (n = 5), apathy (n = 6), inappropriate sexual behavior (n = 3), nighttime behavior (n = 5), and eating disturbances (n = 3). There was substantial variability in recommendation statements, evidence quality assigned to each statement, and strength of recommendations. CONCLUSIONS AND IMPLICATIONS: There are several moderate to high-quality clinical practice guidelines making recommendations on BPSD assessment and management, but variability in recommendation statements across guidelines and insufficient consideration of guideline applicability may hamper guideline dissemination and implementation in clinical practice.

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.