Sex Differences in Neuropsychiatric Symptoms in Alpha-Synucleinopathies: A Systematic Review and Meta-Analysis.

BACKGROUND: Alpha-synucleinopathies, such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), demonstrate sex differences with regard to prevalence, age of onset, and motor manifestations. Neuropsychiatric symptoms (NPS) are common early and late manifestations of these disorders. OBJECTIVES: We aimed to describe sex differences in NPS across alpha-synucleinopathies. METHODS: We searched Web of Science Core collection databases to identify observational studies published between January 1, 2000, and June 1, 2022, reporting the prevalence or severity of NPS among individuals with a diagnosis of PD, PDD, or DLB. Prevalence and severity were pooled for each NPS according to sex using random-effects models. RESULTS: Two-hundred-and-forty studies, representing 796,026 participants (45% females), were included in the meta-analysis. Female sex was associated with a higher prevalence of anxiety (OR = 1.60 [95% CI: 1.40, 1.82]), depression (OR = 1.56 [1.45, 1.67]), fatigue (OR = 1.21 [1.02, 1.43]), and psychotic symptoms (OR = 1.26 [1.14, 1.40]) and more severe anxiety (g = 1.35 [95% CI: 0.58, 2.13]), depression (g = 1.57 [1.05, 2.08]), and fatigue (g = 0.86 [0.41, 1.32]), while male sex was associated with a higher prevalence of apathy (OR = 0.77 [0.63, 0.93]), impulse control disorders (OR = 0.67 [0.55, 0.82]), REM sleep behavior disorder (OR = 0.54 [0.42, 0.70]), hypersomnolence (OR = 0.67 [0.56, 0.80]), and suicide (OR = 0.30 [0.20, 0.44]). CONCLUSIONS: NPS have different prevalences and severities in alpha-synucleinopathies according to sex. These findings support consideration of sex in the elaboration of clinical tools.

Critically Ill Older Adults' Representation in Intervention Trials: A Systematic Review.

OBJECTIVES: Older adults may be under-represented in critical care research, and results may not apply to this specific population. Our primary objective was to evaluate the prevalence of inclusion of older adults across critical care trials focused on common ICU conditions or interventions. Our secondary objective was to evaluate whether older age was used as a stratification variable for randomization or outcome analysis. DESIGN SETTING AND SUBJECTS: We performed a systematic review of previously published systematic reviews of randomized controlled trials (RCTs) in critical care. We searched PubMed, Ovid, CENTRAL, and Cochrane from 2009 to 2022. Systematic reviews of any interventions across five topics: acute respiratory distress syndrome (ARDS), sepsis/shock, nutrition, sedation, and mobilization were eligible. MAIN RESULTS: We identified 216 systematic reviews and included a total of 253 RCTs and 113,090 patients. We extracted baseline characteristics and the reported proportion of older adults. We assessed whether any upper age limit was an exclusion criterion for trials, whether age was used for stratification during randomization or data analysis, and if age-specific subgroup analysis was present. The most prevalent topic was sepsis (78 trials, 31%), followed by nutrition (62 trials, 25%), ARDS (39 trials, 15%), mobilization (38 trials, 15%), and sedation (36 trials, 14%). Eighteen trials (7%) had exclusion criteria based on older age. Age distribution with information on older adults prevalence was given in six trials (2%). Age was considered in the analysis of ten trials (5%) using analytic methods to evaluate the outcome stratified by age. Conclusions: In this systematic review, the proportion of older critically ill patients is undetermined, and it is unclear how age is or is not an effect modifier or to what extent the results are valid for older adult groups. Reporting age is important to guide clinicians in personalizing care. These results highlight the importance of incorporating older critically ill patients in future trials to ensure the results are generalizable to this growing population.

Factors Associated with Alternate Level of Care Status Designation: a Case-Control Study and Model to Optimize Care Trajectories.

Background: As health-care demand is growing, our health-care system will require the optimization of the care trajectories. Patients with an alternate level of care (ALC) status could be a target for flow optimization. We aimed to characterize ALC patients and risk factors for ALC status, and to propose an integrated model to analyze the trajectory of ALC patients and discuss solutions to reduce their burden. Methods: A case-control design was used to compare 60 ALC and 60 non-ALC patients admitted to the geriatric unit of the Centre hospitalier de l'Université de Montréal in 2021, collecting medical and sociodemographic data. Based on our model, univariate statistical analyses were computed to compare groups and identify risk factors for ALC status. Results: ALC patients were less independent (22% performed five to six activities of daily living vs. 43%, p = .03). Both groups were comparable in terms of mobility and neurocognitive disorders. ALC patients were more likely to receive a new diagnosis of a neurocognitive disorder or new behavioural or psychological symptoms (37% vs. 15%, p = .008). Up to 25% of ALC patients were admitted despite presenting no active medical condition (vs. 3% of non-ALC patients, p = .002). Conclusions: The optimization of the care trajectory of ALC patients is mainly based on pre-hospital and post-hospital factors. A proportion of ALC admissions might be avoidable with additional investment in home care resources and relocation procedures. Fluidity of ALC trajectory may benefit from improved orientation at discharge procedures. Full optimization of ALC trajectories requires a systemic understanding of the health-care system.

Systematic review of research barriers, facilitators, and stakeholders in long-term care and geriatric settings, and a conceptual mapping framework to build research capacity.

BACKGROUND: Older adults are underrepresented in research. Heterogeneity of research processes in this population, specifically in long-term care (LTC) and geriatric acute care (GAC), is not well described and may impede the design, planning, and conduct of research. In this study, we identified, quantified, and mapped stakeholders, research stages, and transversal themes of research processes, to develop a mapping framework to improve research capacity by better characterizing this heterogeneity. METHODS: Multicomponent mixed methods study. An environmental scan was used to initiate a preliminary framework. We conducted a systematic literature search on processes, barriers, and methods for clinical research in GAC and LTC to extract and update stakeholders, research stages, and themes. Importance and interactions of elements were synthesized via heatmaps by number of articles, mentions, and content intersections. RESULTS: For our initial framework and environmental scan, we surveyed 24 stakeholders. Of 9277 records, 68 articles were included in our systematic review and allowed us to identify 12 stakeholders, 13 research stages, 17 transversal themes (either barriers, facilitators, general themes, or recommendations), and 1868 intersections. Differences in relative importance between LTC and GAC emerged for stakeholders (staff, managers vs. caregivers, ethics committees), and for research stages (funding, facility recruitment vs. ethics, individual recruitment). Crucial themes according to specific stakeholders were collaboration for the research team; communication, trust, and human resources for managers; heterogeneity for patients and residents. A heatmap framework synthesizing vital stakeholders and themes per research stage was generated. CONCLUSIONS: We identified and quantified the interactions between stakeholders, stages, and themes to characterize heterogeneity in LTC and GAC research. Our framework may serve as a blueprint to co-construct and improve each stage of the research process.

The Association Between Somatic Symptom Disorders and Neurocognitive Disorders: A Systematic Review.

OBJECTIVE: Onset of neuropsychiatric symptoms in older adults may represent prodromal manifestations of neurodegenerative disorders. The association between the onset of somatic symptom and related disorders (SSRD) and the subsequent development of neurodegenerative disorders remains unclear. A critical review of studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia was performed. OBJECTIVE: To critically review studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia. METHODS: A systematic review of Web of Science Core databases was carried out from inception of databases up to May 2021 to identify observational studies pertaining to both SSRD and neurodegenerative disorders. Data was extracted and compiled regarding subjects enrolled, age at onset of the SSRD and at onset of the neurodegenerative disorders, and specific SSRD manifestations and underlying neuropathologies reported. RESULTS: Thirteen articles were included. Of the 123 identified subjects with SSRD at baseline, 34.1% developed a neurodegenerative disorder, with 80.9% of these being a Lewy body spectrum disorder. The interval between onset of SSRD manifestations and subsequent development of a neurodegenerative disorder was less than 3 years for half of the cases. Of the 1,494 subjects with a neurodegenerative disorder at baseline retrieved, SSRD manifestations were reported in 33.4% of Lewy body spectrum disorders cases. Onset of SSRD manifestations antedated or was concomitant to the diagnosis of the Lewy body spectrum disorder in 65.6% of cases. CONCLUSION: While limited, current evidence suggests a possible association between late-onset SSRD and the subsequent development of neurodegenerative disorders, notably Lewy body spectrum disorders.

Sleep apnea and the risk of dementia: A systematic review and meta-analysis.

Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic review and meta-analysis of cohort studies investigating the association between sleep apnea and specific aetiologies of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), vascular dementia (VaD), and frontotemporal dementia (FTD) was performed. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Eleven studies were included, comprising 1,333,424 patients. Patients with sleep apnea had an increased risk of developing any type of neurocognitive disorder (HR: 1.43 [95% CI 1.26-1.62]), Alzheimer's disease (HR: 1.28 [95% CI 1.16-1.41]), and Parkinson's disease (HR: 1.54 [95% CI 1.30-1.84]). No statistically significant association was found for vascular dementia. One study reported a two-fold increased risk for Lewy body dementia (HR: 2.06 [95% CI 1.45-2.91]). No studies investigated the risk for frontotemporal dementia and none of the studies reported results pertaining to biomarkers. Sleep apnea is associated with a significantly increased risk of dementia, particularly for Alzheimer's disease and Parkinson's disease, but not for vascular dementia. Future studies should look at the impact of sleep apnea on specific dementia biomarkers.

Models of Care in Geriatric Intensive Care-A Scoping Review on the Optimal Structure of Care for Critically Ill Older Adults Admitted in an ICU.

A growing proportion of critically ill patients admitted in ICUs are older adults. The need for improving care provided to older adults in critical care settings to optimize functional status and quality of life for survivors is acknowledged, but the optimal model of care remains unknown. We aimed to identify and describe reported models of care. DATA SOURCES: We conducted a scoping review on critically ill older adults hospitalized in the ICU. Medline (PubMed), Embase (OvidSP), Cumulative Index to Nursing and Allied Health Literature (Ebsco), and Web of Science (Clarivate) were searched from inception to May 5, 2020. STUDY SELECTION: We included original articles, published abstracts, review articles, editorials, and commentaries describing or discussing the implementation of geriatric-based models of care in critical care, step-down units, and trauma centers. The organization of care had to be described. Articles only discussing geriatric syndromes and specific interventions were not included. DATA EXTRACTION: Full texts of included studies were obtained. We collected publication and study characteristics, structures of care, human resources used, interventions done or proposed, results, and measured outcomes. Data abstraction was done by two investigators and reconciled, and disagreements were resolved by discussion. DATA SYNTHESIS: Our search identified 3,765 articles, and we found 19 reporting on the implementation of geriatric-based models of care in the setting of critical care. Four different models of care were identified: dedicated geriatric beds, geriatric assessment by a geriatrician, geriatric assessment without geriatrician, and a fourth model called "other approaches" including geriatric checklists, bundles of care, and incremental educational strategies. We were unable to assess the superiority of any model due to limited data. CONCLUSIONS: Multiple models have been reported in the literature with varying degrees of resource and labor intensity. More data are required on the impact of these models, their feasibility, and cost-effectiveness.

Appraising clinical applicability of studies: mapping and synthesis of current frameworks, and proposal of the FrACAS framework and VICORT checklist.

BACKGROUND: Not all research findings are translated to clinical practice. Reasons for lack of applicability are varied, and multiple frameworks and criteria exist to appraise the general applicability of epidemiological and clinical research. In this two-part study, we identify, map, and synthesize frameworks and criteria; we develop a framework to assist clinicians to appraise applicability specifically from a clinical perspective. METHODS: We conducted a literature search in PubMed and Embase to identify frameworks appraising applicability of study results. Conceptual thematic analysis was used to synthesize frameworks and criteria. We carried out a framework development process integrating contemporary debates in epidemiology, findings from the literature search and synthesis, iterative pilot-testing, and brainstorming and consensus discussions to propose a concise framework to appraise clinical applicability. RESULTS: Of the 4622 references retrieved, we identified 26 unique frameworks featuring 21 criteria. Frameworks and criteria varied by scope and level of aggregation of the evidence appraised, target user, and specific area of applicability (internal validity, clinical applicability, external validity, and system applicability). Our proposed Framework Appraising the Clinical Applicability of Studies (FrACAS) classifies studies in three domains (research, practice informing, and practice changing) by examining six criteria sequentially: Validity, Indication-informativeness, Clinical relevance, Originality, Risk-benefit comprehensiveness, and Transposability (VICORT checklist). CONCLUSIONS: Existing frameworks to applicability vary by scope, target user, and area of applicability. We introduce FrACAS to specifically assess applicability from a clinical perspective. Our framework can be used as a tool for the design, appraisal, and interpretation of epidemiological and clinical studies.

The state of frailty in research: A mapping review of its clinical applicability to practice.

Research on frailty has expanded in the last decade, but direct evidence supporting its implementation in clinical practice may be limited. This mapping review synthesizes the contexts-of-use and overall clinical applicability of recent pre-COVID frailty research. We sampled 476 articles from articles published on frailty in PubMed and EMBASE in 2017-2018, of which 150 articles were fully appraised for the contexts-of-use, definitions, and interventions. A clinical applicability framework was used to classify articles as practice-changing, practice-informing, or not practice-informing. Of the 476 sampled articles, 31% (n = 150) used frailty in functions that could inform a clinical indication: predictor or mediator (26%, n = 125), selection criterion (3%, n = 15), and effect modifier (2%, n = 10). Articles spanned all health disciplines, and cohort studies comprised 91% (n = 137) of studies and trials 9% (n = 13). Thirty-eight frailty definitions using varied cut-offs and a wide range of interventions were identified. Among all articles, 13% (n = 63) of articles were practice-informing, 2% (n = 11) potentially practice-changing, and 0.2% (n = 1) clearly practice-changing. Lack of well-defined intervention and identifiable effect (96%) or originality (83%) were predominant reasons reducing applicability. Only a minority of recent frailty research provides direct evidence of applicability to practice. Future research on frailty should focus on translating frailty, as a risk factor, into a clinical indication and address definition ambiguity.

Delirium and Inflammation in Older Adults Hospitalized for COVID-19: A Cohort Study.

PURPOSE: The occurrence and predictors of delirium in older adults hospitalized for coronavirus disease 2019 (COVID-19) have not been well described. Highlighting the association with inflammatory markers may be useful for identifying delirium. This study aimed to determine the prevalence and incidence of delirium and explore its association with the C-reactive protein (CRP). PATIENTS AND METHODS: This cohort study of adults aged 65 and older with a COVID-19 diagnosis took place at an academic healthcare institution between April and May 2020. COVID-19 was diagnosed by positive nasopharyngeal swab. Serum levels of CRP were collected as a marker of systemic inflammation. The primary outcome was the prevalence and incidence of delirium. Delirium was diagnosed primarily during a patient's stay in hospital based on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). To ensure that no delirium diagnosis was missed during hospital stay, clinical records were reviewed by clinicians with geriatric medicine training for retrospective diagnoses. RESULTS: A total of 127 patients aged 65 and older were hospitalized with a diagnosis of COVID-19. The median age was 82 years (IQR: 74-88), with 54 (43%) females. Overall, delirium was present in 62 (49%) patients: manifestations of delirium were present on the first day of hospitalization in 53 of these cases (86%), while 9 cases (14%) developed delirium during hospitalization. After controlling for age and sex, the mean CRP value over the first 3 days since arrival was associated with a higher risk of delirium (OR 1.35; 95% CI: 1.01-1.85) for every 50 mg/L increase. CONCLUSION: In this cohort of older adults hospitalized for COVID-19, delirium was highly prevalent. An early increase in CRP levels should raise suspicion about the occurrence of delirium and could improve its diagnosis.

Health Heterogeneity in Older Adults: Exploration in the Canadian Longitudinal Study on Aging.

BACKGROUND: A widely held dictum in aging research is that heterogeneity in health increases with age, but the basis for this claim has not been fully investigated. We examined heterogeneity at different ages across health characteristics to describe variation and trends; we investigated the comparative importance of between-age versus within-age heterogeneity. DESIGN: This was a cohort study. SETTING: Community-dwelling older adults. PARTICIPANTS: A total of 30,097 adults aged 45 to 86 years, from the Canadian Longitudinal Study on Aging, were included. MEASUREMENTS: Thirty-four health characteristics in eight domains (physical measures, vital signs, physiological measures, physical performance, function/disability, chronic conditions, frailty, laboratory values) were assessed cross-sectionally. We used regression models to examine heterogeneity in health characteristics (using absolute deviation) and domains (using effective variance) in relation to age. Comparison between between-age and within-age heterogeneity was quantified by estimating the age threshold at which the former exceeds the latter. RESULTS: Of the 34 health characteristics, 17 showed increased heterogeneity, 8 decreased, and 9 no association with age. The associations between heterogeneity and age increased generally but were nonlinear for most domains and nonmonotonic for some. We observed peak heterogeneity at approximately 70 years. Between-age heterogeneity, compared with within-age heterogeneity, was most important for forced expiratory volume in 1 second and grip strength but varied across characteristics. CONCLUSION: Overall health heterogeneity increases with age but does not uniformly increase across all variables and domains. Heterogeneity in aging reinforces the need for geriatric assessment and personalized care, depending on which health characteristics are assessed, their measurement properties, and their referent group. Our findings suggest further research to develop improved single-dimension and multidimensional instruments, as well as specific vital and laboratory reference ranges for older adults.

Potentially Inappropriate Medication Use in Older Adults in the Preoperative Period: A Retrospective Study of a Noncardiac Surgery Cohort.

BACKGROUND: Few studies have evaluated the prevalence of potentially inappropriate medications (PIMs) and its association with postoperative outcomes in a geriatric population in the preoperative setting. OBJECTIVES: The purpose of this study was to evaluate the prevalence of PIMs in an older elective surgery population and to explore associations between PIMs and postoperative length of stay (LOS) and emergency department (ED) visits in the 90 days post hospital discharge, depending on frailty status. METHODOLOGY: We performed a retrospective cohort study of older adults awaiting major elective noncardiac surgery and undergoing an evaluation in the preoperative clinic at a tertiary academic center between 2017 and 2018. We identified PIMs using MedSafer, a software tool built to improve the safety of prescribing. Frailty status was assessed using the 7-point Clinical Frailty Scale. We estimated the association between PIMs and postoperative LOS and ED visits in the 90 days post hospital discharge. RESULTS: The MedSafer software generated 394 recommendations on PIMs in 1619 medications for 252 patients. In total, 197 (78%) patients had at least one PIM. The cohort included 138 (51%) robust, 87 (32.2%) vulnerable and 45 (16.7%) frail patients. The association between PIMs and LOS was not significant for the robust and frail subgroups. For the vulnerable patients, every additional PIM increased LOS by 20% (incidence rate ratio 1.20; 95% confidence interval 0.90-1.44; p = 0.089) without reaching statistical significance. No association was found between PIMs and ED visits. CONCLUSION: PIMs identified by the MedSafer software were prevalent. Preoperative evaluation represents an opportunity to plan deprescribing of PIMs.