Biological Mechanisms of Cognitive and Physical Impairments after Critical Care. Rethinking the Inflammatory Model?
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SUBMITTER: Parker AM
PROVIDER: S-EPMC7958509 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesImproved ability to predict impairments after critical illness could guide clinical decision-making, inform trial enrollment, and facilitate comprehensive patient recovery. A systematic review of the literature was conducted to investigate whether physical, cognitive, and mental health impairments could be predicted in adult survivors of critical illness.Data sourcesA systematic search of PubMed and the Cochrane Library (Prospective Register of Systematic Reviews ID: CRD42018117255) was undertaken on December 8, 2018, and the final searches updated on January 20, 2019.Study selectionFour independent reviewers assessed titles and abstracts against study eligibility criteria. Studies were eligible if a prediction model was developed, validated, or updated for impairments after critical illness in adult patients. Discrepancies were resolved by consensus or an independent adjudicator.Data extractionData on study characteristics, timing of outcome measurement, candidate predictors, and analytic strategies used were extracted. Risk of bias was assessed using the Prediction model Risk Of Bias Assessment Tool.Data synthesisOf 8,549 screened studies, three studies met inclusion. All three studies focused on the development of a prediction model to predict (1) a mental health composite outcome at 3 months post discharge, (2) return-to-pre-ICU functioning and residence at 6 months post discharge, and (3) physical function 2 months post discharge. Only one model had been externally validated. All studies had a high risk of bias, primarily due to the sample size, and statistical methods used to develop and select the predictors for the prediction published model.ConclusionsWe only found three studies that developed a prediction model of any post-ICU impairment. There are several opportunities for improvement for future prediction model development, including the use of standardized outcomes and time horizons, and improved study design and statistical methodology.
| S-EPMC7673641 | biostudies-literature
Project description:BackgroundMany older adults receive caregiving; however, less is known about how a change in a care recipient's functional activity limitations [instrumental activities of daily living (IADL) and basic activities of daily living (ADL)] as well as their cognitive impairment influence the amount of caregiving received.MethodsUsing the Health and Retirement Study (2002-2014) we identified community-dwelling respondents with Alzheimer disease and related dementias (ADRD; n=674), cognitive impairment no dementia (CIND; n=530), and no cognitive impairment (n=6126). We estimated a series of two-part regression models to identify the association between care recipients' level of cognitive impairment, change in total number of IADL/ADL limitations and amount of caregiving received.ResultsPersons with ADRD received 235.8 (SD=265.6) monthly hours of care compared with 26.0 (SD=92.6) and 6.0 (SD=40.7) for persons with CIND and no cognitive impairment, respectively. An increase in one IADL/ADL limitation resulted in persons with ADRD and CIND receiving 4.90 (95% confidence interval: 3.40-6.39) and 1.43 (95% confidence interval: 0.17-2.69) more hours of caregiving than persons with no cognitive impairment. Increases in total IADL/ADL limitations were associated with persons with ADRD, but not CIND, receiving more days of caregiving and having more caregivers than persons with no cognitive impairment.ConclusionsCompared with persons with no cognitive impairment, increases in IADL/ADL limitations disproportionally increases the caregiving received for persons with ADRD. Policies and programs must pay attention to functional impairments among those living with ADRD.
| S-EPMC7289673 | biostudies-literature
Project description:IntroductionWe describe findings from a large study that provide empirical support for the emerging construct of cognitive frailty and put forth a theoretical framework that may advance the future study of complex aging conditions. While cognitive impairment and physical frailty have long been studied as separate constructs, recent studies suggest they share common etiologies. We aimed to create a population predictive model to gain an understanding of the underlying biological mechanisms for the relationship between physical frailty and cognitive impairment.MethodsData were obtained from the longitudinal "Invecchaiare in Chianti" (Aging in Chianti, InCHIANTI Study) with a representative sample (n = 1453) of older adults from two small towns in Tuscany, Italy. Our previous work informed the candidate 132 single nucleotide polymorphisms (SNPs) and 155 protein biomarkers we tested in association with clinical outcomes using a tree boosting, machine learning (ML) technique for supervised learning analysis.ResultsWe developed two highly accurate predictive models, with a Model I area under the curve (AUC) of 0.88 (95% confidence interval [CI] 0.83-0.90) and a Model II AUC of 0.86 (95% CI 0.80-0.90). These models indicate cognitive frailty is driven by dysregulation across multiple cellular processes including genetic alterations, nutrient and lipid metabolism, and elevated levels of circulating pro-inflammatory proteins.DiscussionWhile our results establish a foundation for understanding the underlying biological mechanisms for the relationship between cognitive decline and physical frailty, further examination of the molecular pathways associated with our predictive biomarkers is warranted. Our framework is in alignment with other proposed biological underpinnings of Alzheimer's disease such as genetic alterations, immune system dysfunction, and neuroinflammation.
| S-EPMC7362211 | biostudies-literature
Project description:To evaluate process metrics and outcomes after implementation of the "Rethinking Critical Care" ICU care bundle in a community setting.Retrospective interrupted time-series analysis.Three hospitals in the Kaiser Permanente Northern California integrated healthcare delivery system.ICU patients admitted between January 1, 2009, and August 30, 2013.Implementation of the Rethinking Critical Care ICU care bundle which is designed to reduce potentially preventable complications by focusing on the management of delirium, sedation, mechanical ventilation, mobility, ambulation, and coordinated care. Rethinking Critical Care implementation occurred in a staggered fashion between October 2011 and November 2012.We measured implementation metrics based on electronic medical record data and evaluated the impact of implementation on mortality with multivariable regression models for 24,886 first ICU episodes in 19,872 patients. After implementation, some process metrics (e.g., ventilation start and stop times) were achieved at high rates, whereas others (e.g., ambulation distance), available late in the study period, showed steep increases in compliance. Unadjusted mortality decreased from 12.3% to 10.9% (p < 0.01) before and after implementation, respectively. The adjusted odds ratio for hospital mortality after implementation was 0.85 (95% CI, 0.73-0.99) and for 30-day mortality was 0.88 (95% CI, 0.80-0.97) compared with before implementation. However, the mortality rate trends were not significantly different before and after Rethinking Critical Care implementation. The mean duration of mechanical ventilation and hospital stay also did not demonstrate incrementally greater declines after implementation.Rethinking Critical Care implementation was associated with changes in practice and a 12-15% reduction in the odds of short-term mortality. However, these findings may represent an evaluation of changes in practices and outcomes still in the midimplementation phase and cannot be directly attributed to the elements of bundle implementation.
| S-EPMC4764399 | biostudies-literature
Project description:IntroductionWomen are more vulnerable to stress-related disorders than men, which is counterintuitive as female sex hormones, especially estrogen, have been shown to be protective against stress disorders.MethodsIn this study, we investigated whether two different models of stress act differently on ovariectomized (OVX) rats and the impact of estrogen on physical or psychological stress-induced impairments in cognitive-behaviors. Adult female Wistar rats at 21-22 weeks of age were utilized for this investigation. Sham and OVX rats were subjected to physical and psychological stress for 1 hr/day for 7 days, and cognitive performance was assessed using morris water maze (MWM) and passive avoidance (PA) tests. The open field and elevated plus maze tests (EPM) evaluated exploratory and anxiety-like behaviors.ResultsIn sham and OVX rats, both physical and psychological stressors were associated with an increase in EPM-determined anxiety-like behavior. OVX rats exhibited decreased explorative behavior in comparison with nonstressed sham rats (p < .05). Both physical stress and psychological stress resulted in disrupted spatial cognition as assayed in the MWM (p < .05) and impaired learning and memory as determined by the PA test when the OVX and sham groups were compared with the nonstressed sham group. Estrogen increased explorative behavior, learning and memory (p < .05), and decreased anxiety-like behavior compared with vehicle in OVX rats exposed to either type of stressor.ConclusionsWhen taken together, estrogen and both stressors had opposite effects on memory, anxiety, and PA performance in a rat model of menopause, which has important implications for potential protective effects of estrogen in postmenopausal women exposed to chronic stress.
| S-EPMC8119870 | biostudies-literature
Project description:Background and Objectives:The objective of the study was to understand how sensory impairments, alone or in combination with cognitive impairment (CI), relate to long-term care (LTC) admissions. Research Design and Methods:This retrospective cohort study used existing information from two interRAI assessments; the Resident Assessment Instrument for Home Care (RAI-HC) and the Minimum Data Set 2.0 (MDS 2.0), which were linked at the individual level for 371,696 unique individuals aged 65+ years. The exposure variables of interest included hearing impairment (HI), vision impairment (VI) and dual sensory impairment (DSI) ascertained at participants' most recent RAI-HC assessment. The main outcome was admission to LTC. Survival analysis, using Cox proportional hazards regression models and Kaplan-Meier curves, was used to identify risk factors associated with LTC admissions. Observations were censored if they remained in home care, died or were discharged somewhere other than to LTC. Results:In this sample, 12.7% of clients were admitted to LTC, with a mean time to admission of 49.6 months (SE = 0.20). The main risk factor for LTC admission was a diagnosis of Alzheimer's dementia (HR = 1.87; CI: 1.83, 1.90). A significant interaction between HI and CI was found, whereby individuals with HI but no CI had a slightly faster time to admission (40.5 months; HR = 1.14) versus clients with both HI and CI (44.9 months; HR = 2.11). Discussion and Implications:Although CI increases the risk of LTC admission, HI is also important, making it is imperative to continue to screen for sensory issues among older home care clients.
| S-EPMC6938463 | biostudies-literature
Project description:ObjectiveSurvivors of critical illness may experience short- and long-term physical function impairments. This review aimed to identify the risk factors for physical function impairments from the current literature.Data sourcesA systematic search of the PubMed, Embase, Web of Science, and Cochrane Library databases following the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews guideline was performed.Study selectionThe risk factors reported in all human studies reporting physical function impairments in children admitted to the pediatric intensive care unit (PICU) were reviewed and categorized. Two investigators independently screened, evaluated, and selected studies for inclusion. Data from eligible studies were extracted by one investigator, and another investigator reviewed and verified the data. A systematic narrative approach was employed to review and summarize the data.ResultsA total of 264 studies were found to be eligible, with 19 studies meeting the inclusion criteria. Children admitted to the PICU experienced physical function impairments during their stay, which can last for years. The studies varied primarily in the measurement timing and tools used. The most frequently reported risk factors for physical function impairments were age, race or ethnicity, a pre-admission chronic condition, sex, disease severity, duration or the presence of mechanical ventilation, and admission diagnosis.ConclusionsPhysical function impairments may be persistent in PICU survivors. To prevent these impairments in critically ill patients, pediatricians should pay attention to modifiable risk factors, such as the duration of mechanical ventilation. Future studies need to promote a combination of standardized measures for the detection and prevention of physical function impairments.
| S-EPMC9249083 | biostudies-literature
Project description:This systematic review analyzes current data on effects of exercise interventions and physical activity behavior on objective and subjective cancer related cognitive impairments (CRCI). Out of the 19 studies which met all inclusion criteria, five RCTs investigated rodents, whereas the other 14 trials explored humans and these included six RCTs, one controlled trial, two prospective noncontrolled trials, one case series, one observational study, and three cross-sectional studies. The results from animal models revealed positive effects of exercise during and after chemotherapy or radiation on structural alterations of the central nervous system, physiological as well as neuropsychological outcomes. The overall study quality in patient studies was poor. The current data on intervention studies showed preliminary positive effects of Asian-influenced movement programs (e.g., Yoga) with benefits on self-perceived cognitive functions as well as a reduction of chronic inflammation for breast cancer patients in the aftercare. Exercise potentially contributes to the prevention and rehabilitation of CRCI. Additional RCTs with standardized neuropsychological assessments and controlling for potential confounders are needed to confirm and expand preliminary findings.
| S-EPMC4842032 | biostudies-other
Project description:Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s) and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD) patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.
| S-EPMC4125179 | biostudies-literature
Project description:Posttraumatic stress disorder (PTSD) has been linked to increased prevalence and incidence of cognitive and physical impairment. When comorbid, these conditions may be associated with poor long-term outcomes. We examined associations between chronic PTSD and symptom domains with cognitive and physical functioning in World Trade Center (WTC) responders nearly 20 years after the September 11, 2001, terrorist attacks. Participants included a cross-sectional sample of 4,815 responders who attended a monitoring program in 2015-2018. Montreal Cognitive Assessment scores less than 23 indicated cognitive impairment (CogI); Short Physical Performance Battery scores 9 or lower on a hand-grip test indicated physical impairment (PhysI). Comorbid cognitive/physical impairment (Cog/PhysI) was defined as having cognitive impairment with at least one objective PhysI indicator. Clinical chart review provided PTSD diagnoses; symptom domains were assessed using the PTSD Checklist. Participants were on average 53.05 years (SD = 8.01); 13.44% had PTSD, 7.8% had CogI, 24.8% had PhysI, and 5.92% had comorbid Cog/PhysI. Multivariable-adjusted multinomial logistic regression demonstrated that Responders with PTSD have more than three times the risk of Cog/PhysI (adjusted RR = 3.29, 95% CI 2.44- 4.44). Domain-specific analyses revealed that emotional numbing symptoms predicted an increased risk of PhysI (adjusted RR = 1.57, 95% CI 1.08-2.28), whereas reexperiencing symptoms were associated with comorbid Cog/PhysI (adjusted RR = 3.96, 95% CI, 2.33-6.74). These results suggest that responders with chronic PTSD may have increased risk of deficits beyond age-expected impairment characterized by the emergence of comorbid Cog/PhysI at midlife.
| S-EPMC8137717 | biostudies-literature