scholarly journals Prolonged anesthesia alters brain synaptic architecture

2019 ◽  
Author(s):  
Michael Wenzel ◽  
Alexander Leunig ◽  
Shuting Han ◽  
Darcy S. Peterka ◽  
Rafael Yuste

SUMMARYProlonged medically-induced coma (pMIC), a procedure performed in millions of patients worldwide, leads to cognitive impairment, yet the underlying brain mechanism remains unknown. No experimental studies of medically-induced coma (MIC) exceeding ~6 hours exist. For MIC of less than 6 hours, studies in developing rodents have documented transient changes of cortical synapse formation. However, in adulthood, cortical synapses are thought to become stabilized. Here, we establish pMIC (up to 24 hrs) in adolescent and mature mice, and combine repeated behavioral object recognition assessments with longitudinal two-photon imaging of cortical synapses. We find that pMIC affects cognitive function, and is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the post-anesthetic period is dominated by synaptic loss. These results carry profound implications for intensive medical care, as they point out at significant structural side effects of pMIC on cortical brain synaptic architecture across age levels.

2021 ◽  
Vol 118 (7) ◽  
pp. e2023676118
Author(s):  
Michael Wenzel ◽  
Alexander Leunig ◽  
Shuting Han ◽  
Darcy S. Peterka ◽  
Rafael Yuste

Prolonged medically induced coma (pMIC) is carried out routinely in intensive care medicine. pMIC leads to cognitive impairment, yet the underlying neuromorphological correlates are still unknown, as no direct studies of MIC exceeding ∼6 h on neural circuits exist. Here, we establish pMIC (up to 24 h) in adolescent and mature mice, and combine longitudinal two-photon imaging of cortical synapses with repeated behavioral object recognition assessments. We find that pMIC affects object recognition, and that it is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the postanesthetic period is dominated by synaptic loss. Our results demonstrate major side effects of prolonged anesthesia on neural circuit structure.


2005 ◽  
Vol 33 (5) ◽  
pp. 1037-1040 ◽  
Author(s):  
M.W.J. Strachan

Data from experimental studies in animals and from epidemiological studies in humans suggest a link between insulin and cognitive performance. Do these results translate into clinical and therapeutic benefit for people with cognitive impairment? Insulin injected peripherally can readily cross the blood–brain barrier. Intravenous insulin can improve aspects of cognitive function in healthy adults and in individuals with Alzheimer's dementia. Moreover, intravenous insulin increases concentrations of a long form of β-amyloid protein, Aβ42. One potential confounding factor with these data, however, is the need for co-administration of glucose with the insulin to maintain euglycaemia as glucose itself can facilitate memory function. Administration of insulin via the intranasal route is scientifically (and therapeutically) more attractive because the insulin goes directly to the cerebrospinal fluid, with minimal systemic absorption; this obviates the need for a glucose infusion. Intranasal insulin may improve some aspects of memory in healthy individuals, but has yet to be studied in people with cognitive impairment. TZDs (thiazolidinediones) reduce peripheral insulin concentrations by enhancing insulin sensitivity. In adults with Type II (non-insulin-dependent) diabetes, TZD therapy improves memory function, but so does sulphonylurea therapy (which elevates peripheral insulin concentrations). Improved memory is linked to lower blood glucose concentrations, rather than altered insulin levels. However, major trials are currently under way examining the impact of TZDs in people with dementia.


2020 ◽  
Vol 32 (9) ◽  
pp. 1165-1177 ◽  
Author(s):  
Duy Do ◽  
Jason Schnittker

Objectives: Many medications have cognitive impairment, memory loss, amnesia, or dementia as side effects (“cognitive side effects” hereafter), but little is known about trends in the prevalence of these medications or their implications for population-level cognitive impairment. Method: We use data from the National Health and Nutrition Examination Survey (1999–2016) to describe trends in the use of medications with cognitive side effects among adults aged 60+ ( N = 16,937) and their implications for cognitive functioning (measured using word learning and recall, animal fluency, and digit symbol substitution assessments). Results: Between 1999 to 2000 and 2015 to 2016, the prevalence of older adults taking one, two, and at least three medications with cognitive side effects increased by 10.2%, 57.3%, and 298.7%, respectively. Compared to non-users, respondents who simultaneously used three or more medications with cognitive side effects scored 0.22 to 0.27 standard deviations lower in word learning and recall ( p = .02), digit symbol substitution ( p < .01), and the average standardized score of the three assessments ( p < .001). Limitation: Dosage of medications associated with cognitive side effects was not measured. Discussion: Concurrent use of medications with cognitive side effects among older adults has increased dramatically over the past two decades. The use of such medications is associated with cognitive impairment and may explain for disparities in cognitive function across subgroups. These findings highlight the need for cognitive screenings among patients who consume medications with cognitive side effects. They also highlight the synergic effects of polypharmacy and potential drug-drug interactions that result in cognitive deficits.


BMJ Open ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. e024429 ◽  
Author(s):  
Niamh A Merriman ◽  
Eithne Sexton ◽  
Grainne McCabe ◽  
Mary E Walsh ◽  
Daniela Rohde ◽  
...  

ObjectiveCognitive impairment is a pervasive outcome of stroke, reported in over half of patients 6 months post-stroke and is associated with increased disability and a poorer quality of life. Despite the prevalence of post-stroke cognitive impairment, the efficacy of existing psychological interventions for the rehabilitation of cognitive impairment following stroke has yet to be established. The aim of this study is to identify psychological interventions from non-randomised studies that intended to improve post-stroke cognitive function and establish their efficacy.DesignSystematic review and meta-analysis of non-randomised studies of psychological interventions addressing post-stroke cognitive impairment.Data sourcesElectronic searches were performed in the Pubmed, EMBASE and PsycINFO databases, the search dating from inception to February 2017.Eligibility criteriaAll non-randomised controlled studies and quasi-randomised controlled trials examining psychological interventions to improve cognitive function following stroke were included, such as feasibility studies, pilot studies, experimental studies, and quasi-experimental studies. The primary outcome was cognitive function. The prespecified secondary outcomes were functional abilities in daily life and quality of life.MethodsThe current meta-analyses combined the findings of seven controlled studies, examining the efficacy of psychological interventions compared with treatment-as-usual controls or active controls, and 13 one-group pre–post studies.ResultsResults indicated an overall small effect on cognition across the controlled studies (Hedges' g=0.38, 95% CI=0.06 to 0.7) and a moderate effect on cognition across the one-group pre–post studies (Hedges' g=0.51, 95% CI=0.3 to 0.73). Specific cognitive domains, such as memory and attention also demonstrated a benefit of psychological interventions.ConclusionsThis review provides support for the potential of psychological interventions to improve overall cognitive function post-stroke. Limitations of the study, in terms of risk of bias and quality of included studies, and future research directions are explored.PROSPERO registration numberCRD42017069714.


2016 ◽  
Vol 64 (2) ◽  

Strategies to improve cognitive aging are highly needed. Among those, promotion of exercise and physical activity appears as one of the most attractive and beneficial intervention. Indeed, results from basic and clinical studies suggest that exercise and physical activity have positive effects on cognition in older persons without cognitive impairment, as well as in those with dementia. Despite inconsistent results, aerobic exercise appears to have the strongest potential to enhance cognition. However, even limited periods of walking (45 minutes, three times a week, over a 6-month period) have also been shown to enhance cognition, particularly executive functions. Changing long-term lifestyle habits in these older persons remains a critical challenge and attractive programs susceptible to gain adherence are needed to succeed in achieving improved cognitive aging.


2020 ◽  
Vol 17 (6) ◽  
pp. 556-565
Author(s):  
Yujie Guo ◽  
Pengfei Li ◽  
Xiaojun Ma ◽  
Xiaochen Huang ◽  
Zhuoheng Liu ◽  
...  

Background: The present study was designed to examine the association of circulating cholesterol with cognitive function in non-demented community aging adults. Methods: This was a cross-sectional study including 1754 Chinese adults aged 55-80 years. The association between serum cholesterol levels and cognitive function was examined. Participants were categorized into four groups according to the quartile of circulating TC (total cholesterol), High Density Lipoprotein Cholesterol (HDL-c), Low Density Lipoprotein Cholesterol (LDL-c) levels and HDLc/ LDL-c ratio. The difference in cognitive performance among the groups was compared. Logistic regression model was used to determine the association of circulating cholesterol level with the risk of Mild Cognitive Impairment (MCI). Results: Mild increase of serum LDL-c level correlated with better visual and executive, language, memory and delayed recall abilities. Higher circulating TC and HDL-c levels were found to be associated with poorer cognitive function, especially in aging female subjects. Higher circulating TC, HDL-c and HDL/LDL ratio indicated an increased risk of MCI, especially in female subjects. Conclusion: Slight increase in circulating LDL-c level might benefit cognitive function in aging adults. However, higher circulating TC and HDL-c levels might indicate a decline of cognitive function, especially in aging female subjects.


2020 ◽  
Vol 16 (14) ◽  
pp. 1309-1315
Author(s):  
Peilin An ◽  
Xuan Zhou ◽  
Yue Du ◽  
Jiangang Zhao ◽  
Aili Song ◽  
...  

Background: Inflammation plays a significant role in the pathophysiology of cognitive impairment in previous studies. Neutrophil-lymphocyte ratio (NLR) is a reliable measure of systemic inflammation. Objective: The aim of this study was to investigate the association between NLR and mild cognitive impairment (MCI), and further to explore the diagnostic potential of the inflammatory markers NLR for the diagnosis of MCI in elderly Chinese individuals. Methods: 186 MCI subjects and 153 subjects with normal cognitive function were evaluated consecutively in this study. Neutrophil (NEUT) count and Lymphocyte (LYM) count were measured in fasting blood samples. The NLR was calculated by dividing the absolute NEUT count by the absolute LYM count. Multivariable logistic regression was used to evaluate the potential association between NLR and MCI. NLR for predicting MCI was analyzed using Receiver Operating Characteristic (ROC) curve analysis. Results: The NLR of MCI group was significantly higher than that of subjects with normal cognitive function (2.39 ± 0.55 vs. 1.94 ± 0.51, P < 0.001). Logistic regression analysis showed that higher NLR was an independent risk factor for MCI (OR: 4.549, 95% CI: 2.623-7.889, P < 0.001). ROC analysis suggested that the optimum NLR cut-off point for MCI was 2.07 with 73.66% sensitivity, 69.28% specificity, 74.48% Positive Predictive Values (PPV) and 68.36% negative predictive values (NPV). Subjects with NLR ≥ 2.07 showed higher risk relative to NLR < 2.07 (OR: 5.933, 95% CI: 3.467-10.155, P < 0.001). Conclusion: The elevated NLR is significantly associated with increased risk of MCI. In particular, NLR level higher than the threshold of 2.07 was significantly associated with the probability of MCI.


The prevalence of cognitive impairment caused by neurodegenerative diseases and other neurologic disorders associated with aging is expected to rise dramatically between now and year 2050, when the population of Americans aged 65 or older will nearly double. Cognitive impairment also commonly occurs in other neurologic conditions, as well as in non-neurologic medical disorders (and their treatments), idiopathic psychiatric illnesses, and adult neurodevelopmental disorders. Cognitive impairment can thus infiltrate all aspects of healthcare, making it necessary for clinicians and clinical researchers to have an integrated knowledge of the spectrum of adult cognitive disorders. The Oxford Handbook of Adult Cognitive Disorders is meant to serve as an up-to-date, scholarly, and comprehensive volume covering most diseases, conditions, and injuries resulting in impairments in cognitive function in adults. Topics covered include normal cognitive and brain aging, the impact of medical disorders (e.g., cardiovascular, liver, pulmonary) and psychiatric illnesses (e.g., depression and bipolar disorder) on cognitive function, adult neurodevelopmental disorders (e.g., Down Syndrome, Attention Deficit/Hyperactivity Disorder), as well as the various neurological conditions (e.g., Alzheimer’s disease, chronic traumatic encephalopathy, concussion). A section of the Handbook is also dedicated to unique perspectives and special considerations for the clinicians and clinical researchers, covering topics such as cognitive reserve, genetics, diversity, and neuroethics. The target audience of this Handbook includes: (1) clinicians, particularly psychologists, neuropsychologists, neurologists (including behavioral and cognitive neurologists), geriatricians, and psychiatrists (including neuropsychiatrists), who provide clinical care and management for adults with a diverse range of cognitive disorders; (2) clinical researchers who investigate cognitive outcomes and functioning in adult populations; and (3) graduate level students and post-doctoral trainees studying psychology, clinical neuroscience, and various medical specialties.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alexandre Chan ◽  
Angie Yeo ◽  
Maung Shwe ◽  
Chia Jie Tan ◽  
Koon Mian Foo ◽  
...  

Abstract Strong evidence suggests that genetic variations in DNA methyltransferases (DNMTs) may alter the downstream expression and DNA methylation patterns of neuronal genes and influence cognition. This study investigates the association between a DNMT1 polymorphism, rs2162560, and chemotherapy-associated cognitive impairment (CACI) in a cohort of breast cancer patients. This is a prospective, longitudinal cohort study. From 2011 to 2017, 351 early-stage breast cancer patients receiving chemotherapy were assessed at baseline, the midpoint, and the end of chemotherapy. DNA was extracted from whole blood, and genotyping was performed using Sanger sequencing. Patients’ self-perceived cognitive function and cognitive performance were assessed at three different time points using FACT-Cog (v.3) and a neuropsychological battery, respectively. The association between DNMT1 rs2162560 and cognitive function was evaluated using logistic regression analyses. Overall, 33.3% of the patients reported impairment relative to baseline in one or more cognitive domains. Cognitive impairment was observed in various objective cognitive domains, with incidences ranging from 7.2% to 36.9%. The DNMT1 rs2162560 A allele was observed in 21.8% of patients and this was associated with lower odds of self-reported cognitive decline in the concentration (OR = 0.45, 95% CI: 0.25–0.82, P = 0.01) and functional interference (OR = 0.48, 95% CI: 0.24–0.95, P = 0.03) domains. No significant association was observed between DNMT1 rs2162560 and objective cognitive impairment. This is the first study to show a significant association between the DNMT1 rs2162560 polymorphism and CACI. Our data suggest that epigenetic processes could contribute to CACI, and further studies are needed to validate these findings.


Author(s):  
Tran Dai Tri Han ◽  
Keiko Nakamura ◽  
Kaoruko Seino ◽  
Vo Nu Hong Duc ◽  
Thang Van Vo

This study examined the prevalence of cognitive impairment among older adults in central Vietnam and the roles of communication (with or without communication devices) in the association between cognitive impairment and hearing loss. This cross-sectional study was performed on 725 randomly selected community-dwelling older adults aged ≥60 years from Thua Thien Hue province, Vietnam. Participants attended a face-to-face survey. Sociodemographic characteristics, social interaction with or without communication devices, health status and cognitive function using the Mini-Mental State Examination were reported. Ordinal logistic regression analysis was performed to quantify the association between hearing loss and cognitive function by frequency of communication with and without devices. Mild and severe cognitive impairment had prevalence rates of 23.6% and 19.3%, respectively. Cognitive impairment was more prevalent among older adults with hearing-loss, vision loss and difficulties with instrumental activities of daily living (IADL). The association between hearing loss and cognitive impairment was not significant when older adults had frequent communication with others using devices. This study presented the relatively high prevalence of cognitive impairment in community-dwelling older adults in Vietnam. Frequent communication using devices attenuated the association between hearing loss and cognitive impairment.


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