Dysfunction In Elderly Patients Research Articles

The value of intraoperative cerebral oxygen saturation in predicting postoperative neurocognitive dysfunction in elderly patients with mild cognitive impairment

Objective: To evaluate the value of intraoperative cerebral oxygen saturation in predicting postoperative neurocognitive dysfunction (PND) in elderly patients with mild cognitive impairment. Methods: A total of 210 cases of lumbar decompression, bone grafting and fusion surgery under general anesthesia were collected in the Third Central Hospital of Tianjin from June, 2019 to January, 2020, either sex, aged 65-75 year, BMI 19.5-32.5 kg/m(2), ASA physical status Ⅱ or Ⅲ, preoperative comorbidities with mild cognitive impairment. MoCA and MMSE were used to evaluate the cognitive function of patients 1 day before the operation, 7 days and 3 monthes after operation. PND group (n=38) and non-PND group (n=172) were selected according to postoperative MMSE and MoCA scale scores and the diagnostic criteria of PND. Heart rate (HR) , mean arterial pressure (MAP), pulse oxygen saturation (SpO(2)), bispectral index (BIS), cerebral tissue oxygen saturation (SctO(2), average left and right brain SctO(2) were recorded) were recorded pre-anesthetic (T(0)), ten minutes of anesthesia(T(1)), twenty minutes of anesthesia (T(2)), thirty minutes into the operation (T(3)), one hour into the operation (T(4)), end of the surgery (T(5)), and leave the PACU (T(6)). SctO(2) at time point T(0) was the base value of SctO(2), and the maximum percentage drop in SctO(2) from the base value was calculated (SctO(2max)%). Results: The incidence of PND was 18% (38/210) in 210 elderly patients undergoing surgery. The age of PND group and non-PND group was (71.0±2.1) and (67.8±2.0) years old, and the PACU time was (57±5) and (46±8) min, respectively. Compared with the non-PND group, the age of the PND group was higher (t=2.600, P<0.05) and the PACU time was longer (t=3.039, P<0.05). At the time points T(3), T(4), T(5) and T(6), SctO(2) in the PND group was (62±10) %, (60±11) %, (64±12) % and (66±10)%, respectively, lower than that in the non-PND group (67±60) %, (68±6) %, (69±5) % and (70±7)%, respectively, and the difference was statistically significant (t=3.369, 4.906, 3.787, 2.516, all P<0.05).The MoCA and MMSE scores of the PND group were (22.9±1.2) and (24.1±1.2) points, respectively, 1 day before surgery; and the MoCA and MMSE scores of the PND group were reduced to (20.8±1.2) and (21.3±0.7) points, respectively, 7 days after surgery, with statistically significant differences (t=3.523, 5.675, all P<0.05). MoCA and MMSE scores 7 days after surgery in the non-PND group were (22.4±1.3) and (23.1±1.6) points, respectively. Compared with the non-PND group, MoCA and MMSE scores 7 days after surgery in the PND group were reduced (t=2.630, 3.108, all P<0.05). The critical value of intraoperative SctO(2max)% was 13.74%, the area under the curve of PND was predicted to be 0.907 (95%CI: 0.819-0.995), sensitivity and specificity were 88.9% and 88.5%, respectively. Conclusion: SctO(2max)%>13.74% can be used as an indicator to predict PND occurrence in elderly patients with mild cognitive impairment during lumbar surgery.

The correlation between tissue oxygen saturation and postoperative cognitive dysfunction in elderly patients with one lung ventilation

Objective: To investigate the correlation between tissue oxygen saturation during one lung ventilation and postoperative neuro cognitive dysfunction (PND) in elderly patients in thoracic surgery. Methods: One hundred and twenty-eight elderly patients who underwent selective lobectomy from August 2017 to September 2018 in the Forth Hospital of Hebei Medical University were enrolled. The patients were divided into PND group (n=34) and non-PND group (n=94) according to whether PND occurred 3 days after surgery. Tissue oxygenation was monitored at bilateral forebrain, brachioradialis muscle and quadriceps. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) at baseline and the third day after the operation. Postoperative cognitive dysfunction was diagnosed if postoperative MoCA decreased at least 2 scores compared with preoperative baseline value. Outcomes included the incidence of PND, the incidence of tissue oxygen desaturation during one lung ventilation, postoperative complications within 30 days and length of postoperative in-hospital stay. Logistic regression was used to screen independent risk factors of PND. Results: The incidence of postoperative cognitive dysfunction was 26.6% (34/128). The two groups had no significant difference in the incidence of non-neurogenic complications (new occurred arrhythmia, pulmonary infection, pulmonary embolism, acute renal insufficiency, sepsis, deep vein thrombosis, all P>0.05). However, the length of postoperative in-hospital stay of PND group was 7.0 (6.0, 8.5) d, which was longer than that of non-PND group [6.0 (5.0, 8.0) d]. There was significant difference (U=2.394, P=0.017) . There was no correlation between the two groups within the minimum of SmtO(2) in upper limbs (OR=0.988, 95%CI: 0.954-1.024, P=0.519) and the range of desaturation (OR=1.010, 95%CI: 0.979-1.042, P=0.514) , as well as the minimum of SmtO(2) in legs (OR=0.996, 95%CI: 0.961-1.032, P=0.832) and the range of desaturation (OR=0.997, 95%CI: 0.971-1.025, P=0.851) . Multivariate logistic regression analysis showed that the high ASA grade (OR=2.617, 95%CI: 1.112-6.157, P=0.029) and the minimum of cerebral oxygen saturation during one lung ventilation (OR=0.931, 95%CI: 0.880-0.986, P=0.014) were independent risk factors of PND. There was no statistical correlation between muscle oxygen saturation and PND. Conclusion: Cerebral desaturation during one lung ventilation increased the risk of PND in elderly patients, while the muscle desaturation has no statistical correlation with PND.

Correlation Between Plasma CircRNA-089763 and Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Non-cardiac Surgery.

In our previous experiment, we found that there were abnormal levels of circRNA-089763 in the plasma exosomes of patients with postoperative cognitive dysfunction (POCD) after cardiac surgery. Therefore, the aim of this study was to further investigate the relationship between plasma circRNA-089763 level and POCD in elderly patients after non-cardiac surgery. A prospective cohort study was conducted to select elderly patients undergoing elective non-cardiac surgery. A total of 72 patients were enrolled in this study, and cognitive functions were assessed 1 day before and 3 days after surgery by a series of neuropsychological measurements. Next, patients were divided into POCD and non-POCD (NPOCD) groups according to the Z score method. Blood was collected the day before and 3 days after surgery, and the plasma circRNA-089763 level was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the difference and correlation in plasma circRNA-089763 levels between the POCD and NPOCD groups were analyzed. On the third day after surgery, the incidence of POCD was 30.56%. The relative level of circRNA-089763 in the POCD group was 2.41 times higher than that in the NPOCD group (t = 4.711, p < 0.001), patients in POCD group had higher age (t = 5.971, p < 0.001), higher American Society of Anesthesiologists classification (χ2 = 14.726, p < 0.001), less years of education (t = 2.449, p = 0.017), more intraoperative blood loss (t = 3.196, p = 0.002), and higher visual analog scale (VAS) scores (t = 10.45, p < 0.001). The binary logistic regression analysis showed that the circRNA-089763 level, age, and intraoperative blood loss were independently associated with POCD (OR: 2.75, 95% CI: 1.261–5.999, p = 0.011; OR: 1.32, 95% CI: 1.114–1.565, p = 0.001; OR: 1.017, 95% CI: 1.004–1.03, p = 0.011). These results demonstrated that the circRNA-089763 plasma level was related to POCD after non-cardiac surgery in elderly patients.

Social Cognitive Dysfunction in Elderly Patients After Anesthesia and Surgery.

Extensive studies have revealed that cognitive processing was impaired after anesthesia and surgery, particularly for the elderly patients. However, most of the existing studies focused on the general cognitive deficits (e.g., delayed neuro-cognitive recovery and POCD). Although diagnosis of social abilities has been used in various clinical fields, few studies have investigated the potential deficit on social cognition after anesthesia and surgery. The current study examined whether there was any social cognitive dysfunction after anesthesia and surgery. We achieved this by taking biological motion (BM) as the stimuli of interest, the perception of which has been taken as the hallmark of social cognition. The elderly patients (aged ≥ 60 years) were required to judge whether an upright BM stimulus appeared among the dynamic noises to test their social cognition, as well as do a Mini-Mental State Examination to test their general cognition. The two tests were performed at both 1-day before and 7-day after the surgery. Results showed that 31.25% of patients exhibited BM perception deficit after anesthesia and surgery relative to before anesthesia and surgery, implying that social cognitive dysfunction existed. Meanwhile, social cognitive dysfunction was independent from delayed neurocognitive recovery.

The applause sign in elderly patients with idiopathic normal pressure hydrocephalus

Applause sign (AS) was shown to be an indicator of frontal subcortical dysfunction in many neurodegenerative diseases. Idiopathic normal pressure hydrocephalus (INPH) is one of those in which frontosubcortical disconnection can be displayed. We aimed to examine the presence of AS in the elderly patients with INPH and its possible diagnostic role in the frontal dysfunction commonly seen in the disease. Sixty-six patients diagnosed with probable INPH, 32 with behavioral variant of frontotemporal dementia (bvFTD) and 325 healthy elderly subjects were included in this cross-sectional and retrospective study. AS was evaluated with the clapping test. Patients with INPH were further assessed with frontal assessment battery (FAB), Stroop test, verbal fluency test and clock drawing test (CDT). The concentration of total amyloid-β 42 (Aβ42), Aβ40, total (t) tau and phosphorylated (p)-tau proteins were also measured in the cerebrospinal fluid (CSF). AS was observed in all groups (40% in bvFTD, 28.8% in INPH, 1.2% in controls, respectively). It was significantly more frequent in patients with bvFTD and INPH as compared to the controls (p < 0.001, for each). The frequency was similar in the patients with bvFTD and INPH (p = 0.802). Significant differences were found between the AS(+) and (−) INPH patients with regards to FAB, Stroop test-errors and verbal fluency test, except for the CSF proteins. AS can be used as a simple, useful and rapid clinical test that investigates executive dysfunction in elderly patients with INPH in both inpatient and outpatient settings.

Preoperative neutrophil-lymphocyte ratio, an independent risk factor for postoperative cognitive dysfunction in elderly patients with gastric cancer.

This study aimed to investigate the potential risk factors for postoperative cognitive dysfunction (POCD) in elderly patients with gastric cancer (GC) after radical gastrectomy. In total, 221 elderly patients with GC who were scheduled to undergo selective radical gastrectomy in our hospital were enrolled in this study. To define early POCD, the neuropsychological assessment was carried out 1 day before surgery and 7 days after surgery. Receiver operating characteristic curve analysis was carried out to evaluate the predicative and cut-off values of risk factors, including neutrophil-lymphocyte ratio (NLR) for early POCD. The univariate and multivariate logistic regression analyses were performed to investigate risk factors for early POCD. Of the 221 enrolled elderly patients with GC, 42 were identified as early POCD with an incidence of 19.0% (42 of 221). Receiver operating characteristic curve analysis indicated that NLR was a significant predictor for POCD with a cut-off value of 2.50 and an area under the curve of 0.711 (95% confidence interval: 0.624-0.798, P < 0.001). Preoperative NLR (≥2.50) was the only independent risk factor associated with POCD (odds ratio: 2.44, 95% confidence interval: 1.52-3.68, P = 0.013) by the multivariate logistic regression analysis. Preoperative NLR level was an independent risk factor for POCD in elderly patients with GC undergoing curative resection. Geriatr Gerontol Int 2020; 20: 927-931.

Use of Light Therapy for Insomnia in the Elderly: Role of Circadian Rhythm Disorders

Here, we review the unique mechanisms that underlie insomnia in elderly patients and how it relates to circadian dysfunction in order to provide a practical approach to light therapy in this population. While the connection between aging and insomnia has long been recognized, postmortem and recent biomarker studies have advanced our understanding of the underlying mechanisms. Most recently, studies utilizing PET tracers have supported an association of sleep disturbance with neurodegenerative changes prior to the onset of cognitive impairment. These changes may result in reduced circadian amplitude and other circadian disturbances. Recent studies added to a body of literature suggest that circadian dysfunction in elderly patients can be targeted with light therapy to improve sleep quality, timing, and duration. Circadian dysfunction plays an important role in the etiology of insomnia in the elderly. Even in the absence of cognitive decline, neurodegenerative changes in the brain are a common consequence of aging that may contribute to circadian dysfunction and insomnia generally. Light therapy may be a useful tool in addressing the underlying impact of aging on sleep and can be used in varying ways depending on the patient’s unique presentation.

Effect of General Versus Spinal Anesthesia on Postoperative Delirium and Early Cognitive Dysfunction in Elderly Patients.

BackgroundPostoperative cognitive dysfunction (POCD) and delirium are common in the elderly patients, given the controversial results of previous studies about the impact of anesthesia type on the occurrence of these complications.ObjectivesThis study was planned to compare the effects of general and spinal anesthesia on the prevalence of POCD and delirium.MethodsA single-blind non-randomized clinical trial. Setting was in two academic hospitals. Ninety-four patients over 50 years old scheduled for hip fracture fixation. Patients were divided into two groups to receive either general (GA) or spinal (SA) anesthesia. Both Mini-Mental State examination (MMSE) and Wechsler tests were used before the operation and 3 times postoperatively to assess the cognitive function and detect early POCD. The DSM-IV criteria were also used for the diagnosis of delirium. The incidence of delirium and POCD and their precipitating factors were compared between the two groups.ResultsNinety-four patients with a mean age of 67.12 years were studied. The overall prevalence of POCD and delirium was 17.02%; however, it was significantly higher in the GA group rather than the SA group, 29.7%, and 4.25%, respectively (P < 0.001). There was a significant relationship between age (P = 0.048), ASA class (P = 0.034), and educational level with the incidence of POCD, meaning that the probability of developing cognitive impairment decreases with patients’ higher level of education and lower ASA-physical status. Also, the rate of POCD in men was significantly higher than in women (P = 0.026).ConclusionsThe finding of this study showed that, if there is no specific contraindication, neuraxial anesthesia may be preferred over general anesthesia in elderly patients.

Correlation Between Intestinal Microflora and Gastrointestinal Dysfunction in Elderly Patients with Sepsis

Multiple organ dysfunction syndrome (MODS) is a key factor that leads to death in elderly patients with sepsis. Therefore, early prevention and treatment of gastrointestinal dysfunction (GIDF) in elderly patients with sepsis is an important measure to prevent MODS occurrence. This research explores the correlation between intestinal microflora and GIDF in elderly patients with sepsis and provides ideas for the prevention and treatment of GIDF in elderly patients with sepsis. In this study, 152 patients with sepsis (122 patients with sepsis and GIDF) treated in the Third Affiliated Hospital of Yunnan University of Chinese Medicine from January to September 2019 were selected as the sepsis group and 100 elderly who had normal physical examination results were selected as the control group. The common intestinal microflora of the two groups was compared. Patients with sepsis and GIDF were treated as the GIDF group and the other patients with sepsis were treated as the non-GIDF group. The common intestinal microflora, gastrointestinal indicators, serum inflammatory factors, and immune function indices were compared between the two groups. Correlation analysis of the observed indices with statistical significance was carried out. The results showed 152 patients with sepsis and 122 patients with sepsis and GIDF; thus, the incidence of sepsis with GIDF was 80.26%. The total average score of sepsis with GIDF was 3.61±0.09. There was no statistically significant difference in GIDF scores of patients ages 65–75 and &gt; 75 years old. The number of Bifidobacterium and Lactobacillus in elderly patients with sepsis was lower and the number of Escherichia coli was higher than in the control group. In elderly patients with sepsis, the number of Bifidobacterium and Lactobacillus in the GIDF group was lower and the number of E. coli was higher than in the non-GIDF group. White blood cell (WBC) count, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), gastrin (GAS), and diamine oxidase (DAO) in GIDF patients were higher and motilin (MOT), CIT (CIT), CD4+, and CD8+ were lower than in the non-GIDF group. WBC count, PCT, CRP, TNF-α, GAS, and DAO were negatively correlated with the number of Bifidobacterium and Lactobacillus but positively correlated with E. coli. MOT, CIT, CD4+, and CD8+ were positively correlated with the number of Bifidobacterium and Lactobacillus but negatively correlated with E. coli. There was a negative correlation between Bifidobacterium and Lactobacillus and GIDF score and a positive correlation between E. coli and GIDF score. Therefore, the change in the intestinal microflora in elderly patients with sepsis is related to GIDF.

COGNITIVE DYSFUNCTION AS A FACTOR RESTRICTING THE APPLICATION OF ACCELERATED REHABILITATION PROGRAMS FOR ELDERLY AND SENIOR PATIENTS IN OPERATIVE GYNECOLOGY

Aim: to identify risk groups for the formation of cognitive dysfunction in elderly patients after gynecological operations. Research base: City Clinical Hospital named after S.P. Botkin, Moscow, Russian Medical Academy of Continuing Professional Education. The risk groups for the formation of cognitive dysfunction in elderly and senior patients after gynecological operations are determined. Hospitalization was carried out just before the operation, the postoperative hospital bed rest varied from 2 to 4 days. Where possible, the principles of FastTrack technology were applied in the perioperative period. Materials and methods. The study involved 60 elderly and senior female patients after menopause from the age of 50 to 85 years (75,2 ± 6,3 years), who underwent surgery under conditions of endotracheal anesthesia due to benign pathology (ovarian neoplasms, genital prolapse). The principles of FastTrack – an accelerated path in surgery were applied. Before the operation and on the 2nd day after the operation, testing was performed on the MMSE (Mini-mental State Examination) scale, as well as on the questionnaire to identify Spielberger-Hanin personal and reactive anxiety. Results. It has been proven that the frequency of postoperative cognitive dysfunction increases in proportion to the age of the patients and often depends on the type of anesthetic benefit and the severity of the operation. In the group of women aged from 50 to 60, no initial cognitive impairment was found, 18 % of patients after 60 years of age have cognitive impairment, and 5 % have mild dementia. The older the patient, the more cases of postoperative cognitive impairment develops/worsens, and high levels of anxiety remain. Early discharge in such cases can cause problems. Conclusion. In risk groups, especially in patients older than 70 years with signs of widespread atherosclerosis, cerebrovascular accidents, and a history of brain injuries, it is necessary to accurately identify signs of cognitive impairment and promptly involve a neurologist and clinical psychologist to correct them, which will significantly improve the postoperative period and reduce the anxiety level

1159 Sleep Traits And Incident Delirium During A Decade Of Follow-up In 173,000 Participants

Abstract Introduction Delirium is an acute decline in attention and cognition that is with associated long-term cognitive dysfunction in elderly patients. Accumulating evidence points to strong associations between sleep health and disorders of the brain. We tested whether baseline sleep duration, chronotype, daytime dozing, insomnia or sleep apnea predict incident delirium during hospitalization. Methods We studied participants from the UK Biobank who have been followed for up to 10 years until 2017. We included 173,221 participants (mean age 60±5; range 50-71 at baseline) who had at least one episode of hospitalization/surgery and were free from prior episodes of delirium. Delirium diagnosis, hospitalization and surgical events were derived using ICD-10 coding. Multivariate logistic regression models were performed to examine the associations of self-reported baseline sleep duration (&amp;lt;6hrs/6-9h/&amp;gt;9h), daytime dozing (often/rarely), insomnia (often/rarely) and presence of sleep apnea (ICD-10 and self-report) with incident delirium during follow-up. Models were adjusted for demographics, education, Townsend deprivation index, and major confounders (number of hospitalizations/surgical procedures, BMI, diabetes, major cardiovascular diseases and risk factors, major neurological diseases, major respiratory diseases, cancer, alcohol, depression/anxiety, sedatives/sleep aides, antipsychotics, steroids and opioids). Results In total, 1,023 (5.7 per 1,000 subjects) developed delirium. A prior diagnosis of sleep apnea (n=1,294) saw almost a two-fold increased odds (OR 1.96, 95% CI: 1.30-2.30 p=0.001) while those who often had daytime dozing were also at increased risk (OR 1.35, 95% CI: 1.02-1.80, p=0.025). Both these effects were independent of each other. No independent effects on incident delirium were observed from sleep duration, insomnia, or chronotype. Conclusion Certain sleep disturbances, in particular sleep apnea and daytime dozing, are independently associated with an increased risk for developing delirium. Further work is warranted to examine underlying mechanisms and to test whether optimizing sleep health can reduce the risk of developing delirium. Support This work was supported by NIH grants T32GM007592, RF1AG064312, and RF1AG059867.

Functional characterization of multifunctional ligands targeting acetylcholinesterase and alpha 7 nicotinic acetylcholine receptor

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cholinergic dysfunction, provoking memory loss and cognitive dysfunction in elderly patients. The cholinergic hypothesis provided over the years with molecular targets for developing palliative treatments for AD, acting on the cholinergic system, namely, acetylcholinesterase and α7 nicotinic acetylcholine receptor (α7 nAChR). In our synthetic work, we used “click-chemistry” to synthesize two Multi Target Directed Ligands (MTDLs) MB105 and MB118 carrying tacrine and quinuclidine scaffolds which are known for their anticholinesterase and α7 nAChR agonist activities, respectively. Both, MB105 and MB118, inhibit human acetylcholinesterase and human butyrylcholinesterase in the nanomolar range. Electrophysiological recordings on Xenopus laevis oocytes expressing human α7 nAChR showed that MB105 and MB118 acted as partial agonists of the referred nicotinic receptor, albeit, with different potencies despite their similar structure. The different substitution at C-3 on the 2,3-disubstituted quinuclidine scaffold may account for the significantly lower potency of MB118 compared to MB105. Electrophysiological recordings also showed that the tacrine precursor MB320 behaved as a competitive antagonist of human α7 nAChR, in the micromolar range, while the quinuclidine synthetic precursor MB099 acted as a partial agonist. Taken all together, MB105 behaved as a partial agonist of α7 nAChR at concentrations where it completely inhibited human acetylcholinesterase activity paving the way for the design of novel MTDLs for palliative treatment of AD.

SUN-457 ELDERLY ONSET RAPIDLY PROGRESSIVE RENAL DYSFUNCTION WITH KIDNEY ENLARGEMENT AND TUBULOINTERSTITIAL INJURY MIGHT BE A NEW DISEASE ENTITY OF CILIOPATHY

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of uncommon genetic disorders characterized by slowly progressive decline in kidney function and autosomal dominant inheritance. ADTKD is usually described as not showing enlarged kidneys. However, there have been several reports of rapidly progressive renal dysfunction in elderly patients with bilateral kidney enlargement and ADTKD-like histology in Japan. Here we reported three cases with enlarged kidneys who have undergone dialysis with rapid progression and performed analysis of gene panel for target sequence of inherited kidney diseases. CASE PRESENTATION: 【Cases 1】 Eighty-four-year-old Japanese woman without family history of kidney diseases was noted to have renal dysfunction of unknown etiology 1 year prior to admission. She had developed progressive renal dysfunction (Cr 3.7mg/dL). Her abdominal CT revealed enlarged kidneys and histological findings showed marked tubular dilatation with extensive fibrosis in the interstitium, consistent with ADTKD. She was initiated hemodialysis 3 month after. 【Cases 2】 Seventy-four-year-old woman suffering from ulcerative colitis was noted to have mild renal impairment (Cr 1.1mg/dL) 1 year prior to admission. She developed progressive renal dysfunction (Cr 3.6mg/dL). Her serial abdominal CT showed enlarged kidneys on admission, but the kidneys were not enlarged one year ago. Her histological findings revealed consistent with ADTKD. She was initiated hemodialysis 5 month after. 【Cases 3】 Eighty-year-old woman was noted to have renal dysfunction (Cr 1.9mg/dL) 1 year prior to admission. She had developed progressive renal dysfunction (Cr 3.3mg/dL). Her CT showed enlarged kidneys and histological findings revealed consistent with ADTKD. She was initiated hemodialysis 1 year after. DISCUSSIONS: We searched the related literature with similar characteristics such as elder and rapid progression, enlarged kidneys, dilated tubules. And we found 15 cases which were only reported in Japan and compared among them including our 3 cases. Most cases are sporadic and seem to be non-inherited. The age at renal biopsy was 70 years. Before renal biopsy, a rate of Cr elevation was 0.5 mg / dL / month, and renal biopsy was performed at 4.1 mg / dL of Cr. Urine protein were positive in all cases, urine occult blood was positive in 50% cases. Urinary beta 2 microglobulin was 12145 ng/ml. Kidney enlargement was described in all cases except 2 undescribed cases. Renal biopsy findings showed minor glomerular changes and marked dilated renal tubules and interstitial fibrosis. The dilated tubules were detected as distal tubules by immunohistochemical staining. Electron microscopy showed irregularities, thinning and partial thickening of the tubular basement membrane. These pathological findings were compatible with traditional ADTKD. After renal biopsy, all cases showed rapidly progressive renal dysfunction with a rate of Cr elevation at 1.2 mg / dL / month and initiated dialysis in 4.1 months. Analysis of gene panel for target sequence of inherited kidney diseases was performed in 6 cases and no known gene mutation (including ADTKD-MUC1and ADTKD-UMOD) was detected. Elderly onset rapidly progressive renal dysfunction with enlarged kidneys and tubulo-interstitial injury might be a new disease entity of ciliopathy unlike traditional ADTKD.

Intravenous parecoxib for early postoperative cognitive dysfunction in elderly patients: evidence from a meta-analysis

ABSTRACT Background Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor parecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the efficacy and safety of parecoxib on early POCD in geriatric patients. Objective This study was performed to evaluate the efficacy and safety of parecoxib for early postoperative cognitive dysfunction (POCD) in elderly patients. Methods Comprehensive literature search based on six electronic databases was applied to retrieve all related randomized controlled trials (RCTs). Two independent reviewers screened each article for eligibility according to the predetermined inclusion criteria. The Cochrane’s Tool was applied to evaluate the methodological quality of included studies. RevMan 5.3 was used to conduct meta-analysis. Results Eight RCTs comprising a total of 1106 subjects prepared for orthopedic surgical operation were selected. All the identified RCTs were conducted in China. The methodological qualities of included studies were judged to be medium to high. The integrated data showed that perioperative intravenous parecoxib could remarkably reduce the incidence of POCD with improved Mini-Mental State Examination (MMSE) score. Parecoxib could significantly reduce the concentrations of interleukin-6, but results regarding the changes in tumor necrosis factor-alpha, C-reactive protein, and S100β levels remained inconsistent. Conclusion Perioperative parecoxib administration is effective in reducing the incidence of POCD and improving the MMSE score compared with control. However, the beneficial effect of parecoxib has been tested only in the Chinese population. Future RCTs in western countries with larger-scale and more comprehensive neurological tests are needed.

Sevoflurane anesthesia-mediated oxidative stress and cognitive impairment in hippocampal neurons of old rats can be ameliorated by expression of brain derived neurotrophic factor

Postoperative cognitive dysfunction in elderly patients has been related to neurodegenerative disorders and mortality. Sevoflurane anesthesia has been implicated in both postoperative cognitive dysfunction and neurotoxicity. Given the advantages of using inhaled anesthetics like sevoflurane, it is important to understand how their usage results in neurotoxicity and subsequently devise ways to circumvent or attenuate the anesthetic-mediated induction in neurotoxicity. We have used an aged rat model to investigate the molecular mechanisms by which sevoflurane inhalation results in neurotoxicity and whether modulation of these molecular mechanisms can inhibit or attenuate neurotoxicity and cognitive learning and memory impairment in these animals. Low- or high-dose of sevoflurane resulted in reactive oxygen species generation, increased NADPH oxidase protein expression, apoptosis and autophagy. Sevoflurane inhalation resulted in significant inhibition of brain derived neurotrophic factor (BDNF) and cognitive impairment. And the activation of PI3K/Akt/mTOR signaling pathways are attenuated in sevoflurane-mediated anesthesia. Adeno-associated virus (AAV)-mediated expression of Bdnf, but not controls EGFP, attenuated sevoflurane-induced oxidative stress and cognitive impairment in the rats. Our results highlight that AAV-mediated gene therapy might offer a potential therapeutic opportunity to treat post-operative cognitive impairment resulting from inhaled anesthetics.

Serum Metabolomics of Early Postoperative Cognitive Dysfunction in Elderly Patients Using Liquid Chromatography and Q-TOF Mass Spectrometry.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. However, the diagnosis of POCD is not very satisfactory as no specific biomarkers have been classified. It is necessary to identify new diagnostic markers to better understand the pathogenesis of POCD. We performed liquid chromatography with a time-of-flight mass spectrometer- (LC/Q-TOF-MS-) based metabolomics study to investigate POCD. A total of 40 metabolites were differentially expressed between POCD and non-POCD patients. In this study, we investigated whether phosphatidylserine (PS) (17:2/0:0), with an area under the curve value of 0.966, was a potential sensitive and specific biomarker for the diagnosis and prognosis of POCD. Pathway analysis showed that fatty acid metabolism, lipid metabolism, and carnitine metabolism were significantly altered in POCD. Network analysis indicated that nitric oxide signaling, PI3K-AKT signaling, mTOR signaling, and mitochondrial dysfunction were related to the pathogenesis of POCD. This study showed that metabolic profiling was meaningful when studying the diagnosis and pathogenesis of POCD.

Postoperative cognitive dysfunction in elderly patients undergoing hip arthroplasty.

Even after successful hip arthroplasty, elderly patients who have undergone this procedure remain subject to cognitive decline and may collectively develop postoperative cognitive dysfunction (POCD). However, no consensus exists as to the risk factors resulting in a higher likelihood that a patient may present with this complication, and the aetiology of POCD is not well understood. We conducted a systematic review of papers concerning the influence of POCD-related risk factors in patients undergoing hip arthroplasty but limited the literature search to papers in English. A systematic and electronic search for manuscripts in the PubMed database was performed in order to identify all studies in which the risk factors for POCD were investigated. Articles were also obtained from the authors' files. Keywords for the search were postoperative cognitive dysfunction/change/impairment/decline/deficit, elderly/older/aged patients, and hip arthroplasty/replacement surgery. The evidence published to date suggests that POCD is a multifactorial disease, which includes an individual patient's characteristics, surgery, type of anaesthesia, and pain levels. All of these factors can increase the risk of POCD incidence. There are a number of factors that appear to influence the risk of early cognitive dysfunction after hip arthroplasty. Nevertheless, the specific mechanism and explicit risk factors associated with this cognitive dysfunction are not completely understood. Hip arthroplasty has made it possible for older patients to find relief from pain and improve their function, whereas it also increases the risk for suffering POCD that may affect these patients' quality of life and increase their mortality. Therefore, it is worthwhile investigating the mechanism of POCD in future studies in order to prevent and treat this condition.

Effect Of Aspirin Preoperative on Postoperative Cognitive Dysfunction In Elderly Patients Undergoing Knee Arthroplasty

Effect Of Aspirin Preoperative on Postoperative Cognitive Dysfunction In Elderly Patients Undergoing Knee Arthroplasty

The incidence of postoperative cognitive dysfunction in elderly patients underwent elective surgery at Sanglah General Hospital

Background: Postoperative cognitive dysfunction (POCD) causes an increase in social and economic burdens because of the prolonged length of stay in the hospital, increased costs, and decreased quality of life. No data on POCD has ever been recorded in Indonesia. The goal of this study was to determine the incidence of POCD in elderly people at Sanglah General Hospital, Indonesia. Patients and Methods: This is a descriptive study conducted at Sanglah General Hospital in 2018. Inclusion criteria included patients of 60 years old or more who came to anesthesia preoperative clinic with the American Society of Anesthesiologists physical status 1 and 2. Cognitive functions were assessed three times: 1 day before the surgery, 2 days after the surgery, and 4 weeks after the surgery. POCD was defined as an at least 20% decreased result of two out of three instruments used. Results: The study included 84 participants consisting of 52 males and 32 females. The mean age was 66.0 ± 5.1 years. Most participants were elementary school graduates (34.5%) and high school graduates (27.4%). There were 7 (8.3%) patients who developed POCD within 48 h and 4 weeks postoperatively. Conclusion: The incidence of POCD at Sanglah General Hospital was 8.33% both at 48 h and 4 weeks postoperatively.

Association of global DNA hypomethylation with post-operative cognitive dysfunction in elderly patients undergoing hip surgery.

Post-operative cognitive dysfunction (POCD) is a decline of cognitive status that commonly occurs after surgery in elderly patients. Whether DNA methylation is associated with the development of POCD remains unclear. Subjects (N=124) older than 65years-of-age undergoing hip replacement surgery were enrolled. A battery of neuropsychiatric tests was used to examine the perioperative cognitive function of the patients. Early POCD was analyzed using the reliable change index (RCI), and subjects were diagnosed with POCD if RCI<-1.96. Peripheral leukocyte DNA was isolated, and DNA methylation was measured via 5-methylcytosine (mC) using Elisa. Twenty-four patients (19.4%) developed early POCD. There was no difference in baseline 5-mC levels by POCD status. The 5-mC levels significantly decreased on day 7 after surgery in patients who developed early POCD (P=.004), but did not change in non-POCD patients. Moreover, post-operative 5-mC levels were significantly lower in POCD patients than those in non-POCD patients (P=.003). Bivariate logistic models adjusted for age, gender, BMI, duration of anesthesia, and education level clearly demonstrated an independent association between post-operative 5-mC level and early POCD. Post-operative global hypomethylation of leukocyte DNA was associated with the development of early POCD. ClinicalTrial, NCT02965235. Registered 16 November 2016, https://www.clinicaltrials.gov/ct2/results?term=NCT02965235&rank=1#rowId0.