Types Of Cognitive Impairment Research Articles

Low serum apelin levels are associated with mild cognitive impairment in Type 2 diabetic patients

BackgroundApelin is a new adipokine that is secreted by adipocytes, and is associated with insulin resistance (IR), inflammation, and obesity. This study was designed to investigate the role of apelin in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI).MethodsA total of 235 patients with T2DM were included. The cognitive function of patients was evaluated using Montreal Cognitive Assessment (MoCA) tool, then patients were divided into MCI group and non-MCI group according to the MoCA score. Blood sample was analyzed for the level of apelin by enzyme-linked immunosorbent assay (ELISA).ResultsThe MCI group (n = 73) presented lower serum apelin levels compared with the patients with normal cognitive function (P < 0.001). Apelin levels showed significantly negative correlation with diabetes duration, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C, creatinine and high sensitivity C-reactive protein (hs-CRP), and positive correlation with high-density lipoprotein cholesterol (HDL-C) and brain-derived neurotrophic factor (BDNF). Multivariable logistic regression analysis indicated that serum apelin (OR = 0.304, 95%CI: 0.104–0.886, P = 0.029), as well as education levels, diabetes duration, cardiovascular disease, serum HbA1c, HDL-C, creatinine, and BDNF, were independent risk factors of MCI in patients with T2DM.ConclusionsSerum apelin level is reduced in T2DM patients with MCI. Apelin might has protective effect against cognitive impairment and serve as a serum biomarker of T2DM.

How Can Animal Models Inform the Understanding of Cognitive Inflexibility in Patients with Anorexia Nervosa?

Deficits in cognitive flexibility are consistently seen in patients with anorexia nervosa (AN). This type of cognitive impairment is thought to be associated with the persistence of AN because it leads to deeply ingrained patterns of thought and behaviour that are highly resistant to change. Neurobiological drivers of cognitive inflexibility have some commonalities with the abnormal brain functional outcomes described in patients with AN, including disrupted prefrontal cortical function, and dysregulated dopamine and serotonin neurotransmitter systems. The activity-based anorexia (ABA) model recapitulates the key features of AN in human patients, including rapid weight loss caused by self-starvation and hyperactivity, supporting its application in investigating the cognitive and neurobiological causes of pathological weight loss. The aim of this review is to describe the relationship between AN, neural function and cognitive flexibility in human patients, and to highlight how new techniques in behavioural neuroscience can improve the utility of animal models of AN to inform the development of novel therapeutics.

Higher Serum Soluble TREM2 as a Potential Indicative Biomarker for Cognitive Impairment in Inadequately Controlled Type 2 Diabetes Without Obesity: The DOR-KyotoJ-1.

ObjectiveType 2 diabetes is a risk factor for dementia. We investigated whether serum levels of soluble triggering receptor expressed on myeloid cell 2 (sTREM2), a soluble form of the cell surface receptor TREM2, were predictive of cognitive impairment in type 2 diabetes without obesity.MethodsA total of 166 Japanese patients with type 2 diabetes without obesity were followed-up for 2 years. We measured clinical parameters, assessed cognitive function using the mini-mental state examination (MMSE), quantified and divided serum sTREM2 levels into quartiles, and examined the longitudinal associations.ResultsDuring the follow-up, HbA1c levels were elevated in 98 patients and decreased in 68 patients. In the HbA1c-elevated group, higher sTREM2 levels at baseline showed a significant association with a greater tendency for reduction in MMSE scores (P for trend = 0.015), whereas they were not significantly associated with other examined parameters. In the HbA1c-decreased group, there was no significant association between sTREM2 levels at baseline and changes in MMSE scores, but higher sTREM2 levels at baseline were significantly associated with a greater tendency for reduction in waist circumference (P for trend = 0.027), homeostasis model assessment of insulin resistance (P for trend = 0.039), and sTREM2 levels (P for trend = 0.023).ConclusionsGlycemic control is suggested to be important in preventing cognitive impairment in patients with type 2 diabetes without obesity. Higher serum sTREM2 levels would be a predictive marker for cognitive impairment in inadequately controlled type 2 diabetes without obesity.

Advances in SGLT2 Inhibitor Research on Cognitive Impairment in Type 2 Diabetes

Advances in SGLT2 Inhibitor Research on Cognitive Impairment in Type 2 Diabetes

Urolithin A Attenuates Diabetes-Associated Cognitive Impairment by Ameliorating Intestinal Barrier Dysfunction via N-glycan Biosynthesis Pathway.

This study aims to investigate the effect of Urolithin A (UA) on diabetes-associated cognitive impairment in type 2 diabetes mellitus (T2DM) mouse model induced by high-fat diet (HFD) and streptozotocin (STZ). The UA-treated T2DM mice display an attenuated cognitive impairment as well as reduced levels of metabolic endotoxemia and proinflammatory cytokines in serum. A systemic restraint of gut/brain inflammation in UA-treated T2DM mice is also observed as the downregulation of TLR4 and Myd88 in colon along with the inhibition of GFAP, Iba-1, NLRP3, and inflammation-related genes in brain. Moreover, UA ameliorates gut barrier dysfunction by upregulating tight-junction proteins levels. Furthermore, UA restores the hyperglycemia-mediated downregulation of genes involved in N-glycan biosynthesis both in vivo and in vitro, which plays a crucial role in barrier integrity. Although UA shares similar beneficial effects on diabetes with metformin, unlike metformin, the effect of UA is independent of gut microbiome and short chain fatty acids. Taken together, these data suggest that feeding UA can attenuate diabetes-associated cognitive impairment by ameliorating systemic inflammation and intestinal barrier dysfunction via N-glycan biosynthesis pathway. The study implies UA as a potential novel pharmaceutic target for diabetes therapy via manipulating gut-brain axis and N-glycan metabolism.

Cognitive Impairment in Type 2 Diabetes Mellitus.

ObjectiveTo determine the incidence of cognitive impairment established on the mini-mental state assessment in type 2 diabetic patients presenting at Holy Family Hospital, Rawalpindi.Materials and methodsThis cross-sectional descriptive study was carried out from June 2019 to December 2019. Individuals with a diagnosis of type 2 diabetes mellitus were included, and detailed history, physical examination, and biochemical variables were noted. They were assessed through Mini-Mental State Examination (MMSE) (Urdu translation) to look for the primary outcome variable, i.e., cognitive impairment. All patients with type 2 diabetes mellitus diagnosed at least one year back, irrespective of gender, were included in this investigation. Patients with a previous history of head injury, epilepsy, stroke, those on an antidepressant or antipsychotic medications, those with deranged renal function tests, and those already diagnosed with dementia were excluded from the study.ResultsThree hundred thirty-two patients meeting the inclusion criteria were included in the study. The mean ± standard deviation age of the study population was 65.32 ± 11.33 years, with maximum age being 80 years and the minimum being 50 years. Two hundred patients (60.24%) were below 65 years of age, and 132 patients (39.76%) were 65 years of age or above. Two hundred sixteen (65.06%) were males, and 116 (34.96%) were females. The mean duration of diabetes mellitus (DM) was 10.17 ± 4.81. The mean MMSE score was 22.69 ± 5.26. Out of 332 patients, 81 (24.4%) patients had cognitive impairment. Patients who were 65 or older had a significantly higher proportion of cognitive impairment, compared to those below 65 years of age (p-value = 0.0214). There was no significant difference in the proportion of cognitively impaired patients between males and females (p-value = 0.2497). Similarly, there was no significant difference between those who were diagnosed with type 2 diabetes for 10 years or more and those who were diagnosed less than 10 years ago (p-value = 0.3791).ConclusionCognitive impairment is common in individuals having type 2 diabetes mellitus. It is also associated with the increasing age of diabetic patients. However, cognitive impairment in type 2 diabetes mellitus is not associated with gender. In addition, there is no significant difference in cognitive impairment between the patients who were diagnosed with diabetes more than 10 years ago and those who had it diagnosed less than 10 years ago.

Cognitive Impairment in Type 2 Diabetes Mellitus: An Observational Study from Lower Middle-Income Country

Cognitive Impairment in Type 2 Diabetes Mellitus: An Observational Study from Lower Middle-Income Country

Age Related Prevalence of Mild Cognitive Impairment in Type 2 Diabetes Mellitus Patients in the Indian Population and Association of Serum Lipids With Cognitive Dysfunction.

The magnitude of type 2 diabetes mellitus (T2DM) is ever-increasing in India, and at present, ~77 million people live with diabetes. Studies have established that T2DM increases the risk of neurodegenerative disorders. This study aimed to determine the age-related prevalence of mild cognitive impairment (MCI) in T2DM patients in the Indian population and to identify link between cognitive dysfunction in T2DM patients and serum lipid composition through untargeted and targeted lipidomic studies. Using a cross-sectional study, we evaluated 1278 T2DM patients with Montreal cognitive assessment test (MoCA) and digit symbol substitution test (DSST) for cognitive functions. As per MoCA, the prevalences of MCI in T2DM patients in age groups below 40, 41-50, 51-60, 61-70, 71-80 and 81-90 years were 13.7, 20.5, 33.5, 43.7, 57.1 and 75% with DSST scores of 45.8, 41.7, 34.4, 30.5, 24.2 and 18.8% respectively. Binomial logistic regression analysis revealed serum HbA1c ≥ 7.51, duration of T2DM over 20 years, age above 41 years, and females were independent contributors for cognitive dysfunction in T2DM patients. Preliminary studies with untargeted lipidomics of the serum from 20 T2DM patients, including MCI and normal cognition (NC) group, identified a total of 646 lipids. Among the identified lipids, 33 lipids were significantly different between MCI and NC group, which comprised of triglycerides (TGs, 14), sphingolipids (SL, 11), and phosphatidylcholines (PC, 5). Importantly, 10 TGs and 3 PCs containing long-chain polyunsaturated fatty acids (PUFA) were lower, while 8 sphingolipids were increased in the MCI group. Since brain-derived sphingolipids are known to get enriched in the serum, we further quantified sphingolipids from the same 20 serum samples through targeted lipidomic analysis, which identified a total of 173 lipids. Quantitation revealed elevation of 3 species of ceramides, namely Cer (d18:1_24:1), Hex1Cer (d16:0_22:6), and Hex2Cer (d28:1) in the MCI group compared to the NC group of T2DM patients. Overall, this study demonstrated an age-related prevalence of MCI in T2DM patients and highlighted reduced levels of several species of PUFA containing TGs and PCs and increased levels of specific ceramides in T2DM patients exhibiting MCI. Large-scale lipidomic studies in future could help understand the cognitive dysfunction domain in T2DM patients, while studies with preclinical models are required to understand the functional significance of the identified lipids.

2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione Ameliorates Diabetic Cognitive Impairment Through Inhibiting Hif3α and Apoptosis.

Diabetes mellitus (DM) is an independent risk factor for cognitive impairment. Although the etiology of diabetic cognitive impairment is complex and multifactorial, the hippocampus neuronal apoptosis is recognized as a main cause of diabetes-induced cognitive impairment. 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) was purified from the roots of Averrhoa carambola L. Previous research demonstrated that DMDD was safe and effective in delaying some diabetic complications. However, the efficacy of DMDD to ameliorate diabetic cognitive impairment in type 2 diabetes mice has not been reported. In the present study, the behavioral evaluation was performed by Y maze and novel object recognition in db/db mice. Gene expression profiles were detected using mouse lncRNA microarray analysis in the hippocampi of db/db mice. Changes in the neurodegeneration-associated proteins and the apoptosis-related proteins were determined in both db/db mice and high glucose-treated HT22 cells by Western blotting. We observed that DMDD treatment significantly ameliorated the spatial working memory and object recognition memory impairment in db/db mice. Further study showed that neurodegeneration-associated protein tau was decreased after DMDD treatment in the hippocampi of db/db mice. Eleven lncRNAs and four mRNAs including pro-apoptotic gene Hif3a were significantly differently expressed after DMDD treatment in the hippocampi of db/db mice. The expression of Hif3a, cleaved parp, and caspase 3 proteins was significantly increased in the hippocampi of diabetic db/db mice compared with db/m control mice and then decreased after DMDD treatment. Similar beneficial effects of DMDD were observed in HG-treated HT22 cells. These data indicate that DMDD can alleviate cognitive impairment by inhibiting neuronal apoptosis through decreasing the expression of pro-apoptotic protein Hif3a. In conclusion, our study suggests that DMDD has great potential to be a new preventive and therapeutic compound for diabetic cognitive impairment.

Optical and electrophysiological techniques for functional assessment of vision system neuronal networks

We studied the two major channels of the vision system, which differ not only in their spatial-frequency characteristics but also in the sizes of the cellular structures that support the corresponding neuronal networks. We used a combination of optical and electrophysiological techniques to measure the properties of these channels in normal test subjects and in patients with various types of cognitive impairment. For electrophysiological measurements, a digital filter was used to generate stimuli with spatial-frequency responses for selective activation of each channel. Optical coherence tomography (OCT) and electrophysiological measurements in test subjects with various types of cognitive impairment were used to determine the relationship between morphological and functional changes in the vision system channel, which is primarily formed by the small-cell neuronal network and supports processing of high spatial frequencies.

Clinical and psychopathological features of patients with type II diabetes mellitus

Today, type II diabetes mellitus (T2DM) is considered to be the most important nosological cause of decreased cognitive functions. A number of studies have found that hyperglycemia and duration of diabetes are associated with cognitive deficits, with the prevalence of cognitive impairment in type 2 diabetes mellitus being 20% in men and 18% in women over 60 years of age.&#x0D; To achieve this goal, it was conducted a comprehensive clinical-psychopathological and psychodiagnostic examination of 82 patients with moderate type 2 diabetes mellitus (46 women and 36 men) aged 35.9±10.1 years in accordance with the principles of bioethics and deontology. The mean duration of diabetes was 7.9±5.2 years. The severity of diabetes in most cases was defined as moderate (84.1%), and in 15.9% of cases corresponded to severe. 30.2% of patients used insulin as a basic hypoglycemic therapy, 69.8% - tablets.&#x0D; According to the analysis of the emotional state of patients with T2DM were characterized by complaints of low, depressed mood (69.5% of examined patients), uncontrolled emotional reactions (46.2%), feelings of anxiety, constant internal tension (44.7%), paresthesias (29.1%), sleep-wake cycle disorders (56.2%), general weakness, lethargy and fatigue (58.2%), fatigue (90.0%), frequent mood swings, with a predominance of decreased mood background (23.3%), emotional lability with excessive vulnerability and sensitivity (16.6%), irritability (16.6%).&#x0D; The clinical and psychopathological structure of emotional disorders is represented by anxious (43.4%), depressive (26.6%), astheno-hypochondriac (19.8%), hysteroform (10.2%) syndromes. Clinical examination of patients with DM showed that more often (in 95.0% of cases) in patients with T2DM there is a decrease in memory of auditory and visual modality, impaired intellectual abilities, slow thinking, lack of attention and information processing.

An Inpatient Geriatrics Program with a Focus on Any Type of Cognitive Impairment Reduces Mortality.

No matter what type of cognitive impairment an older hospitalized patient has, the risk of mortality is increased. To describe a hospital-based geriatrics program with a focus on any type of cognitive impairment and to determine whether this program was associated with reduced mortality over time. Retrospective chart review of all patients age 70+ admitted during a 3-year period (2017-2019, N=20,401), to a 500-bed community-based hospital (Level 1 Trauma Center and Stroke Center). A multicomponent geriatrics program was developed and implemented throughout 2018 and included: geriatric consultation, data collection, review of the data with hospital leaders, a geriatrics task force, clinician education and a Delirium Unit. Monthly mortality rates for patients with and without cognitive impairment over the 3-year period. To control for other variables associated with mortality, pre-post implementation analyses were performed (2017 versus 2019). A linear regression analysis showed a significant downward trend in mortality over time for patients with cognitive impairment [R2=0.4, P<.0001, (correlation coefficient -0.6, 95% CI, -0.8 to -0.4)] but not among patients without cognitive impairment [R2=0.0, P=0.829, (correlation coefficient 0.0, 95% CI, -0.3 to 0.3)]. When controlling for other variables, there was still a decrease in mortality risk among patients with cognitive impairment. Although there are limitations to this study, a multicomponent geriatrics program with an emphasis on any type of cognitive impairment, may be associated with improved mortality.

Altered Hippocampal Subfields Volumes Is Associated With Memory Function in Type 2 Diabetes Mellitus

Objective: Cognitive impairment in type 2 diabetes mellitus (T2DM) patients is related to changes in hippocampal structure and function. However, the alternation of hippocampal subfields volumes and their relationship with cognitive function are unclear. This study explored morphological alterations in the hippocampus and its subfields in T2DM patients and their relationship with cognitive function.Methods: Thirty T2DM patients and 20 healthy controls (HCs) were recruited and underwent 3-dimensional, high-resolution T1-weighted sequence (3D-T1) and a battery of cognitive tests. Freesurfer 6.0 was performed to segment the hippocampus into 12 subregions automatically. Then relationships between hippocampal subfield volumes and neurocognitive scale scores in the T2DM group were evaluated.Results: Immediate memory scores on the auditory verbal learning test (AVLT) and Montreal Cognitive Assessment (MoCA) scores in T2DM patients were lower than in the HCs. T2DM patients showed that volumes of the bilateral hippocampus were significantly reduced, mainly in the bilateral molecular layer, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), cornu ammonis 4 (CA4), fimbria, and left subiculum and the right hippocampus amygdala transition area (HATA) compared to HCs. In addition, T2DM patients showed the FINS was negatively correlated with volume of left GC-ML-DG (r = −0.415, P = 0.035) and left CA4 (r = −0.489, P = 0.011); the FBG was negatively correlated with volume of right fimbria (r = −0.460, P = 0.018); the HOMA-IR was negatively correlated with volume of left GC-ML-DG (r = −0.367, P = 0.046) and left CA4(r = 0.462, P = 0.010). Partial correlation analysis found that the volume of right HATA in T2DM group was positively correlated with AVLT (immediate) scores (r = 0.427, P = 0.03).Conclusion: This study showed the volumes of multiple hippocampal subfields decreased and they were correlated with FINS, FBG and HOMA-IR in T2DM patients. We hypothesized that decreased hippocampal subfields volumes in T2DM patients was related to insulin resistance and impaired vascular function. In addition, we also found that abnormal hippocampal subfields volumes were related to memory function in T2DM patients, suggesting that reduced volumes in specific hippocampal subfields may be the potential mechanism of memory dysfunction in these patients.

Neural networks in the predictive diagnosis of cognitive impairment in type 1 and type 2 diabetes mellitus

Cognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognized as a serious complication of diabetes mellitus (DM) that affects patient well-being and disease management. Magnetic resonance imaging (MRI)-studies have shown varying degrees of cortical atrophy, cerebral infarcts, and deep white matter lesions. To explain the relationship between DM and cognitive decline, several hypotheses have been proposed, based on the variability of glycemia leading to morphometric changes in the brain. The ability to predict cognitive decline even before its clinical development will allow the early prevention of this pathology, as well as to predict the course of the existing pathology and to adjust medication regimens. To create a computer neural network model for predicting the development of cognitive impairment in DM on the basis of brain neuroimaging techniques. The study was performed in accordance with the standards of good clinical practice; the protocol was approved by the Ethics Committee. The study included 85 patients with type 1 diabetes and 95 patients with type 2 diabetes, who were divided into a group of patients with normal cognitive function and a group with cognitive impairment. The patient groups were comparable in age and duration of disease. Cognitive impairment was screened using the Montreal Cognitive Assessment Scale. Data for glycemic variability were obtained using continuous glucose monitoring (iPro2, Libre). A standard MRI scan of the brain was performed axially, sagittally, and coronally on a Signa Creator E, GE Healthcare, 1.5 Tesla, China. For MRI data processing we used Free Surfer program (USA) for analysis and visualization of structural and functional neuroimaging data from cross-sectional or longitudinal studies, and for segmentation we used Recon-all batch program directly. All statistical analyses and data processing were performed using Statistica Statsofi software (version 10) on Windows 7/XP Pro operating systems. The IBM WATSON cognitive system was used to build a neural network model. As a result of the study, cognitive impairment in DM type 1was predominantly of mild degree 36.9% (n=24) and moderate degree 30.76% (n=20), and in DM type 2 mild degree 37% (n=30), moderate degree 49.4% (n=40) and severe degree 13.6% (n=11). Cognitive functions in DM type 1 were impaired in memory and attention, whereas in DM type 2 they were also impaired in tasks of visual-constructive skills, fluency, and abstraction (p0.001). The analysis revealed differences in glycemic variability indices in patients with type 1 and type 2 DM and cognitive impairment. Standard MRI of the brain recorded the presence of white and gray matter changes (gliosis and leukoareosis). General and regional cerebral atrophy is characteristic of type 1 and type 2 DM, which is associated with dysglycemia. When building neural network models for type 1 diabetes, the parameters of decreased volumes of the brain regions determine the development of cognitive impairment by 93.5%, whereas additionally, the coefficients of glycemic variability by 98.5%. The same peculiarity was revealed in type 2 DM 95.3% and 97.9%, respectively. In DM type 1 and type 2 with cognitive impairment, elevated coefficients of glycemic variability are more frequently recorded. This publication describes laboratory and instrumental parameters as potential diagnostic options for effective management of DM and prevention of cognitive impairment. Neural network models using glycemic variability coefficients and MR morphometry allow for predictive diagnosis of cognitive disorders in both types of diabetes.

Observing Pain in Individuals with Cognitive Impairment: A Pilot Comparison Attempt across Countries and across Different Types of Cognitive Impairment.

Facial expression is a key aspect in observational scales developed to improve pain assessment in individuals with cognitive impairments. Although these scales are used internationally in individuals with different types of cognitive impairments, it is not known whether observing facial expressions of pain might differ between regions or between different types of cognitive impairments. In a pilot study, facial responses to standardized experimental pressure pain were assessed among individuals with different types of cognitive impairments (dementia, mild cognitive impairment, Huntington’s disease, and intellectual disability) from different countries (Denmark, Germany, Italy, Israel, and Spain) and were analyzed using facial descriptors from the PAIC scale (Pain Assessment in Impaired Cognition). We found high inter-rater reliability between observers from different countries. Moreover, facial responses to pain did not differ between individuals with dementia from different countries (Denmark, Germany, and Spain). However, the type of cognitive impairment had a significant impact; with individuals with intellectual disability (all being from Israel) showing the strongest facial responses. Our pilot data suggest that the country of origin does not strongly affect how pain is facially expressed or how facial responses are being scored. However, the type of cognitive impairment showed a clear effect in our pilot study, with elevated facial responses in individuals with intellectual disability.

High intensity interval training ameliorates cognitive impairment in T2DM mice possibly by improving PI3K/Akt/mTOR Signaling-regulated autophagy in the hippocampus

Exercise can improve cognitive impairment in type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are not clear, and the optimal exercise modes for cognitive benefits are controversial. The aim of this study was to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity interval training (MICT) on cognitive function and the PI3K/Akt/mTOR pathway as well as autophagy in T2DM mice. The results showed that 8 weeks of HIIT and MICT intervention could improve the spatial learning and memory ability of T2DM mice, as determined by the Morris water maze (MWM) test. Both HIIT and MICT similarly improved autophagy, as evidenced by increased Beclin1 and LC3 II/I ratios and decreased p62. Meanwhile, HIIT and MICT inhibited excessive activation of the PI3K/Akt/mTOR pathway in the hippocampus. HIIT induced a larger reduction in mTOR activity than MICT. This study suggests that both HIIT and MICT can alleviate cognitive decline induced by T2DM, improve autophagy in the hippocampus, and downregulate the excessive activation of the PI3K/Akt/mTOR signaling pathway, with similar effects.

Confident memory errors and disrupted reality testing in early psychosis

Schizophrenia is a psychiatric disorder characterized by a disruption in reality testing most often manifest in the form of delusions and hallucinations. Because determining the reality-basis of prior experiences is dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impaired reality testing. In the present study, we used an associative memory paradigm incorporating confidence ratings to examine whether patients with a recent onset of schizophrenia (n = 48) show a greater propensity for confident, yet incorrect responses during retrieval testing than healthy controls (n = 26) and whether such confident incorrect responses, specifically, are more strongly associated with positive symptoms than with negative symptoms. Using an analysis of variance design, we found that first-episode schizophrenia patients made a significantly greater number of confident errors than controls (i.e. they expressed high confidence in having seen pairs of items that were not paired at encoding and high confidence in having not seen pairs of items that were paired at encoding). We also found that the number of confident errors was specifically and differentially associated with positive symptom severity, to a significantly greater degree than with negative symptom severity and psychosocial functioning, and this association was not found between positive symptoms and uncertain responses, nor positive symptoms and overall task performance. These findings suggest that the propensity for incorrect memory judgements with high confidence, specifically, may be uniquely associated with disrupted reality testing and that this type of cognitive impairment is distinct from general deficits in memory and cognition in this respect.

Efficiency of donepezil in elderly patients undergoing orthopaedic surgery due to underlying post-operative cognitive dysfunction: study protocol for a multicentre randomised controlled trial

BackgroundPost-operative cognitive dysfunction (POCD) is an overarching term used to describe cognitive impairment identified in the preoperative or post-operative period. After surgical operations, older patients are particularly vulnerable to memory disturbances and other types of cognitive impairment. However, the pathogenesis of POCD remains unclear with no confirmed preventable or treatable strategy available. Our previous study demonstrated that the concentration of choline acetyl transferase in the cerebral spinal fluid was a predictive factor of POCD and that donepezil, which is an acetylcholinesterase inhibitor used in clinical settings for the treatment of Alzheimer’s disease, can prevent learning and memory impairment after anaesthesia/surgery in aged mice. This study aimed to determine the critical role of donepezil in preventing cognitive impairment in elderly patients undergoing orthopaedic surgery.MethodsA multicentre, double-blind, placebo-controlled, crossover clinical trial will be performed to assess the efficacy of donepezil in elderly patients undergoing orthopaedic surgery. Participants (n = 360) will receive donepezil (5 mg once daily) or placebo from 1 day prior to surgery until 5 days after surgery. Neuropsychological tests will be measured at 1 day before the operation and 1 week, 1 month, 6 months and 1 year after the operation.DiscussionThis research project mainly aimed to study the effects of donepezil in elderly patients undergoing orthopaedic surgery due to underlying POCD and to investigate the underlying physiological and neurobiological mechanisms of these effects. The results may provide important implications for the development of effective interfering strategies, specifically regarding cognitive dysfunction therapy using drugs.Trial registrationClinicalTrials.govNCT04423276. Registered on 14 June 2020

An unusual presentation of memory loss

Multiple system atrophy (MSA) is a neuro-degenerative disease, pathologically characterized by α-synuclein (αSyn)-immunopositive glial cytoplasmic inclusions (GCI). Compar ing to other synucleinopathies such as Parkinson's disease (PD) or Dementia with Lewy body (DLB), MSA has not been characterized by dementia. However, recent studies reported that various types of cognitive impairments could be presented in MSA.1 We report a case of MSA with severe cognitive impairment that proceeded 6 years before cerebellar dysfunctions of MSA.

Cognitive impairment in type 2 diabetes patients with and without diabetic peripheral neuropathy: a mismatch negativity study.

To assess the cognitive impairment in patients with type 2 diabetes mellitus (T2DM) using mismatch negativity (MMN) and to explore the relationship between cognitive impairment and diabetic peripheral neuropathy (DPN). Sixty-six T2DM patients and 40 healthy controls were included. For each participant, mini-mental state examination (MMSE) was applied to assess the general cognitive function and MMN was elicited. T2DM patients were divided into two subgroups: subgroup DPN-, patients without DPN; subgroup DPN+, patients with DPN. The MMSE scores, MMN amplitudes and latencies were compared between the T2DM group and the control group using univariate analysis of variance procedures, and also among the controls, subgroup DPN- and subgroup DPN+. Pearson's correlation coefficients (r) were used to analyze potential confounding clinical factors associated with MMN. T2DM patients had significantly lower MMSE scores compared with controls (23.25 ± 2.86 vs. 27.15 ± 1.83; P < 0.01), whereas those of the two subgroups were not significantly different. Both subgroup DPN+ and DPN- had longer latencies and lower amplitudes of MMN than the controls. The latencies of MMN were significantly longer in subgroup DPN+ compared with subgroup DPN-. The latency of MMN was positively correlated with the duration of the disease. Cognitive decline exists in patients with T2DM irrespective of the presence of DPN. Patients with DPN may have more severe cognitive dysfunction than those without DPN. MMN may be a promising tool for evaluating cognitive function.