Consequence of Dementia and Cognitive Impairment by Primary Nucleation Pathway.

An acquired loss of cognition in several cognitive domains that is severe enough to interfere with social or professional functioning is called dementia. As well as a moderately in-depth mental status examination by a clinician to identify impairments in memory, language, attention, visuospatial cognition, such as spatial orientation, executive function, and mood, the diagnosis of dementia requires a history evaluating for cognitive decline and impairment in daily activities, with confirmation from a close friend or family member. The start and organization of the cognitive assessment can be helped by short screening tests for cognitive impairment. Clinical presentations show that neurodegenerative diseases are often incurable because patients permanently lose some types of neurons. It has been determined through an assessment that, at best, our understanding of the underlying processes is still rudimentary, which presents exciting new targets for further study as well as the development of diagnostics and drugs. A growing body of research suggests that they also advance our knowledge of the processes that are probably crucial for maintaining the health and functionality of the brain. We concentrate on a number of the animal models of memory problems that have been mentioned in this review article because dementia has numerous etiologies. Serious neurological impairment and neuronal death are the main features of neurodegenerative illnesses, which are also extremely crippling ailments. The most prevalent neurodegenerative disorders are followed by those primary nucleation pathways responsible for cognitive impairment and dementia.

Peripheral Biomarkers in Manifest and Premanifest Huntington's Disease.

Huntington's disease (HD) is characterized by clinical motor impairment (e.g., involuntary movements, poor coordination, parkinsonism), cognitive deficits, and psychiatric symptoms. An inhered expansion of the CAG triplet in the huntingtin gene causing a pathogenic gain-of-function of the mutant huntingtin (mHTT) protein has been identified. In this review, we focus on known biomarkers (e.g., mHTT, neurofilament light chains) and on new biofluid biomarkers that can be quantified in plasma or peripheral blood mononuclear cells from mHTT carriers. Circulating biomarkers may fill current unmet needs in HD management: better stratification of patients amenable to etiologic treatment; the initiation of preventive treatment in premanifest HD; and the identification of peripheral pathogenic central nervous system cascades.

[Evaluation of the perspectives and experiences regarding lumbar puncture in cognitively impaired older adults over 70, their relatives and the care teams]. / Évaluation des représentations et du vécu liés à la ponction lombaire chez des patients âgés de plus de 70 ans atteints de troubles cognitifs, leurs accompagnants et les équipes soignantes.

INTRODUCTION: Lumbar puncture (LP) is an essential diagnostic procedure, which raises major concerns in older adults. Some patients may be denied LP because of the fear of complications in healthcare teams which are not familiar with the procedure. The objectives of our work were to analyze the perspectives and the experiences regarding scheduled LP in cognitively impaired older adults, as well as in their relatives, and the healthcare teams from geriatric day hospitals. METHODS: We conducted a qualitative, observational and multicentric study, based on semi-directive interviews of patients aged over 70 years with cognitive complaints undergoing a scheduled LP in a day hospital. Patients were interviewed before and after LP. Their relatives and the involved healthcare teams were also interviewed to analyze their expectations and perspectives regarding the procedure. The full interviews were transcribed and analyzed using interpretative phenomenological analysis. RESULTS: Ten patients (mean age 80.2 ± 7.2), five relatives and four healthcare teams were included. The goals and operating procedure of LP were poorly understood by several patients. Some individuals feared irreversible neurological consequences or LP-related pain, which was often overestimated with regards to the post-LP interviews. The patients' major expectation was to establish an accurate and early diagnosis of their cognitive disorder to provide optimal care plan. Relatives reported similar fears of major adverse events. They also expected an accurate diagnosis with biomarkers. The perspectives and experiences of the healthcare teams were heterogeneous, according to their level of practice of LP, but seemed in line with current scientific guidelines. CONCLUSION: This study highlighted the existence of false beliefs and poor knowledge regarding the LP procedure and its associated risks. The post-LP patients' feedbacks were better than their expectations, especially in day hospitals with solid experience in LP. Better patient information may be a key to improve our practice.

Nonlinear relationship between glycated hemoglobin and cognitive impairment after acute mild ischemic stroke.

BACKGROUND: Stroke is the second most common cause of morbidity and mortality. Even mild stroke survivors have an increased risk of cognitive impairment. Studies have been conducted on the relationship between glycated hemoglobin (HbA1c) and cognitive decline, but the findings have been inconsistent. Therefore, this study examined the link between HbA1c levels and cognitive impairment following acute mild ischemic stroke. METHODS: Data from 311 patients with acute mild ischemic stroke admitted to Suining Central Hospital, Sichuan Province, China, from January 1, 2015, to December 31, 2018, were evaluated. Fasting venous blood was taken to assess HbA1c levels on the day after admission. Cognitive function was assessed using the Chinese version of the Montreal Cognitive Assessment Scale (MoCA) 3-6 months after stroke onset. We used a generalized additive model and smooth curve fitting (penalty spline method) to assess the nonlinear relationship between HbA1c and poststroke cognitive impairment (PSCI). RESULTS: This study included 311 patients aged 23 to 96 years old (mean age: 67.37 ± 11.92 years), of whom 198 (63.67%) were men. Among the 311 stroke patients, 120 (38.59%) had PSCI. After adjusting for potential confounders, there was a nonlinear relationship between HbA1c and PSCI, with an inflection point of 8.2. To the left of the inflection point, the effect size, 95% confidence interval, and P value were 0.87, 0.58 to 1.31, and 0.5095, respectively; however, to the right of the inflection point, these numbers were 1.96, 1.08 to 3.58, and 0.0280. CONCLUSION: We found a nonlinear relationship between HbA1c and PSCI. When HbA1c was greater than 8.2%, HbA1c was positively correlated with PSCI.

Cognitive impairment after cancer treatment: mechanisms, clinical characterization, and management.

Cognitive impairment is a debilitating side effect experienced by patients with cancer treated with systemically administered anticancer therapies. With around 19.3 million new cases of cancer worldwide in 2020 and the five year survival rate growing from 50% in 1970 to 67% in 2013, an urgent need exists to understand enduring side effects with severe implications for quality of life. Whereas cognitive impairment associated with chemotherapy is recognized in patients with breast cancer, researchers have started to identify cognitive impairment associated with other treatments such as immune, endocrine, and targeted therapies only recently. The underlying mechanisms are diverse and therapy specific, so further evaluation is needed to develop effective therapeutic interventions. Drug and non-drug management strategies are emerging that target mechanistic pathways or the cognitive deficits themselves, but they need to be rigorously evaluated. Clinically, consistent use of objective diagnostic tools is necessary for accurate diagnosis and clinical characterization of cognitive impairment in patients treated with anticancer therapies. This should be supplemented with clinical guidelines that could be implemented in daily practice. This review summarizes the recent advances in the mechanisms, clinical characterization, and novel management strategies of cognitive impairment associated with treatment of non-central nervous system cancers.

Assessing causality in the association between neurocognitive gains and fasting.

Fasting is associated with improvements in cognitive function, and triggers weight loss in human and animal models. In recent years, the connection between fasting, brain health, and cognitive function has increasingly proven deserving of attention from researchers. The objective of this review work is to highlight evidence supporting a positive association between fasting and enhanced cognition. We looked at the following database sources "The Cochrane Library, PubMed, EMBASE, Web of Science and Google Scholar" for present review article. All the studies based on the key words "impact of fasting", or "cognitive function" or "brain stimulation". Much of this evidence demonstrates that fasting results in enhanced performance in cognitive tests of memory and visuospatial processing, which rely heavily on hippocampal function. The mechanisms responsible for the cognitive improvements associated with fasting are not fully understood, although current evidence suggests neuroplasticity plays an important role. Maintaining the health and the functionality of neurologically and cognitively impaired individuals can be extremely costly. Higher life expectancy and ageing populations globally is anticipated to increase the prevalence of many non-communicable, chronic, progressive conditions including neurological disorders.

Early auditory processing dysfunction in schizophrenia: Mechanisms and implications.

Schizophrenia is a major mental disorder that affects approximately 1% of the population worldwide. Cognitive deficits are a key feature of the disorder and a primary cause of long-term disability. Over the past decades, significant literature has accumulated demonstrating impairments in early auditory perceptual processes in schizophrenia. In this review, we first describe early auditory dysfunction in schizophrenia from both a behavioral and neurophysiological perspective and examine their interrelationship with both higher order cognitive constructs and social cognitive processes. Then, we provide insights into underlying pathological processes, especially in relationship to glutamatergic and N-methyl-D-aspartate receptor (NMDAR) dysfunction models. Finally, we discuss the utility of early auditory measures as both treatment targets for precision intervention and as translational biomarkers for etiological investigation. Altogether, this review points out the crucial role of early auditory deficits in the pathophysiology of schizophrenia, in addition to major implications for early intervention and auditory-targeted approaches.

Impact of COVID-19 infection on cognition and its association with neurological symptoms.

OBJECTIVE: To characterize the cognitive profile following COVID-19 infection and its possible association to clinical symptoms, emotional disturbance, biomarkers, and disease severity. METHODS: This was a single-center cross-sectional cohort study. Subjects between 20- and 60-year old with confirmed COVID-19 infection were included. Evaluation was performed between April 2020 and July 2021. Patients with previous cognitive impairment and other neurological or severe psychiatric disorders were excluded. Demographic and laboratory data were extracted from the medical records. RESULTS: Altogether 200 patients were included, 85 subjects were female (42.3%), and mean age was 49.12 years (SD: 7.84). Patients were classified into four groups: nonhospitalized (NH, n = 21), hospitalized without intensive care unit (ICU) nor oxygen therapy (HOSP, n = 42), hospitalized without ICU but with oxygen therapy (OXY, n = 107), and ICU (ICU, n = 31) patients. NH group was younger (p = .026). No significant differences were found in any test performed attending severity of illness (p > .05). A total of 55 patients reported subjective cognitive complaints (SCC). Subjects with neurological symptoms (NS) performed worse in trail making test B (p = .013), digits backwards (p = .006), letter&numbers (p = .002), symbol digit modalities test (p = .016), and Stroop color (p = .010) tests. CONCLUSIONS: OXY patients and females referred more SCC associated with symptoms of anxiety and depression. Objective cognitive performance was unrelated to SCC. No cognitive impairment was found regarding the severity of COVID-19 infection. Results suggest that NS such as headache, anosmia, and dysgeusia during infection were a risk factor for later cognitive deficits. Tests assessing attention, processing speed, and executive function were the most sensitive in detecting cognitive changes in these patients.

Vascular function and cognition in persons with multiple sclerosis: Preliminary examination.

BACKGROUND: Cognitive dysfunction is one of the most common consequences of multiple sclerosis (MS). Recent studies have noted a high incidence of vascular comorbidity that might be associated with cognitive decline among persons with MS. However, there is a lack of evidence on vascular biomarkers (e.g., arterial stiffness indices) that are associated with cognition in MS. The current study characterized differences in vascular function between persons with MS and healthy controls, and examined the association between vascular and cognitive function in persons with MS compared with healthy controls. RESULTS: The MS group had significantly worse cognitive performance and higher cfPWV than healthy controls. There were significant bivariate correlations between the Symbol Digit Modalities Test (SDMT) score with AIx75 (rs = -0.45) and cfPWV (rs = 0.30) in the MS sample, but not in healthy controls. Regression analyses further indicated a nonlinear association between cfPWV and the SDMT in the MS sample (p-values for ß coefficients < 0.05; adjusted R2 = 0.10). No significant associations were observed among other cognitive and vascular outcomes. CONCLUSION: Our findings suggest significant associations between arterial stiffness and cognitive processing speed in MS. This preliminary examination provides initial, cross-sectional support for future population-based research on cognitive and vascular function in persons with MS. Such results may be clinically important for developing interventions that focus on regulating vascular dysfunction as an early treatment for preventing cognitive impairment in the MS population.

Cognitive deficit in post-acute COVID-19: an opportunity for EEG evaluation?

BACKGROUND AND PURPOSE: Among the most common post-COVID symptoms, many patients experienced subjective cognitive deficit, commonly named "brain fog," that might be present also in those individuals without severe acute COVID-19 respiratory involvement. Some studies have investigated some of the mechanisms that might be associated with the brain fog with objective techniques including transcranial magnetic stimulation and neuroimaging. METHODS: The aim of this study was to investigate the presence of electroencephalographic (EEG) alterations in people with post-COVID self-reported cognitive deficit. RESULTS: Out of the 90 patients attending the post-COVID neurology ambulatory service, twenty patients presenting brain fog at least 4 weeks after acute non-severe COVID-19 infection, and without previous history of epilepsy, were investigated with 19-channel EEG, Montreal Cognitive Assessment (MoCA), and magnetic resonance imaging (MRI). EEG was found altered in 65% of the sample, among which 69% presented a slowing activity and 31% were characterized by epileptic discharges principally in the frontal areas. None of the patients showed DWI MRI lesions. CONCLUSIONS: These findings highlight the usefulness of EEG analysis to objectively describe possible neurophysiological abnormalities in post-COVID patients presenting subjective cognitive deficit.

Asymptomatic carotid stenosis and cognitive impairment.

INTRODUCTION: The aim of this review was to assess the evidence supporting an association between asymptomatic carotid stenosis (ACS) with impaired cognitive function due to chronic cerebral hypoperfusion and/or silent cerebral embolization. EVIDENCE ACQUISITION: PubMed/Medline, Embase and the Cochrane databases were searched up to December 1, 2022 to identify studies focusing on the association between ACS and cognitive function, as well as the mechanisms involved. EVIDENCE SYNTHESIS: A total of 49 studies were identified. The evidence supports an association between ACS and progressive cognitive deterioration. The mechanisms involved in the cognitive decline associated with ACS include cerebral hypoperfusion and silent cerebral embolization. Irrespective of the mechanism involved, severe ACS is associated with a progressive decline in several aspects of cognitive function, including global cognition, memory and executive function. CONCLUSIONS: Patients with ACS are at increased risk of developing a progressive decline in their cognitive function. The evidence from the present systematic review suggests that it may be inappropriate to consider ACS patients developing cognitive dysfunction as "asymptomatic". Besides stroke, myocardial infarction and death rates, future studies should include evaluation of cognitive function as part of their outcomes.

Egyptian adaptation and validation of the Edinburgh Cognitive and Behavioral Amyotrophic Lateral Sclerosis Screen (ECAS-EG).

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is the most common, fatal adult neuromuscular disease. It is a multi-system disorder characterized primarily by motor manifestations, but there is established evidence for cognitive and behavioral impairment, which is associated with poor prognosis, hence, the importance of tools for its assessment. The Edinburgh Cognitive and Behavioral Assessment Screen (ECAS) is an invaluable assessment tool for cognition in ALS-front temporal spectrum dementia (FTSD), as it accommodates physical challenges that usually confound traditional neuropsychological testing in those patients. OBJECTIVE AND METHODS: To validate the Egyptian Arabic version of ECAS (ECAS-EG) based on the original English scale. This is a prospective study. The ECAS was adapted and administered to 62 Egyptian ALS patients and 60 healthy controls. Patients were recruited from the Neuromuscular Unit, Ain Shams University Hospital. The ECAS was adapted to Egyptian Arabic after being translated using the back translation method. Internal consistency of the test, inter-rater reliability, and construct validity were assessed. RESULTS: The Egyptian Arabic version of ECAS (ECAS-EG) showed good internal consistency using Cronbach's alpha of 0.84. Inter-rater reliability was tested, values for all variables were compared, and no statistically significant differences were found (ICC = .997). ECAS-EG discriminated significantly between the patients from the control subjects (p-value of 0.001). There was a strong positive correlation between the ECAS-EG total score and the MoCA total score with a p-value of 0.001, thus indicating convergent validity. The test showed that 63% of Egyptian ALS patients were cognitively affected; most affected domains were executive functions and verbal fluency. CONCLUSION: The current study proves that the Egyptian version of the ECAS (ECAS-EG) is valid and reliable among Egyptian ALS patients and it would be applicable to the general Arabic-speaking population.

Patient-Centered Approaches to Cognitive Assessment in Acute TBI.

PURPOSE OF THE REVIEW: The purpose of this article is to help clinicians understand how underlying pathophysiologies and medical comorbidities associated with acute traumatic brain injury (TBI) can impact assessment of cognition during the initial stages of recovery. Clinicians can use information from this article to develop assessment plans rooted in patient-centered care. RECENT FINDINGS: The authors conducted a review of the literature related to the assessment of cognition in acute TBI, focusing on pathophysiology, medical comorbidities, and assessment approaches. Results indicated that TBI pathophysiologies associated with white and gray matter changes make many patients vulnerable to cognitive deficits. Acute comorbidities such as psychological and pain status influence cognitive abilities as well. The current approaches to cognitive assessment can be limited in many ways, though by using the patient's neuropathological profile, noted comorbidities, and other patient specific factors, clinicians can potentially improve the effectiveness of assessment.

Functional cognitive disorders: clinical presentations and treatment approaches.

Functional cognitive disorders (FCDs) are a common cause of subjective and mild cognitive impairment. Isolated FCDs commonly present to the cognitive clinic, but examination of the nature of the symptoms suggests that they can also be understood as a transdiagnostic feature of many other conditions. This article examines methods of formulating the cognitive difficulties in order to identify treatment targets in people with FCDs.

Assessing Depression and Cognitive Impairment Following Stroke and Neurotrauma: Behavioral Methods for Quantifying Impairment and Functional Recovery.

Rodent models of stroke and neural injury are reliable and useful tools for testing new interventions and therapeutics. In addition to physical (motor) impairment, cognitive deficits and depressive behaviors are often observed due to neurotrauma. Proper experimental design of pre- and post-assessments of these behaviors that reduce or minimize the confounding effects of motor impairment are essential for determining markers of progression of impairment or recovery. This chapter provides step-by-step laboratory protocols for assessing cognition using the Barnes maze and the novel object recognition test (NORT) and depressive-like behaviors using the sucrose preference test, the three-chambered sociability approach test, and the burrowing test.

The Association Between Diabetes Duration and Domain-Specific Cognitive Impairment: A Population-Based Study.

BACKGROUND: Diabetes is a risk factor for cognitive impairment, and disease duration is associated with geriatric decline and functional disabilities. OBJECTIVE: This study aimed to examine the association of diabetes duration with domain-specific cognitive impairment in elderly. METHODS: A total of 3,142 participants from the National Health and Nutrition Examination Survey (NHANES) from the period between 2011 and 2014 were included. We assessed cognitive function using the Digit Symbol Substitution Test (DSST), the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test and animal fluency (AF) test. RESULTS: After adjusting for age, sex, race/ethnicity, education level, and annual household income, we found that diabetes with a duration longer than 20 years were at 3.32-fold increased risk of DSST impairment (OR = 3.32, 95% CI: 1.95 to 5.67), 1.72-fold increased risk of CERAD-WL impairment (OR = 1.72, 95% CI: 1.13 to 2.62), and 1.76-fold increased risk of AF impairment (OR = 1.76, 95% CI: 1.23 to 2.53), compared with those with no diabetes. Associations were generally stronger in women than in men. Participants with diabetes, who were diagnosed at 50-59 years old were at increased risk of DSST impairment, CERAD-WL impairment, CERAD-DR impairment, and AF impairment per 5 years longer duration of diabetes. CONCLUSION: Longer diabetes duration was associated with the increased risk of cognitive impairment, especially in processing speed and attention. The presence of chronic kidney disease was associated with the increased risk of DSST impairment.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part IV: Cognitive-Communication and Social Cognition Disorders.

INTRODUCTION: Moderate to severe traumatic brain injury causes significant cognitive impairments, including impairments in social cognition, the ability to recognize others' emotions, and infer others' thoughts. These cognitive impairments can have profound negative effects on communication functions, resulting in a cognitive-communication disorder. Cognitive-communication disorders can significantly limit a person's ability to socialize, work, and study, and thus are critical targets for intervention. This article presents the updated INCOG 2.0 recommendations for management of cognitive-communication disorders. As social cognition is central to cognitive-communication disorders, this update includes interventions for social cognition. METHODS: An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for interventions for cognitive-communication and social cognition disorders, a decision-making algorithm tool, and an audit tool for review of clinical practice. RESULTS: Since INCOG 2014, there has been significant growth in cognitive-communication interventions and emergence of social cognition rehabilitation research. INCOG 2.0 has 9 recommendations, including 5 updated INCOG 2014 recommendations, and 4 new recommendations addressing cultural competence training, group interventions, telerehabilitation, and management of social cognition disorders. Cognitive-communication disorders should be individualized, goal- and outcome-oriented, and appropriate to the context in which the person lives and incorporate social communication and communication partner training. Group therapy and telerehabilitation are recommended to improve social communication. Augmentative and alternative communication (AAC) should be offered to the person with severe communication disability and their communication partners should also be trained to interact using AAC. Social cognition should be assessed and treated, with a focus on personally relevant contexts and outcomes. CONCLUSIONS: The INCOG 2.0 recommendations reflect new evidence for treatment of cognitive-communication disorders, particularly social interactions, communication partner training, group treatments to improve social communication, and telehealth delivery. Evidence is emerging for the rehabilitation of social cognition; however, the impact on participation outcomes needs further research.

Within-individual variability in cognitive performance in schizophrenia: A narrative review of the key literature and proposed research agenda.

Schizophrenia is a neurodevelopmental disorder and a leading cause of disability worldwide. Deficits in cognitive function are characteristic of schizophrenia and are predictors of functional outcomes in the disorder. Within-individual variability (WIV) in cognitive performance is elevated in schizophrenia and has been suggested to provide additional insight into cognitive function over and above mean performance measures. Despite growing interest in WIV in schizophrenia, research on the clinical significance and neural correlates of WIV in the disorder remains sparse. The present narrative review summarizes the key literature linking WIV in schizophrenia to clinical, neural, and genetic correlates. Here, we aim to highlight key knowledge gaps and provide directions for future research into WIV in schizophrenia.

Sensitivity of conventional cognitive tests in multiple sclerosis: Application of item response theory.

BACKGROUND: Cognitive impairment (CI) is common in Multiple Sclerosis (MS), and its prevalence rate ranges between 22% and 70%. Because CI significantly impacts vocational status, caregiver burden, and quality of life, an accurate neuropsychological assessment is required. Three widely used and validated batteries for MS-associated CI are the Brief Repeatable Neuropsychological Battery (BRN-B), the Minimal Assessment of Cognitive Function (MACFIMS), and the Brief International Cognitive Assessment (BICAMS). Although similar, these batteries differ in time-consuming and in specific tests employed. This study aims to assess the sensitivity of cognitive tests included in these batteries through an Item Response Theory approach. METHODS: Ninety-seven patients with MS and 91 demographically matched controls (HC) were consecutively assessed using the three neuropsychological batteries (i.e., BRN-B, MACFIMS, and BICAMS). Continuous Response Model (CRM) was used to identify the cognitive test(s) that best discriminate patients with MS from HC. Receiver Operating Characteristic (ROC) curve analysis was used to determine the accuracy of the CRM results. RESULTS: Cognitive tests loaded on two different latent variables: the 'higher-order executive functioning,' consisting of tests assessing concept formation, problem-solving, and inhibitory control, and the 'memory and information processing speed,' comprising tests assessing long-term, working memory, and information processing speed. The Delis Kaplan Executive Functioning System-Sorting Test and the Stroop Test were the most sensitive tests in differentiating cognitive functioning between MS and HC. CONCLUSIONS: This study confirms the importance of including a more extensive executive assessment in MS clinical practice since higher-order executive functions (e.g., abstraction and inhibitory control) significantly impact patients' quality of life and functional autonomy. Clinical implications of careful dissection of executive functioning in MS neuropsychological assessment are discussed.