Analysis of changes in social isolation, loneliness, or both, and subsequent cognitive function among older adults: Findings from a nationwide cohort study.

INTRODUCTION: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function. METHODS: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed. RESULTS: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05). DISCUSSION: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment. HIGHLIGHTS: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.

Development and validation of a nomogram predictive model for cognitive impairment in cerebral small vessel disease: a comprehensive retrospective analysis.

Background: Cerebral small vessel disease (CSVD) is a common neurodegenerative condition in the elderly, closely associated with cognitive impairment. Early identification of individuals with CSVD who are at a higher risk of developing cognitive impairment is crucial for timely intervention and improving patient outcomes. Objective: The aim of this study is to construct a predictive model utilizing LASSO regression and binary logistic regression, with the objective of precisely forecasting the risk of cognitive impairment in patients with CSVD. Methods: The study utilized LASSO regression for feature selection and logistic regression for model construction in a cohort of CSVD patients. The model's validity was assessed through calibration curves and decision curve analysis (DCA). Results: A nomogram was developed to predict cognitive impairment, incorporating hypertension, CSVD burden, apolipoprotein A1 (ApoA1) levels, and age. The model exhibited high accuracy with AUC values of 0.866 and 0.852 for the training and validation sets, respectively. Calibration curves confirmed the model's reliability, and DCA highlighted its clinical utility. The model's sensitivity and specificity were 75.3 and 79.7% for the training set, and 76.9 and 74.0% for the validation set. Conclusion: This study successfully demonstrates the application of machine learning in developing a reliable predictive model for cognitive impairment in CSVD. The model's high accuracy and robust predictive capability provide a crucial tool for the early detection and intervention of cognitive impairment in patients with CSVD, potentially improving outcomes for this specific condition.

From the Intensive Care Unit to Recovery: Managing Post-intensive Care Syndrome in Critically Ill Patients.

Post-intensive care syndrome (PICS) is the term used to describe the decline in the physical, cognitive, and/or mental condition of individuals who have been discharged from the intensive care unit (ICU). This complication could result in a significant reduction in quality of life, with some patients experiencing symptoms of prolonged weakness, depression, anxiety, and post-traumatic stress disorder (PTSD). Intensive care advancement over the years has resulted in an increase in ICU survival rates and a proportional increase in PICS, creating a need for more in-depth research into the prevention and management of the disease. Hence, this study aims to examine the present body of literature on PICS, encompassing its underlying physiological processes and elements that contribute to its development, methods for evaluating and diagnosing the condition, current treatment choices as well as potential new approaches, and the constraints in managing PICS and the necessity for further investigation. In this article, studies were compiled from several databases, including, but not limited to, Google Scholar, PubMed, and Cochrane Library. These studies were reviewed, and their data were used to highlight important aspects regarding the efficacy of current PICS screening tools, the optimization and limitations of both pharmacologic and non-pharmacologic treatment methods, and the feasibility and safety of emerging treatments and technologies. The major conclusions of this review were centered around the need for multidisciplinary management of PICS. From pharmacological management using analgesia to non-pharmacological management using early mobilization and exercise therapy, the effective treatment of PICS requires a multifaceted approach. Patient follow-up and its importance were touched upon, including strategies and policies to bolster proper follow-up, thereby increasing favorable outcomes. Lastly, the importance of family involvement and the increased need for research into this topic were highlighted.

A 2-Year Longitudinal Randomized Control Trial of Speed of Processing Cognitive Training in Aging Adults with HIV-Associated Neurocognitive Disorder: Results of the Think Fast Study.

Nearly 40% of people with HIV (PWH) experience HIV-associated Neurocognitive Disorder (HAND). In this 3-group efficacy study, 216 PWH 40 + years with HAND or borderline HAND were randomized to either: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73), or (3) 10 h of Internet navigation training (n = 73; contact control group). Participants were administered a measure of SOP [i.e., the Useful Field of View Test (UFOV®)] at baseline, at posttest immediately after training, and at year 1 and year 2 follow up. Intent-to-treat linear mixed-effect models with subject-specific intercept and slope were fitted to estimate between-group mean differences at the follow-up time-points. At the post-intervention time-point, small beneficial SOP training effects were observed for the 10-h group in UFOV® total (d = 0.28, p = 0.002). Effects were of larger magnitude for the 20-h group in these same outcomes [UFOV® total (d = 0.43, p < 0.001)]. These results indicated better benefit with more training. No intervention effect was observed at year 1. At year 2, beneficial effects of small magnitude were observed again in the 10-h group [UFOV® total (d = 0.22, p = 0.253)] with larger small-to-moderate magnitude in the 20-h group [UFOV® total (d = 0.32, p = 0.104)]. This study suggests that SOP training can improve a key indicator of this cognitive performance and that treatment gains are small-to-moderate over a two-year period. Prior literature suggests slower SOP is predictive of impairment in everyday functioning in older PWH; such an approach could potentially improve everyday functioning in PWH.

Cerca del 40% de las personas viviendo con VIH (PVV) experimentan Trastorno Neurocognitivo Asociado al VIH (HAND, por sus siglas en inglés). En este estudio de eficacia de 3 grupos, se aleatorizó a 216 PVV mayores de 40 años de edad con HAND o HAND límite a: (1) 10 horas de entrenamiento en velocidad de procesamiento (SOP, por sus siglas en inglés) (n = 70); (2) 20 horas de entrenamiento SOP (n = 73), o (3) 10 horas de entrenamiento en navegación por Internet (n = 73; grupo control de contacto). Se administró una medida de SOP a los participantes [la Prueba de Campo de Visión Útil (UFOV®)] al inicio, inmediatamente después del entrenamiento, y en el seguimiento de año 1 y año 2. Los datos se analizaron bajo el principio de intención de tratar, utilizando modelos lineales de efectos mixtos para estimar las diferencias promedio entre grupos en los puntos de seguimiento. En el punto de tiempo de post- entrenamiento, se observaron pequeños efectos beneficiosos del entrenamiento SOP para el grupo de 10 horas en el puntaje total de UFOV® (d = 0.28, p = 0.002). Para esta misma medida, los efectos fueron de mayor magnitud en el grupo de 20 horas [UFOV® total (d = 0.43, p < 0.001)]. Estos resultados indicaron un mayor beneficio con más entrenamiento. No se observó ningún efecto de intervención en el año 1. En el año 2, se observaron efectos beneficiosos de pequeña magnitud nuevamente en el grupo de 10 horas [UFOV® total (d = 0.22, p = 0.253)] y en el grupo de 20 horas [UFOV® total (d = 0.32, p = 0.104)] con una magnitud pequeña a moderada). Este estudio confirma que el entrenamiento SOP puede mejorar un indicador clave de este rendimiento cognitivo y que las ganancias del tratamiento son pequeñas a moderadas durante un período de dos años. La literatura previa sugiere que una SOP más lenta es predictiva de deterioro en el funcionamiento diario en PVV mayores; tal enfoque podría mejorar potencialmente el funcionamiento diario en PVV.

Cognitive impairment in people living with HIV: mechanisms, controversies, and future perspectives.

Despite the dramatic decrease in HIV-associated neurocognitive impairment (NCI) in the combined antiretroviral treatment (cART) era, subtler neuropsychological complications remain prevalent. In this review, we discuss the changing pathophysiology of HIV-associated NCI, considering recent evidence of HIV neuropathogenesis, and the pivotal role of cART. Furthermore, we address the multifactorial nature of NCI in people living with HIV, including legacy and ongoing insults to the brain, as well as host-specific factors. We also summarize the ongoing debate about the refinement of diagnostic criteria, exploring the strengths and limitations of these recent approaches. Finally, we present current research in NCI management in people living with HIV and highlight the need for using both pharmacological and nonpharmacological pathways toward a holistic approach.

Temporal dynamics of depressive symptoms and cognitive decline in the oldest old: dynamic time warp analysis of the Leiden 85-plus study.

BACKGROUND: The prevalence of depressive symptoms and cognitive decline increases with age. We investigated their temporal dynamics in individuals aged 85 and older across a 5-year follow-up period. METHODS: Participants were selected from the Leiden 85-plus study and were eligible if at least three follow-up measurements were available (325 of 599 participants). Depressive symptoms were assessed at baseline and at yearly assessments during a follow-up period of up to 5 years, using the 15-item Geriatric Depression Scale (GDS-15). Cognitive decline was measured through various tests, including the Mini Mental State Exam, Stroop test, Letter Digit Coding test and immediate and delayed recall. A novel method, dynamic time warping analysis, was employed to model their temporal dynamics within individuals, in undirected and directed time-lag analyses, to ascertain whether depressive symptoms precede cognitive decline in group-level aggregated results or vice versa. RESULTS: The 325 participants were all 85 years of age at baseline; 68% were female, and 45% received intermediate to higher education. Depressive symptoms and cognitive functioning significantly covaried in time, and directed analyses showed that depressive symptoms preceded most of the constituents of cognitive impairment in the oldest old. Of the GDS-15 symptoms, those with the strongest outstrength, indicating changes in these symptoms preceded subsequent changes in other symptoms, were worthlessness, hopelessness, low happiness, dropping activities/interests, and low satisfaction with life (all P's < 0.01). CONCLUSION: Depressive symptoms preceded cognitive impairment in a population based sample of the oldest old.

Patient Outcomes and Management Strategies for Intensive Care Unit (ICU)-Associated Delirium: A Literature Review.

Delirium is a significant public health concern, with tremendous implications for patient outcomes. Intensive care unit (ICU)-related delirium is gaining attention due to the higher prevalence of delirium in ICU-admitted patients. The most common negative outcomes of ICU delirium include cognitive impairments, functional dependence, high incidence of mortality, extended stay in the ICU, and high costs. So far, no single etiological factor has been identified as the sole cause of delirium. Several functional, neurotransmitter, or injury-causing hypotheses have been proposed for ICU delirium. Several risk factors contribute to the development of delirium in patients admitted to the ICU. These are age, gender, types of sedation, physical restraints, medical and surgical interventions, pain, and extended stay in the ICU. The most commonly used assessment modules for ICU delirium are the PREdiction of DELIRium in ICu patients (PRE-DELIRIC), Early PREdiction model for DELIRium in ICu patients (E-PRE-DELERIC), and Lanzhou Model, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Intensive Care Delirium Screening Checklist (ICDSC), and Delirium Rating Scale (DRS). There is no proper treatment for ICU delirium; however, it can be managed through various pharmacological and non-pharmacological interventions. Healthcare providers should receive constant education and training on delirium recognition, prevention, and management to enhance patient care and outcomes in the ICU. Further research is needed on the effective prevention and management of ICU delirium.

Mild cognitive impairment and microbiota: what is known and future perspectives.

Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition, there is a recent growing interest in the identification of non-invasive markers able to predict the progression from MCI to a more advanced stage of the disease. Previous evidence showed the close link between gut microbiota and neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Conversely, the actual relationship between gut microbiota and MCI is yet to be clarified. In this work, we provide an overview about the current knowledge regarding the role of gut microbiota in the context of MCI, also assessing the potential for microbiota-targeted therapies. Through the review of the most recent studies focusing on this topic, we found evidence of an increase of Bacteroidetes at phylum level and Bacteroides at genus level in MCI subjects with respect to healthy controls and patients with AD. Despite such initial evidence, the definitive identification of a typical microbiota profile associated with MCI is still far from being achieved. These preliminary results, however, are growingly encouraging research on the role of gut microbiota modulation in improving the cognitive status of pre-dementia subjects. To date, few studies evaluated the role of probiotics in MCI subjects, and they showed favorable results, although still biased by small sample size, heterogeneity of study design and short follow-up.

Factors associated with cancer-related cognitive impairment in patients with lung cancer: A systematic review.

PURPOSE: Cognitive impairment is common in lung cancer patients and impacts their quality of life. Little is known about the etiology of cognitive impairment in lung cancer patients. However, the associated factors of cognitive impairment among lung cancer patients have not been systematically reviewed. This review aimed to summarize the factors related to cognitive impairment among lung cancer patients. METHODS: PubMed, EMBASE, PsycINFO, CINAHL Plus, and Web of Science were searched to retrieve articles published from data inception until January 21, 2024, focusing on factors associated with cognitive impairment among lung cancer patients. Critical appraisal was undertaken by two reviewers independently using the Newcastle-Ottawa Scale. RESULTS: A total of 17 observational studies were included. The results showed that 20 factors are associated with cognitive impairment, including psychological factors (loneliness, fatigue, anxiety, depression, high symptom burden, and baseline cognitive impairment), lifestyle and functional factors (daily step counts, smoking, and activities of daily living or instrumental activities of daily living impairments), medical treatment factors (cranial irradiation, chemotherapy, lobar resection, postoperative delirium, and on medication), and neuroimmunological factors (have neuronal autoantibodies, altered Default Mode Network connectivity, dysregulation in glutamate and glutamate metabolism, mitochondrial dysfunction, blood-brain barrier leakage, and reduced T-lymphocytes). CONCLUSION: This is the first study to systematically review 20 factors associated with cognitive impairment among lung cancer patients, encompassing psychology, lifestyle and functional, medical treatment, and neuroimmunological factors. These findings can help clinicians identify at-risk patients and develop evidence-based interventions to prevent cognitive impairment among lung cancer patients.

The remarkable impact of Opuntia Ficus Indica fruit administration on metabolic syndrome: Correlations between cognitive functions, oxidative stress and lipid dysmetabolism in the high-fat, diet-fed rat model.

BACKGROUND: A wealth of evidence underscores the bioactive properties of nutraceuticals and functional foods in addressing oxyinflammatory-based diseases with implications at both peripheral and central levels. Opuntia ficus-indica (OFI) is well-documented for its health-promoting attributes, though its fruit (OFIF) remains relatively understudied. Not only poses Metabolic Syndrome (MetS) cardiometabolic risks but also contributes significantly to cognitive impairment, especially in crucial brain areas such as hippocampus and hypothalamus. METHODS: Following 8 weeks of HFD to induce MetS, rats received OFIF oral supplementation for 4 weeks to evaluate cognitive and affective modifications using behavioural paradigms, i.e. open field, burrowing, white-dark box, novelty-suppressed feeding, and object recognition tests. Our investigation extended to biochemical evaluations of lipid homeostasis, central and peripheral oxidative stress and neurotrophic pathways, correlating these measures together with circulating leptin levels. RESULTS: Our data revealed that OFIF modulation of leptin positively correlates with systemic and brain oxidative stress, with markers of increased anxiety-like behaviour and impaired lipid homeostasis. On the other hand, leptin levels reduced by OFIF are associated with improved antioxidant barriers, declarative memory and neurotrophic signalling. DISCUSSION: This study underscores OFIF neuroactive potential in the context of MetS-associated cognitive impairment, offering insights into its mechanisms and implications for future therapeutic strategies.

A Clinical Neurological Approach to the Child With Adenosine Deaminase Deficiency.

BACKGROUND: Severe combined immunodeficiency secondary to adenosine deaminase deficiency is rare. The deficiency of this enzyme results in the accumulation of substrates in the tissues, including the brain. Clinical signs of neurological involvement may include seizures, neurodevelopmental disorders, hypotonia, and sensorineural hearing loss. Hematopoietic stem cell transplantation corrects the failure of the immune system but not the neurological involvement. OBJECTIVES: To describe the spectrum of neurological complications identified in a series of children with severe combined immunodeficiency due to adenosine deaminase deficiency. Additionally, we propose a neurological approach including electrophysiological, radiological, and neurocognitive studies to address this group of children in an efficient and timely manner. METHODS: A descriptive, observational, retro-, and prospective analysis of patients with a confirmed immunological diagnosis seen between 1996 and 2021 and referred to the Department of Neurology for neurological evaluation was conducted. RESULTS: Ten patients met the inclusion criteria. The median age at diagnosis was 4 months (range, 1-36 months). All patients had neurodevelopmental delay with hypotonia in six, language delay in three, sensorineural hearing loss in four, and spastic paraparesis in one patient. Two children developed an epileptic syndrome, consisting of generalized epilepsy in one and focal epilepsy in the other. Neuroimaging showed brain calcifications in the basal ganglia and/or centrum semiovale in four patients and enlarged subarachnoid spaces in two other patients. CONCLUSION: In this pediatric series, the rate of neurological involvement associated with abnormalities on neuroimaging was high. Although this involvement could be related to accumulation of adenosine metabolites in the central nervous system, the possibility of associated chronic infections should be ruled out. Given the neurological manifestations, it is important to involve the pediatric neurologist in the multidisciplinary follow-up team.

Brachial-Ankle Pulse Wave Velocity is Associated with Incident Dementia in Patients with Cerebral Small-Vessel Disease.

AIMS: Increased arterial stiffness is associated with the severity of cerebral small-vessel disease (SVD) and may predict incident dementia. This study investigated the predictive value of brachial-ankle pulse wave velocity (ba-PWV) for dementia and cognitive decline. METHODS: Data were obtained from a Japanese cohort of 478 patients who underwent ba-PWV measurement. Magnetic resonance imaging (MRI) was used to evaluate SVD severity. The Mini-Mental State Examination (MMSE) and the Japanese version of the Montreal Cognitive Assessment (MoCA-J) were used to assess the cognitive function. The primary outcome was the incidence of dementia. The secondary outcome was cognitive change during three years of follow-up. RESULTS: The median age was 71 years old, 61% were men, and the median ba-PWV was 1787 cm/s. Dementia was diagnosed in 23 patients during a mean follow-up of 4.8 years. A Cox proportional hazard regression analysis revealed that the highest quartile (ba-PWV ≥ 2102 cm/s) was associated with a significantly higher risk of dementia than the first to third quartiles (ba-PWV ≤ 2099 cm/s) after adjusting for risk factors, the mean blood pressure, the MoCA-J score, and SVD severity (adjusted HR, 3.40; 95% CI, 1.24-9.34; P=0.018). Longitudinal cognitive changes in 192 patients indicated that ba-PWV was negatively related to changes in the MoCA-J score (r=-0.184, P=0.011). The decline in the MoCA-J score in the highest quartile was greater than that in the first to third quartiles after adjusting for risk factors, SVD severity, and baseline MoCA-J score (P=0.017). CONCLUSIONS: ba-PWV was associated with incident dementia and cognitive decline, independent of age, risk factors, the baseline cognitive function, and the SVD severity.

Cancer-related cognitive impairment in older adults with acute myeloid leukemia treated with hypomethylating agents and venetoclax chemotherapy: a longitudinal descriptive study.

PURPOSE: To explore cancer-related cognitive impairment (CRCI) in older adults with acute myeloid leukemia (AML) receiving venetoclax in combination with hypomethylating agents or low-dose cytarabine chemotherapy. METHODS: This study is a longitudinal, qualitative descriptive study. Participants were recruited using purposive sampling. Semi-structured interviews were conducted among 11 older adults with AML at cycle 2, cycle 4, and cycle 7 of chemotherapy. An early end-of-study interview was conducted for those who changed treatment plans during the study follow-up. RESULTS: A total of 22 transcripts were included for thematic analysis. Four themes emerged: (1) CRCI experiences, (2) impact of CRCI, (3) CRCI coping strategies, and (4) perceived CRCI-related factors. Older adults with AML experienced challenges in memory, language, and attention both intermittently and daily. These cognitive changes impacted their emotion, daily activities, social connection, and their caregivers' responsibilities. Hence, these older adults with AML developed problem-solving and emotional coping strategies to cope with CRCI. Older adults with AML also identified demographic, physiology/clinical, psychological, and other factors that might contribute to CRCI. CONCLUSION: This study offers important insight for clinicians to understand how older adults with AML experience CRCI and how it impacts their daily routines. It indicates that clinicians should ask patients about their experience with cognitive changes at each encounter to provide support or coping strategies as needed to prevent CRCI from further hindering their quality of life.

Correlation between lipoprotein-associated phospholipase A2 and poststroke mild cognitive impairment.

OBJECTIVES: This study aimed to investigate the correlation between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) and poststroke mild cognitive impairment (PSMCI). METHODS: The patients included in the study were divided into PSMCI (68 cases) and cognitively normal (CN) (218 cases) groups and followed up for six months. Demographic and clinical data were collected. A logistic regression analysis was performed to determine whether Lp-PLA2 is an independent risk factor for PSMCI. Spearman's correlation analysis was used to examine the correlation between Lp-PLA2 levels and Montreal Cognitive Assessment (MoCA) scores. A receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic threshold value of Lp-PLA2 for PSMCI. RESULTS: Serum Lp-PLA2 levels were significantly higher in the PSMCI group than in the CN group. The logistic regression analysis showed that Lp-PLA2 was an independent risk factor for PSMCI (OR = 1.05, 95% CI = 1.03-1.07). Spearman's correlation analysis revealed a significant correlation between the Lp-PLA2 levels and MoCA scores (R = -0.49). The area under the ROC curve for Lp-PLA2 was 0.849, and the threshold value for PSMCI occurrence was 236.8 ng/ml. CONCLUSIONS: Elevated serum Lp-PLA2 is an independent risk factor for PSMCI and may serve as a potential biomarker for PSMCI.

Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. HIGHLIGHTS: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.

Nanoscale flow cytometry-based quantification of blood-based extracellular vesicle biomarkers distinguishes MCI and Alzheimer's disease.

INTRODUCTION: Accurate testing for Alzheimer's disease (AD) represents a crucial step for therapeutic advancement. Currently, tests are expensive and require invasive sampling or radiation exposure. METHODS: We developed a nanoscale flow cytometry (nFC)-based assay of extracellular vesicles (EVs) to screen biomarkers in plasma from mild cognitive impairment (MCI), AD, or controls. RESULTS: Circulating amyloid beta (Aß), tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, p-tauS235, ubiquitin, and lysosomal-associated membrane protein 1-positive EVs distinguished AD samples. p-tau181, p-tau217, p-tauS235, and ubiquitin-positive EVs distinguished MCI samples. The most sensitive marker for AD distinction was p-tau231, with an area under the receiver operating characteristic curve (AUC) of 0.96 (sensitivity 0.95/specificity 1.0) improving to an AUC of 0.989 when combined with p-tauS235. DISCUSSION: This nFC-based assay accurately distinguishes MCI and AD plasma without EV isolation, offering a rapid approach requiring minute sample volumes. Incorporating nFC-based measurements in larger populations and comparison to "gold standard" biomarkers is an exciting next step for developing AD diagnostic tools. HIGHLIGHTS: Extracellular vesicles represent promising biomarkers of Alzheimer's disease (AD) that can be measured in the peripheral circulation. This study demonstrates the utility of nanoscale flow cytometry for the measurement of circulating extracellular vesicles (EVs) in AD blood samples. Multiple markers including amyloid beta, tau, phosphorylated tau (p-tau)181, p-tau231, p-tau217, and p-tauS235 accurately distinguished AD samples from healthy controls. Future studies should expand blood and cerebrospinal fluid-based EV biomarker development using nanoflow cytometry approaches.

Role of Metalloproteinases in Diabetes-associated Mild Cognitive Impairment.

Diabetes has been linked to an increased risk of mild cognitive impairment (MCI), a condition characterized by a subtle cognitive decline that may precede the development of dementia. The underlying mechanisms connecting diabetes and MCI involve complex interactions between metabolic dysregulation, inflammation, and neurodegeneration. A critical mechanism implicated in diabetes and MCI is the activation of inflammatory pathways. Chronic low-grade inflammation, as observed in diabetes, can lead to the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), and interferon-gamma (IFNγ), each of which can exacerbate neuroinflammation and contribute to cognitive decline. A crucial enzyme involved in regulating inflammation is ADAM17, a disintegrin, and metalloproteinase, which can cleave and release TNF-α from its membrane-bound precursor and cause it to become activated. These processes, in turn, activate additional inflammation-related pathways, such as AKT, NF-κB, NLP3, MAPK, and JAK-STAT pathways. Recent research has provided novel insights into the role of ADAM17 in diabetes and neurodegenerative diseases. ADAM17 is upregulated in both diabetes and Alzheimer's disease, suggesting a shared mechanism and implicating inflammation as a possible contributor to much broader forms of pathology and pointing to a possible link between inflammation and the emergence of MCI. This review provides an overview of the different roles of ADAM17 in diabetes-associated mild cognitive impairment diseases. It identifies mechanistic connections through which ADAM17 and associated pathways may influence the emergence of mild cognitive impairment.

Association Between the Average Number of In-Network Hospitals and Medical Counseling for Cognitive Impairment in South Korea.

OBJECTIVES: Mild cognitive impairment, a pressing concern in the face of a rapidly growing global older adult population, necessitates effective management strategies focused on sustained symptom relief and preventing deterioration. Community Dementia Care Centers, in partnership with in-network hospitals, aim to provide support for preventing mild cognitive impairment and dementia. Medical counseling, influenced by in-network hospitals, is crucial for tailoring interventions to the cognitive abilities and specific needs of each older adult, protecting against dementia. Disparities in the number of in-network hospitals and healthcare infrastructure can contribute to uneven access to dementia care, thereby creating health inequities. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Using data from the Korea Community Health Survey (2018-2019), this study focused on South Korean individuals aged 60 and older in 17 metropolitan areas and provinces. METHODS: A multiple regression analysis was used to examine the relationship between the average number of in-network hospitals and medical counseling experience, considering sociodemographic factors and related variables. RESULTS: Areas with a higher average number of in-network hospitals exhibited increased medical counseling experiences. Significantly higher odds for medical counseling experience were observed in regions with "more than 5 hospitals" (1.36; 95% CI, 1.20-1.54; P = .000) than those with "3 or fewer hospitals." CONCLUSIONS AND IMPLICATIONS: This study underscores the importance of infrastructure, particularly collaborative hospitals that support Community Dementia Care Centers, in influencing individual dementia management and prevention. These findings highlight the significance of dementia prevention and management infrastructures, emphasizing the need for practical assistance, particularly in regions crucial for achieving health equity.

Effectiveness of a mobile application for independent computerized cognitive training in patients with mild cognitive impairment: study protocol for the NeNaE Study, a randomized controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals' quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention ("NeuroNation MED") in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. METHODS: This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT ("NeuroNation MED") for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. DISCUSSION: This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.

Obstructive Sleep Apnea Among Patients with Mild Cognitive Impairment.

Background: Obstructive sleep apnea (OSA) is associated with cognitive disorders, but little is known about prevalence of co-occurring OSA and mild cognitive impairment (MCI) as well as about co-occurring OSA and Alzheimer's disease (AD). Pathophysiological models integrating OSA, cognitive deficits and neurodegeneration remain speculative. Findings in this area could contribute to the knowledge about pathophysiological processes in cognitive disorders and neurodegenerative processes, be helpful for the diagnosis of cognitive disorders and provide approaches for the treatment of cognitive disorders. Objective: Examining the prevalence of OSA and patterns of cognitive deficits as well as AD biomarker profiles associated with OSA in a cohort of 104 MCI patients. Methods: Assessments used include: respiratory polygraphy, The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery (CERAD NB), Tau, phosphoTau181, amyloid-ß-1-42/1-40, 18F-fluorodeoxyglucose positron emission tomography (F18-FDG-PET). Results: Prevalence of OSA of any severity: 58,7% (Apnea Hypopnea Index (AHI)≥5/h), OSA in a moderate-to-severe extent (AHI≥15/h): 25%. Only 13.1% of MCI patients with OSA reported daytime sleepiness. MCI-OSA patients showed no specific neuropsychological pattern. Presence of OSA was not associated with specific AD biomarker profiles in the whole study group besides a positive association between AD positivity in an AD biomarker sub cohort. Conclusions: OSA is highly prevalent in patients with MCI. It might often remain undiagnosed as only a small number of MCI-OSA patients report daytime sleepiness. OSA could contribute to MCI symptoms and even to AD pathology. Further research is needed to validate these findings and to investigate possible pathophysiological relationships between OSA and MCI as well as between OSA and AD.