Potential role of ghrelin in neuroprotection and cognitive function: implications for diabetic cognitive impairment

PeerJ, Journal Year: 2025, Volume and Issue: 13, P. e18898 - e18898

Published: Feb. 21, 2025

Ghrelin is a class of brain and intestinal peptides. It regulates food intake body glucose levels maintains cellular homeostasis. In recent years, research has revealed that ghrelin may positively impact learning memory. Despite ghrelin’s multiple functions in the central nervous system, its use as therapeutic agent for neurologic dysfunction remains unclear. Diabetic cognitive impairment (DCI) severe neurological complication diabetes mellitus. Its incidence increasing comorbidity endocrinology neurology. Additionally, it risk factor Alzheimer’ s disease (AD). are altered patients with mellitus combined impairment. Furthermore, modulation improved function rats DCI. These findings suggest potential importance pathogenesis This article presents comprehensive review DCI by mimics. this study elucidates prospects mimics DCI, aiming to identify novel targets avenues prevention management future.

Language: Английский

---

Cognitive disorders in diabetes

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2025, Volume and Issue: 6

Published: Feb. 24, 2025

Diabetes is increasingly recognized as a condition with far-reaching implications, including its impact on cognitive health (1). Early observations of the relationship between diabetes and impairment date back over century, initially based simple neuropsychological assessments comparing individuals without diabetes. Since then, large-scale epidemiological studies, advanced imaging technologies, neuropathological investigations have solidified this association, revealing complex interplay metabolic dysregulation decline (2,3). mis en forme : Anglais (Royaume-Uni) Code de champ modifié (Royaume-Uni)Today, it well-established that type 2 face 1.6-fold greater risk developing dementia compared to their non-diabetic peers. Estimates suggest affects 20% 70% people diabetes, depending study population examined (4). Beyond daily living, in associated higher cardiovascular events mortality Today, (5). The disorders shaped by multiple interacting factors, among which socioeconomic status plays crucial role. Education level, key determinant status, has been widely studied shown influence Individuals education tend lower risk, while those are more susceptible lifestyle-related diseases such hypertension, obesity, these conditions also decline, from backgrounds may experience severe rapid deterioration functions when living (6). This interconnected suggests disparities not only increase but contribute an accelerated through prevalence other diseases.Of note, recent COVID-19 pandemic demonstrated infected patients develop levels anxiety depression, well increased decline. Given at infections, can be hypothesized infection directly or indirectly worsen amplify diabetic (7). However, precise remains fully established.. For elderly individuals, particularly coexisting dementia, managing effectively becomes challenging. growing global projections pointing even steeper rise coming decades, diabetes-related emerging critical public challenge. These diminish quality life for millions worldwide impose substantial economic burdens healthcare systems both direct costs, treatments, indirect like lost productivity caregiving expenses.Cognitive now acknowledged significant complication It encompasses spectrum disorders, mild profoundly affect individuals' memory, attention, decision-making abilities. impairments complicate everyday activities, self-management creating feedback loop worsening glycemic control (8). Patients dysfunction often behavioral psychological challenges further impede ability follow medical advice, adhere treatment regimens, maintain consistent blood glucose monitoring. difficulties lead reduced adherence, less frequent monitoring, variability. cascading effects include recurrent episodes hypo-and hyperglycemia, exacerbate selfmanagement (9). vicious cycle compounded inherently demanding nature management. Decision-making about insulin dosing, meal planning, physical activity, medication adherence complex, requiring effort throughout day. impaired function, demands prove overwhelming, increasing complications diminishing (10).Research uncovered several factors contributing dual burden impairment. poor control, hypoglycemia, age, detrimental social isolation. Each exacerbates faced complicates Despite issues, awareness understanding professionals remain inadequate. Many report feeling unsupported misunderstood attempting address challenges, emphasizing urgent need enhanced specialized training providers (3).Adding complexity, develops insidiously, early subtle signs manifesting during middle age or, some cases, before 40 symptoms frequently overlooked attributed causes, delaying diagnosis intervention. highlights importance implementing proactive screening detection strategies, could significantly mitigate progression improve patient outcomes. despite recognition issue, integration into management guidelines relatively advancement. While represents positive step forward, application routine clinical practice inconsistent fragmented. To bridge gap, efforts needed standardize approaches, incorporate care, ensure teams equipped tools knowledge necessary effectively. will require improved commitment reshaping care models better serve burden.Despite awareness, gaps Current practices lack clear consensus most effective, how should performed, what thresholds prompt American Association (ADA) recommends annual aged 65 older, no specific guidance exists younger adults, evidence occur (11).While (11).Emerging therapies offer potential hope. Recently, FDA approved two anti-amyloid monoclonal antibodies Alzheimer's disease. treatments represent breakthroughare considered promising development, role populations unclear. Similarly, GLP-1 receptor agonists (GLP-1RAs), used management, neuroprotective preclinical studies neurodegenerative (12,13). preventing mitigating yet determined. In addition, use sodium-glucose cotransporters-2 inhibitors, another class novel anti-diabetic therapeutic agents, deficits, although exact mechanisms involved still elucicated (14). . Most existing expert opinion rather than robust data, underscoring comprehensive research. Longitudinal larger cohorts extended follow-up periods essential establish evidence-based practices. Technological advances, continuous monitoring (CGM), solutions improving CGMs enable real-time tracking levels, providing insights variability (15,16). accuracy limited extreme research optimize impairments.To impairment, collaborative, multidisciplinary approach just beneficial, -it essential. involve diverse team professionals, endocrinologists, specialists, primary physicians, educators, dietitians, therapists. By pooling expertise, create model optimizes resources, customizes meet unique needs each individual, ensures seamless pharmacological non-pharmacological strategies.In addition provided teams, professional societies hold pivotal catalyzing systemic change. organizations spearhead broad-based educational initiatives aimed providers, focusing raising intersection disorders. Such development targeted, patient-centered materials simplify information, making accessible actionable families affected conditions. Moreover, fostering stronger collaboration various specialties disciplines addressing multifaceted posed burden. Increased investment initiatives, terms funding strategic enhance manage overlapping impacts Through concerted efforts, system move toward holistic approach, ultimately outcomes affected.The link crisis. creates self-perpetuating undermines patients' Addressing issue requires deepen our underlying mechanisms, tailored strategies. New technologies already playing support older adults They efficient response fluctuations patient's needs, provide caregivers remote capabilities faster intervention crises, assist adjusting updating long-term plans patterns observed data collected. Furthermore, help evaluate selfmanagementAs continues obesity rates rise, diabetesrelated set dramatically. calls immediate action researchers, policymakers alike. investing advancing research, promoting we challenge worldwide.

Language: Английский

---

The impact of lactate on diabetic cognitive dysfunction: Insights from energy metabolism to epigenetic modulation

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(4), P. 167749 - 167749

Published: Feb. 26, 2025

This manuscript elucidates the intricate roles of lactate in Diabetic Cognitive Dysfunction (DCD), extending beyond its conventional role as an energy substrate. The investigation centers on participation metabolism and epigenetic modulation, with a particular emphasis influence cognitive faculties through histone lactylation. discourse scrutinizes lactate's part metabolic equilibrium central nervous system, encompassing fluctuating concentrations under various conditions pivotal function within Astrocyte-Neuron Lactate Shuttle (ANLS) mechanism conduit. involvement DCD is multilayered, pathways, cellular signaling cascades, regulation gene expression. Dysregulation lactylation process may modulate neuronal functionality by impacting genes integral to neuroplasticity capabilities. These revelations offer novel insights into molecular underpinnings lay groundwork for discovery potential therapeutic targets. Subsequent scholarly endeavors are poised dissect nuanced mechanisms which exert DCD, pinpointing critical modulated assessing their ramifications signal transduction pathways. Given regulatory dynamics lactate, contingent upon concentration, temporal factors, disease etiology, more profound elucidation necessitates augmented cadre animal experimentation clinical observational research. Such investigative pursuits anticipated yield innovative approaches methodologies comprehensive management spanning prevention, diagnosis, intervention.

Language: Английский

---

Apelin‐13 Alleviates Diabetes‐Associated Cognitive Decline by Reducing Oxidative Stress and Mitochondrial Dysfunction via the SIRT3/Foxo3 Pathway

Biotechnology and Applied Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

ABSTRACT The incidence of diabetes‐related cognitive dysfunction is on the rise, yet clinical interventions to prevent this condition remain limited. Apelin‐13, an endogenous peptide known for its positive inotropic and vasoactive properties, has been shown exert diverse effects across various tissues cell types. However, potential protective role in diabetes‐associated decline (DACD) remains poorly understood. To investigate this, we established a rodent diabetes model using high‐fat diet (HFD) combined with streptozotocin (STZ, intraperitoneal injection, 60 mg/kg). Cognitive function was evaluated Morris water maze Y‐maze tests. Additionally, employed range techniques, including glucose tolerance tests (IPGTT), insulin (ITT), immunofluorescence labeling, real‐time PCR, Western blot analysis, enzyme‐linked immunosorbent assays (ELISA). Our results demonstrate that apelin‐13 administration alleviated symptoms diabetic mouse model. Specifically, improved performance both In hippocampus treated mice, reduced oxidative stress by enhancing activity superoxide dismutase (SOD) catalase (CAT), while decreasing levels malondialdehyde (MDA) 4‐hydroxynonenal (4‐HNE). Furthermore, mitochondrial restoring activities COX I IV (but not II) increasing ATP production. Apelin‐13 also restored SIRT3 expression elevated NAD+/NADH ratio hippocampus. As result, facilitated deacetylation nuclear translocation Foxo3a When silenced, beneficial stress, function, impairment mice were significantly diminished, underscoring critical these processes. summary, our findings suggest mitigates DACD reducing through SIRT3/Foxo3 pathway. These highlight as promising therapeutic candidate DACD.

Language: Английский

---

Evaluating the relationship between inflammatory markers and preoperative delirium in elderly hip fracture patients: A retrospective observational study

Medicine, Journal Year: 2025, Volume and Issue: 104(10), P. e41569 - e41569

Published: March 7, 2025

Preoperative delirium is common and associated with poor clinical outcomes in elderly hip fracture patients. Although inflammatory markers have shown potential predicting postoperative delirium, their relevance to preoperative remains unclear. This study aimed investigate the relationship between improve risk prediction management strategies. We retrospectively studied 548 patients aged 70 years or older. The primary outcome was diagnosed using Confusion Assessment Method (CAM). Explanatory variables included (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte [PLR], systemic immune-inflammation index [SII], burden [IBI], inflammation response [SIRI]). About 7.66% of developed study. These were more likely be older, comorbid cardiovascular disease, transferred an internal medicine ward for further treatment (P < .001). Multivariate analysis revealed that older age (OR = 1.11, 95% CI 1.04-1.18) disease 2.94, 1.51-5.67) independently occurrence delirium. No significant differences observed groups markers: NLR .70), PLR .09), IBI SII .21), SIRI .80). Older comorbidities independent factors associations found markers. Future research should explore additional biomarkers refine stratification this population.

Language: Английский

---

The effects of risperidone and voluntary exercise intervention on synaptic plasticity gene expressions in the hippocampus and prefrontal cortex of juvenile female rats

Physiology & Behavior, Journal Year: 2025, Volume and Issue: unknown, P. 114879 - 114879

Published: March 1, 2025

Psychiatric disorders and antipsychotics are associated with impaired neuroplasticity, while physical exercise has been reported to enhance neuroplasticity improve cognitive affective processes. Therefore, this study hypothesizes that voluntary can synaptic plasticity in juvenile rats disrupted by risperidone, a commonly prescribed antipsychotic for pediatric patients. Thirty-two female were randomly assigned Vehicle+Sedentary, Risperidone (0.9mg/kg; b.i.d)+Sedentary, Vehicle+Exercise (three hours daily access running wheels), Risperidone+Exercise groups four week treatment. Brains collected further analysis. In the hippocampus, mRNA expressions of Bdnf, Ntrk2, Grin2b increased risperidone intervention. Exercise upregulated expression Grin1 Grin2a. Syn1 Syp enhanced risperidone-treated group. The both Mfn1 Drp1 decreased risperidone-only prefrontal cortex, Bdnf Dlg4 was exercise, Ntrk2 reduced reversed exercise. or without risperidone-decreased Ppargc1α gene affects through complex mechanism rats: enhancing certain key genes hippocampus inhibiting essential mitochondrial function. line our hypothesis, promotes beneficial enhances specific rats.

Language: Английский

---

A red lentils-based synbiotic cookie exerts neuroprotective effects in a mouse model of Alzheimer's disease

The Journal of Nutritional Biochemistry, Journal Year: 2025, Volume and Issue: unknown, P. 109904 - 109904

Published: March 1, 2025

Language: Английский

---

Risk Factors and Predictors of Cognitive Impairment in Older Adults: A Retrospective Cross-Sectional Study

Archives of Gerontology and Geriatrics Plus, Journal Year: 2025, Volume and Issue: unknown, P. 100154 - 100154

Published: April 1, 2025

Language: Английский

---

Balanced Steady-State Free Precession Enables High-Resolution Dynamic 3D Deuterium Metabolic Imaging of the Human Brain at 7T

Investigative Radiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Objectives Deuterium ( 2 H) metabolic imaging (DMI) is an emerging magnetic resonance technique to non-invasively map human brain glucose (Glc) uptake and downstream metabolism following oral or intravenous administration of H-labeled Glc. The achievable spatial resolution limited due inherently low sensitivity DMI. This hinders potential clinical translation. purpose this study was improve the signal-to-noise ratio (SNR) 3D DMI via a balanced steady-state free precession (bSSFP) acquisition scheme combined with fast non-Cartesian spatial-spectral sampling enable high-resolution dynamic neural Glc glutamate+glutamine (Glx) synthesis at 7T. Materials Methods Six healthy volunteers (2 f/4 m) were scanned after 0.8 g/kg [6,6′]- H-Glc using novel density-weighted bSSFP concentric ring trajectory (CRT) k-space Time-resolved whole datasets acquired for approximately 80 minutes (7 per dataset) 0.75 mL 0.36 isotropic results compared conventional spoiled Free Induction Decay (FID) H-MRSI CRT readout matched nominal resolution. Dynamic measurements accompanied by simultaneous systemic interstitial fluid continuous monitoring (CGM) sensor (on upper arm). correlation between levels analyzed linear mixed models. Results bSSFP-CRT approach achieved SNRs that up 3-fold higher than FID-CRT H-MRSI. enabled 2-fold Seventy tracer comparable H-Glc, H-Glx, H-water concentrations detected both schemes both, regular high resolutions (0.75 ml isotropic). mean Areas Under Curve (AUC) obtained CGM 509 ± 65 mM·min. 3.4 times AUC 149 43 mM·min models fitted assess relationship measures yielded statistically significant slope estimates in GM (β 1 = 0.47, P 0.01) WM 0.36, 0.03). Conclusions In we successfully implemented whole-brain A SNR increase allowed us double Systemic measurements, DMI, demonstrate applications. could help our understanding linking it time-resolved peripheral levels. Importantly, these are conducted minimally invasive physiological manner.

Language: Английский

---

The impact of prolonged high-concentration cortisol exposure on cognitive function and risk factors: Evidence from Cushing's disease patients

Journal of Alzheimer s Disease Reports, Journal Year: 2025, Volume and Issue: 9

Published: Jan. 1, 2025

Background Prolonged high-concentration cortisol exposure may impair cognitive function, but its mechanisms and risk factors remain unclear in humans. Objective Using Cushing's disease patients as a model, this study explores these effects develops predictive model to aid managing high-risk patients. Methods This single-center retrospective included 107 (January 2020–January 2024) at the First Medical Center of PLA General Hospital. Cognitive assessed using Montreal Assessment, revealed 58 with impairment 49 normal function. Patients were divided into training (n = 53) validation cohorts 54) for constructing validating model. Risk identified via univariate analysis least absolute shrinkage selection operator regression, nomogram prediction was developed. Performance evaluated receiver operating characteristic (ROC) curves, calibration decision curve (DCA). Results Cortisol AM/PM ratio, 8 a.m. concentration, body mass index, fasting plasma glucose significant impairment. The demonstrated strong ability, ROC values 0.80 (training) 0.91 (validation). DCA indicated superior clinical utility compared treating all or no Conclusions confirms impact prolonged high on function identifies key factors. offers robust performance, providing valuable tool patients’ health informing strategies other cortisol-related disorders.

Language: Английский

---