SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Aug. 9, 2024

The rising prevalence of diabetes mellitus has casted a spotlight on one its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for management, are increasingly studied their benefits. These benefits may include reduction oxidative stress and neuroinflammation, decrease amyloid burdens, enhancement neuronal plasticity, improved cerebral glucose utilization. multifaceted effects the relatively favorable side-effect profile SGLT2 inhibitors render them promising therapeutic candidate disorders. Nonetheless, application impairment is not without limitations, necessitating more comprehensive research to fully determine potential treatment. In this review, we discuss role in neural function, elucidate diabetes-cognition nexus, synthesize current knowledge based animal studies clinical evidence. Research gaps proposed spur further investigation.

Language: Английский

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Kidney-brain axis in the pathogenesis of cognitive impairment

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 200, P. 106626 - 106626

Published: Aug. 8, 2024

The kidney-brain axis is a bidirectional communication network connecting the kidneys and brain, potentially affected by inflammation, uremic toxin, vascular injury, neuronal degeneration, so on, leading to range of diseases. Numerous studies emphasize disruptions may contribute high morbidity neurological disorders, such as cognitive impairment (CI) in natural course chronic kidney disease (CKD). Although pathophysiology has not been fully elucidated, epidemiological data indicate that patients at all stages CKD have higher risk developing CI compared with general population. In contrast other reviews, we mentioned some commonly used medicines play pivotal role pathogenesis CI. Revealing interactions between damage brain function can reduce potential future This review will deeply explore characteristics, indicators, pathophysiological mechanisms CKD-related It provide theoretical basis for identifying progresses during ultimately prevents treats

Language: Английский

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Glucose Transport and Utilization in the Hippocampus: From Neurophysiology to Diabetes-Related Development of Dementia

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16480 - 16480

Published: Nov. 18, 2023

The association of diabetes with cognitive dysfunction has at least 60 years history, which started the observation that children type 1 mellitus (T1D), who had recurrent episodes hypoglycemia and consequently low glucose supply to brain, showed a deficit capacity. Later, growing incidence 2 (T2D) dementia in aged populations revealed their high association, reduced neuronal also been considered as key mechanism, despite hyperglycemia. Here, we discuss role functioning/preservation, how peripheral blood accesses intracellular compartment, including exquisite flux across blood–brain barrier (BBB) complex network transporters, dementia-related areas such hippocampus. In addition, insulin resistance-induced abnormalities hippocampus obese/T2D patients, inflammatory stress, oxidative mitochondrial increased generation advanced glycated end products BBB dysfunction, well dementia/Alzheimer’s disease, are addressed. Finally, these accompained by reduction expression translocation capacity insulin-sensitive transporter GLUT4 hippocampal neurons, leads neurocytoglycopenia eventually dysfunction. This knowledge should further encourage investigations into beneficial effects promising therapeutic approaches could improve central sensitivity expression, fight diabetes-related dysfunctions.

Language: Английский

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Insulin resistance as the molecular link between diabetes and Alzheimer's disease

World Journal of Diabetes, Journal Year: 2024, Volume and Issue: 15(7), P. 1430 - 1447

Published: July 8, 2024

Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies indicated possible link between DM an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays vital protecting brain functions. Insulin resistance (IR), especially prevalent type 2 diabetes, is believed to play significant AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various functions, making individuals more susceptible defining features, such as the buildup beta-amyloid plaques tau protein tangles. Emerging research suggests addressing insulin-related issues might help reduce or even reverse changes linked This review aims explore rela-tionship AD, with focus on IR. It explores molecular mechanisms by which IR lead assesses current treatments target Understanding IR's connection AD offers new possibilities highlights importance continued this interdisciplinary field.

Language: Английский

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Neuroprotective effects of dipeptidyl peptidase 4 inhibitor on Alzheimer’s disease: a narrative review

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 9, 2024

Insulin resistance in brain and amyloidogenesis are principal pathological features of diabetes-related cognitive decline development Alzheimer’s disease (AD). A growing body evidence suggests that maintaining glucose under control diabetic patients is beneficial for preventing AD development. Dipeptidyl peptidase 4 inhibitors (DDP4is) a class novel glucose-lowering medications through increasing insulin excretion decreasing glucagon levels have shown neuroprotective potential recent studies. This review consolidates extant from earlier new studies investigating the association between DPP4i use, AD, other outcomes. Beyond DPP4i’s benefits alleviating glucose-lowering, underlying mechanisms neuroprotection with were categorized into following sections: (Ferrari et al., Physiol Rev, 2021, 101, 1,047–1,081): DPP4is on directly ameliorating burden β-amyloid plaques reducing formation neurofibrillary tangles; bioactivity DPP4 substrates including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), stromal-derived factor-1α (SDF-1α) etc.; pleiotropic effects neuronal cells intracerebral structure anti-inflammation, anti-oxidation, anti-apoptosis. We further revisited recently published epidemiological provided supportive data to compliment preclinical evidence. Given there remains lack completed randomized trials aim at assessing effect progression, this expected provide useful insight inhibition as therapeutic target prevention treatment. The helpful informing rationales future clinical research guiding evidence-based practice.

Language: Английский

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Sodium–Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia

Annals of Internal Medicine, Journal Year: 2024, Volume and Issue: 177(10), P. 1319 - 1329

Published: Aug. 26, 2024

Both sodium–glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness preventing dementia remains uncertain.

Language: Английский

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Multimodal Precision Prevention - A New Direction in Alzheimer’s Disease

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

At least 40% of all dementia has been linked to modifiable risk factors suggesting a clear potential for preventative approaches targeting these factors. Despite the recent promising findings from anti-amyloid monoclonal antibodies, limited proportion patients are expected be eligible novel AD treatments. Given heterogeneous nature and complex multi-level pathological processes leading (involving, e.g., shared factors, interaction different pathology mechanisms, their putative synergistic effects on cognition), single may not sufficient halt or significantly impact disease progression. With exponentially increasing numbers world-wide, in parallel unprecedented population ageing, new multimodal therapy several mechanisms simultaneously urgently required. Developing next generation combination therapies with lifestyle intervention pharmacological treatments, implementing right interventions people at time, defining accessible sustainable strategies worldwide crucial. Here, we summarize state-of-the-art lifestyle-based approaches, especially lessons learned FINGER trial, prevention reduction cognitive impairment dementia. We also discuss some emerging underlying biological current development precision approaches. present an example trial design combining healthy changes repurposed disease-modifying drug place this study context World-Wide FINGERS, first interdisciplinary network trials dedicated

Language: Английский

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D’une longue pénurie thérapeutique au triomphe des nouvelles classes d’antidiabétiques dans des maladies non métaboliques

Médecine des Maladies Métaboliques, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

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Comparative risk of dementia in diabetic stroke patients prescribed SGLT2 vs. DPP-4 inhibitors: A propensity-matched retrospective cohort study

Journal of Stroke and Cerebrovascular Diseases, Journal Year: 2025, Volume and Issue: unknown, P. 108276 - 108276

Published: March 1, 2025

Diabetes is a significant risk factor for both stroke and dementia. This study aimed to compare the of incident dementia between sodium-glucose cotransporter 2 (SGLT2) inhibitors dipeptidyl peptidase-4 (DPP-4) in diabetic patients with history ischemic stroke. We conducted propensity-matched retrospective cohort using observational data from TriNetX global federated health research network. Patients aged 18 years or older type diabetes (T2D) stroke, newly prescribed either an SGLT2 DPP-4 inhibitor July 1, 2013, June 30, 2024, were included. Propensity score matching was employed balance baseline characteristics treatment groups. The primary outcome dementia, secondary outcomes including degenerative vascular After propensity matching, each group consisted 15901 patients. Over mean follow-up 2.52 years, use associated lower risks overall (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.59-0.74), (HR 0.68; CI 0.60-0.76), 0.59, 0.49-0.70) compared use. These findings remained consistent across various sensitivity subgroup analyses. In initiating inhibitors, association observed dementias. support preferential this high-risk population, warranting further investigation through randomized clinical trials.

Language: Английский

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Role of mitogen-activated protein kinase inhibitors in Alzheimer's disease: Rouge of brain kinases

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 224, P. 111296 - 111296

Published: March 10, 2025

Alzheimer's disease (AD) is the chief cause of dementia and related mortality worldwide due to progressive accumulation amyloid peptide (Aβ) hyperphosphorylated tau protein. These neuropathological changes lead cognitive impairment memory dysfunction. Notably, most Food drug Administration (FDA) approved anti-AD medications such as tacrine donepezil are engaged with symptomatic relief but do not reverse underlying AD neuropathology. Therefore, searching for new advisable. It has been shown that inflammatory signaling pathways mitogen-activated protein kinases (MAPK) intricate Aβ neuropathology in AD. In addition, inhibition brain MAPK plays a critical role mitigating dysfunction early-onset Though, fundamental mechanisms beneficial effects inhibitors were fully explained. this review aims discuss potential molecular

Language: Английский

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