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Öğe Cholinergic system in patients with chronic kidney disease: cognitive and renal implications(2025) Xu, Hong; Eriksdotter, Maria; Hafez, Gaye; Sumonto, Mitra; Bruchfeld, Annette; Pesic, Vesna; Unwin, Robert; Wagner, Carden A.; Massy, Carsten; Massy, Ziad A.; Zoccali, Carmine; Pepin, Marion; Capasso, Giovambattista; Liabeuf, Sophie; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target)Cholinergic synapses are widespread throughout the human central nervous system. Their high density in the thalamus, neocortex, limbic system, and striatum suggests that cholinergic transmission plays a vital role in memory, attention, learning and other higher cognitive functions. As a result, the brain's cholinergic system occupies a central position in research on normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. In addition to its role in the brain, neuronal cholinergic pathways are essential for the physiological regulation of bodily organs, including the kidneys, through the parasympathetic branch of the peripheral nervous system. Chronic kidney disease (CKD) is a non-communicable disease with a global prevalence of approximately 10%. Cognitive impairment is common among patients with CKD, with reported prevalence rates ranging from 30% to 60%, depending on definitions and assessment methods used. Given the importance of the cholinergic system in cognitive processes, it may be a key area of focus for evaluating cognitive function in this population. In this current narrative review, we will first examine evidence linking the cholinergic system to cognitive functions; with a specific focus on drugs that affect this system. we will then discuss the potential implications of cholinergic function in patients with CKD.Öğe Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor(2023) Liabeuf, Sophie; Pesic, Vesna; Spasovski, Goce; Maciulaitis, Romaldas; Bobot, Mickael; Farinha, Ana; Wagner, Carsten A.; Unwin, Robert J.; Capasso, Giovambattista; Bumblyte, Inga Arune; Hafez, GayePeople living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood-brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.Öğe Drugs with a negative impact on cognitive functions (Part 2): drug classes to consider while prescribing in CKD patients(2023) Hafez, Gaye; Malyszko, Jolanta; Golenia, Aleksandra; Klimkowicz-Mrowiec, Aleksandra; Ferreira, Ana Carina; Arıcı, Mustafa; Bruchfeld, Annette; Nitsch, Dorothea; Massy, Ziad A.; Pepin, Marion; Capasso, Giovambattista; Mani, Laila-Yasmin; Liabeuf, SophieThere is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood-brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects.Öğe Drugs with a negative impact on cognitive functions (part 3): antibacterial agents in patients with chronic kidney disease(2024) Liabeuf, Sophie; Hafez, Gaye; Pesic, Vesna; Spasovski, Goce; Bobot, Mickael; Maciulaitis, Romaldas; Bumblyte, Inga Arune; Ferreira, Ana Carina; Farinha, Ana; Malyszko, Jolanta; Pepin, Marion; Massy, Ziad A.; Unwin, Robert; Capasso, Giovambattista; Mani, Laila-Yasmin; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target)The relationship between chronic kidney disease (CKD) and cognitive function has received increased attention in recent years. Antibacterial agents (ABs) represent a critical component of therapy regimens in patients with CKD due to increased susceptibility to infections. Following our reviewing work on the neurocognitive impact of long-term medications in patients with CKD, we propose to focus on AB-induced direct and indirect consequences on cognitive function. Patients with CKD are predisposed to adverse drug reactions (ADRs) due to altered drug pharmacokinetics, glomerular filtration decline, and the potential disruption of the blood-brain barrier. ABs have been identified as a major cause of ADRs in vulnerable patient populations. This review examines the direct neurotoxic effects of AB classes (e.g. beta-lactams, fluoroquinolones, aminoglycosides, and metronidazole) on the central nervous system (CNS) in patients with CKD. We will mainly focus on the acute effects on the CNS associated with AB since they are the most extensively studied effects in CKD patients. Moreover, the review describes the modulation of the gut microbiota by ABs, potentially influencing CNS symptoms. The intricate brain-gut-kidney axis emerges as a pivotal focus, revealing the interplay between microbiota alterations induced by ABs and CNS manifestations in patients with CKD. The prevalence of antibiotic-associated encephalopathy in patients with CKD undergoing intravenous AB therapy supports the use of therapeutic drug monitoring for ABs to reduce the number and seriousness of ADRs in this patient population. In conclusion, elucidating AB-induced cognitive effects in patients with CKD demands a comprehensive understanding and tailored therapeutic strategies that account for altered pharmacokinetics and the brain-gut-kidney axis.Öğe Efficacy of erythropoietin as a neuroprotective agent in CKD-associated cognitive dysfunction: A literature systematic review(2024) Barbieri, Michelangela; Chiodini, Paolo; Di Gennaro, Piergiacomo; Hafez, Gaye; Liabeuf, Sophie; Malyszko, Jolanta; Mani, Laila-Yasmin; Raso, Francesco Mattace; Pepin, Marion; Perico, Norberto; Simeoni, Mariadelina; Zoccali, Carmine; Tortorella, Giovanni; Capuano, Annalisa; Remuzzi, Giuseppe; Capasso, Giovambattista; Paolisso, Giuseppe; CONNECT Action (Cognitive Decline in Nephro-Neurology European Cooperative Target) collaboratorsPatients with chronic kidney disease (CKD) often experience mild cognitive impairment and other neurocognitive disorders. Studies have shown that erythropoietin (EPO) and its receptor have neuroprotective effects in cell and animal models of nervous system disorders. Recombinant human EPO (rHuEPO), commonly used to treat anemia in CKD patients, could be a neuroprotective agent. In this systematic review, we aimed to assess the published studies investigating the cognitive benefits of rHuEPO treatment in individuals with reduced kidney function. We comprehensively searched Pubmed, Cochrane Library, Scopus, and Web of Science databases from 1990 to 2023. After selection, 24 studies were analyzed, considering study design, sample size, participant characteristics, intervention, and main findings. The collective results of these studies in CKD patients indicated that rHuEPO enhances brain function, improves performance on neuropsychological tests, and positively affects electroencephalography measurements. These findings suggest that rHuEPO could be a promising neuroprotective agent for managing CKD-related cognitive impairment.Öğe Methodological challenges and biases in the field of cognitive function among patients with chronic kidney disease(Frontiers Media SA, 2023) Giannakou, Konstantinos; Golenia, Aleksandra; Liabeuf, Sophie; Malyszko, Jolanta; Mattace-Raso, Francesco; Farinha, Ana; Spasovski, Goce; Hafez, Gaye; Wiecek, Andrzej; Capolongo, Giovanna; Capasso, Giovambattista; Massy, Ziad A.Chronic kidney disease (CKD) affects approximately 850 million people globally and is associated with an increased risk of cognitive impairment. The prevalence of cognitive impairment among CKD patients ranges from 30 to 60%, and the link between CKD and cognitive impairment is partially understood. Methodological challenges and biases in studying cognitive function in CKD patients need to be addressed to improve diagnosis, treatment, and management of cognitive impairment in this population. Here, we review the methodological challenges and study design issues, including observational studies’ limitations, internal validity, and different types of bias that can impact the validity of research findings. Understanding the unique challenges and biases associated with studying cognitive function in CKD patients can help to identify potential sources of error and improve the quality of future research, leading to more accurate diagnoses and better treatment plans for CKD patients.
