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    Albuminuria as a risk factor for mild cognitive impairment and dementia—what is the evidence?
    (Nephrol Dial Transplant, 2021) Bikbov, Boris; Soler, Maria Jose; Pesic, Vesna; Capasso, Giovambattista; Unwin, Robert; Endres, Matthias; Remuzzi, Giuseppe; Perico, Norberto; Gansevoort, Ron; Mattace-Raso, Francesco; Bruchfeld, Annette; Figurek, Andreja; (Cognitive Decline in Nephro-Neurology European Cooperative Target; Hafez, Gaye
    Kidney dysfunction can profoundly influence many organ systems, and recent evidence suggests a potential role for increased albuminuria in the development of mild cognitive impairment (MCI) or dementia. Epidemiological studies conducted in different populations have demonstrated that the presence of increased albuminuria is associated with a higher relative risk of MCI or dementia both in cross-sectional analyses and in studies with long-term follow-up. The underlying pathophysiological mechanisms of albuminuria’s effect are as yet insufficiently studied, with several important knowledge gaps still present in a complex relationship with other MCI and dementia risk factors. Both the kidney and the brain have microvascular similarities that make them sensitive to endothelial dysfunction involving different mechanisms, including oxidative stress and inflammation. The exact substrate of MCI and dementia is still under investigation, however available experimental data indicate that elevated albuminuria and low glomerular filtration rate are associated with significant neuroanatomical declines in hippocampal function and grey matter volume. Thus, albuminuria may be critical in the development of cognitive impairment and its progression to dementia. In this review, we summarize the available evidence on albuminuria’s link to MCI and dementia, point to existing gaps in our knowledge and suggest actions to overcome them. The major question of whether interventions that target increased albuminuria could prevent cognitive decline remains unanswered. Our recommendations for future research are aimed at helping to plan clinical trials and to solve the complex conundrum outlined in this review, with the ultimate goal of improving the lives of patients with chronic kidney disease.
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    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.
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    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, Sophie
    There 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.