Mechanisms of cognitive dysfunction in CKD

Viggiano, Davide; Wagner, Carsten A.; Martino, Gianvito; Zoccali, Carmine; Unwin, Robert J.; Capasso, Giovambattista

doi:10.1038/s41581-020-0266-9

Cited by 224 publications

(241 citation statements)

References 245 publications

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“…Mild cognitive impairment is a term used to identify people who are at risk of developing dementia, but the cognitive impairment is so mild that it does not affect daily activities. Symptoms of mild cognitive impairment include memory impairment, language difficulties, attention deficits, disorientation, and altered visuospatial skills [ 1 ]. The prevalence of mild cognitive impairment in individuals older than 65 years is approximately 3% to 22% [ 2 - 4 ].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness of Exergaming in Improving Cognitive and Physical Function in People With Mild Cognitive Impairment or Dementia: Systematic Review

Zhao

Feng

et al. 2020

JMIR Serious Games

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Background Individuals with mild cognitive impairment and dementia have impaired physical and cognitive functions, leading to a reduced quality of life compared with those without such impairment. Exergaming, which is defined as a combination of exercise and gaming, is an innovative, fun, and relatively safe way to exercise in a virtual reality or gaming environment. Therefore, exergaming may help people living with mild cognitive impairment or dementia to overcome obstacles that they may experience regarding regular exercise and activities. Objective The aim of this systematic review was to review studies on exergaming interventions administered to elderly individuals with mild cognitive impairment and dementia, and to summarize the results related to physical and cognitive functions such as balance, gait, executive function, and episodic memory. Methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, PsycINFO, Amed, and Nursing Database for articles published from the inception of the respective databases to January 2019. We included all clinical trials of exergaming interventions in individuals with mild cognitive impairment and dementia for review. The risk of bias was independently evaluated by two reviewers using the Cochrane Collaboration and Risk of Bias in Non-randomized Studies of Interventions tools. Results Ten studies involving 702 participants were included for review. There was consistent evidence from 7 studies with a low risk of bias showing statistically significant effects of exergaming on cognitive functioning in people with mild cognitive impairment and dementia. With respect to physical function, 3 of 5 full-scale studies found positive results, and the intensity of most games was classified as moderate. Conclusions Overall, exergaming is an innovative tool for improving physical and cognitive function in people with mild cognitive impairment or dementia, although there is high heterogeneity among studies in terms of the duration, frequency, and gaming platform used. The quality of the included articles was moderate to high. More high-quality studies with more accurate outcome indicators are needed for further exploration and validation of the benefits of exergaming for this population.

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Section: Introductionmentioning

confidence: 99%

Effectiveness of Exergaming in Improving Cognitive and Physical Function in People With Mild Cognitive Impairment or Dementia: Systematic Review

Zhao

Feng

et al. 2020

JMIR Serious Games

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“…Additionally, microvascular renal injury is a prominent feature of diabetes and hypertension, known as common causes of CKD and cognitive impairment [ 37 ]. Other mechanisms involve oxidative stress and inflammation, since increased serum levels of free radicals and pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor (TNF), and IL-1beta, contribute to both CKD progression [ 38 , 39 ] and neuroinflammation [ 40 ]. Additionally, serum levels of neuropeptide Y (NPY), parathormone (PTH), and fibroblast growing factor 23 (FGF 23) are commonly increased in CKD and seem to promote endothelial dysfunction in brain microcirculation [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Other mechanisms involve oxidative stress and inflammation, since increased serum levels of free radicals and pro-inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor (TNF), and IL-1beta, contribute to both CKD progression [ 38 , 39 ] and neuroinflammation [ 40 ]. Additionally, serum levels of neuropeptide Y (NPY), parathormone (PTH), and fibroblast growing factor 23 (FGF 23) are commonly increased in CKD and seem to promote endothelial dysfunction in brain microcirculation [ 38 ]. In contrast, decreased serum concentration of alpha-klotho, the co-receptor for FGF-23, has also been found in CKD [ 41 ] and is related to higher risk of dementia and cerebral white matter disease [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Comorbidities and complications of CKD, including anemia [ 43 ], depression [ 44 ], and gastrointestinal dysregulation with gut dysbiosis [ 45 ] may contribute to the development of cognitive impairment in CKD. Finally, CKD itself generates a toxic milieu with accumulation of several neurotoxins able to favor the onset of cognitive impairment [ 38 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

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Cognitive Impairment, Chronic Kidney Disease, and 1-Year Mortality in Older Patients Discharged from Acute Care Hospital

Rosa

D’Alia

Guarasci

et al. 2020

JCM

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The prognostic interaction between chronic kidney disease (CKD) and cognitive impairment is still to be elucidated. We investigated the potential interaction of overall cognitive impairment or defective constructional praxis and CKD in predicting 1-year mortality among 646 older patients discharged from hospital. The estimated glomerular filtration rate (eGFR) was calculated using the Berlin Initiative Study (BIS) equation. Cognitive impairment was assessed by the Mini Mental State Exam (MMSE) and defective constructional praxis was ascertained by the inherent MMSE item. The study outcome was 1-year mortality. Statistical analysis was carried out using Cox regression. After adjusting for potential confounders, the co-occurrence of eGFR <30 and overall cognitive impairment (Hazard Ratio (HR) = 3.12, 95% Confidence Interval (CI) = 1.26–7.77) and defective constructional praxis (HR = 2.50, 95% CI = 1.08–5.77) were associated with the outcome. No significant prognostic interaction of eGFR < 30 with either overall cognitive impairment (HR = 1.99, 95% CI = 0.38–10.3) or constructional apraxia (HR = 1.68, 95% CI = 0.33–8.50) was detectable, while only cognitive deficits were found significantly associated with the outcome in the interaction models (HR = 3.12, 95% CI = 1.45–6.71 for overall cognitive impairment and HR = 2.16, 95% CI = 1.05–4.45 for constructional apraxia). Overall cognitive impairment and defective constructional praxis may be associated with increased risk of 1-year mortality among older hospitalized patients with severe CKD. However, no significant prognostic interaction between CKD and cognitive impairment could be observed.

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“…As the uremic phenotype is associated by behavioral impairments, such as dementia, depression and cognitive deficits (95) and Klotho enhances oligodendrocyte maturation and myelination of the CNS (96), the low Klotho state of CKD may contribute to the common manifestations of central nervous system dysfunction in CKD. The specific role of the low Klotho state in the complicated scenario of uremic cognitive dysfunction (97) and disruption of the blood-brain barrier when renal function declines (98) deserves further studies.…”

Section: Klotho In Ckdmentioning

confidence: 99%

Klotho, Aging, and the Failing Kidney

et al. 2020

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Klotho has been recognized as a gene involved in the aging process in mammals for over 30 years, where it regulates phosphate homeostasis and the activity of members of the fibroblast growth factor (FGF) family. The α-Klotho protein is the receptor for Fibroblast Growth Factor-23 (FGF23), regulating phosphate homeostasis and vitamin D metabolism. Phosphate toxicity is a hallmark of mammalian aging and correlates with diminution of Klotho levels with increasing age. As such, modulation of Klotho activity is an attractive target for therapeutic intervention in the diseasome of aging; in particular for chronic kidney disease (CKD), where Klotho has been implicated directly in the pathophysiology. A range of senotherapeutic strategies have been developed to directly or indirectly influence Klotho expression, with varying degrees of success. These include administration of exogenous Klotho, synthetic and natural Klotho agonists and indirect approaches, via modulation of the foodome and the gut microbiota. All these approaches have significant potential to mitigate loss of physiological function and resilience accompanying old age and to improve outcomes within the diseasome of aging.

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Mechanisms of cognitive dysfunction in CKD

Cited by 224 publications

References 245 publications

Effectiveness of Exergaming in Improving Cognitive and Physical Function in People With Mild Cognitive Impairment or Dementia: Systematic Review

Effectiveness of Exergaming in Improving Cognitive and Physical Function in People With Mild Cognitive Impairment or Dementia: Systematic Review

Cognitive Impairment, Chronic Kidney Disease, and 1-Year Mortality in Older Patients Discharged from Acute Care Hospital

Klotho, Aging, and the Failing Kidney

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