Insights into Cognitive Brain Health in Chronic Kidney Disease

Review Article

Gerontol Geriatr Res. 2022; 8(2): 1074.

Insights into Cognitive Brain Health in Chronic Kidney Disease

Tariq H, Ramakrishnan M and Gupta A*

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, USA

*Corresponding author: Aditi Gupta, Associate Professor of Medicine, Division of Nephrology and Hypertension, Department of Internal Medicine, and Department of Neurology, 3901 Rainbow Blvd, Mail Stop 3002, Kansas City, KS 66160, USA

Received: June 30, 2022; Accepted: July 29, 2022; Published: August 05, 2022

Abstract

Cognitive impairment and Chronic Kidney Disease (CKD) are common in older adults. With advances in medicine, the average lifespan is expected to increase, further increasing the prevalence of both conditions. The mechanisms underlying cognitive impairment in CKD are unclear. While mild-moderately low estimated glomerular filtration rate (eGFR) may not be associated with cognitive impairment, severely decreased eGFR and albuminuria do. Patients on dialysis have a high prevalence of cognitive impairment. Cognitive function improves after kidney transplantation. However, some residual cognitive deficits persist after transplantation, indicating that restoring the kidney function alone may not be enough to restore cognitive function, and other etiological factors may play a role. Albuminuria, another marker of CKD is also associated with cognitive impairment. However, albuminuria is often undiagnosed. Improving early identification and management of patients with albuminuria may be a good population-based dementia prevention strategy. Other factors associated with cognitive impairment in CKD include anemia and other metabolic derangements commonly observed in CKD. In this article, we reviewed the prevalence of cognitive impairment in CKD, the potential mechanisms underlying cognitive impairment in CKD, and the current evidence on the association between cognitive impairment and eGFR and albuminuria.

Keywords: Albuminuria; Cognitive impairment; Chronic kidney disease; Dementia; eGFR; End stage kidney disease

Abbreviations

CKD: Chronic Kidney Disease; Egfr: Estimated Glomerular Filtration Rate; ESKD: End Stage Kidney Disease; CKD EPI: Chronic Kidney Disease Epidemiology Collaboration; MMSE: Mini Mental State Examination; 3MS: Modified Mini Mental State Examination; Moca: Montreal Cognitive Assessment; DSST: Digit Symbol Substitution Test; PTH: Parathyroid Hormone

Introduction

Cognitive impairment is common in patients with Chronic Kidney Disease (CKD) [1,2] and negatively impacts daily activities, quality of life, morbidity, mortality, and access to kidney transplantation [3-7]. Despite these adverse consequences, cognitive problems in patients with CKD are often unrecognized and untreated [6]. CKD itself remains under diagnosed limiting interventions to prevent dementia in this high-risk population. Even when diagnosed with CKD, patients remain unaware of their higher risk for cognitive impairment and dementia. The understanding of mechanisms underlying cognitive impairment in CKD is also limited, contributing to the lack of early preventive and management strategies. While there is growing interest in cognitive impairment in CKD, clear guidelines on diagnosis and management of CKD at risk for future dementia are lacking. In this review, we discuss the prevalence, pathophysiology, and future directions in cognitive impairment in CKD.

Epidemiology of Cognitive Impairment in CKD

CKD defined by an estimated glomerular filtration rate of <60mL/ min/1.73m², affects ~37 million adults in the United States [8] and has a prevalence of 38% in people 65 years or older. Similarly, dementia is also highly prevalent in the old, affecting ~6.2 million individuals, with a prevalence of 11% in people 65 years or older. With advances in medicine and increase in average life expectancy, the prevalence of both CKD and dementia is expected to increase further [9-11]. There is a wide variation in prevalence of cognitive impairment in CKD, partly due to different methodologies and thresholds used for defining cognitive impairment and dementia. A uniform approach to diagnosis and detect cognitive impairment in CKD is lacking. Cognitive function is affected in 27-62% of patients with CKD compared to 11-26% in age matched general population [12,14]. Furthermore, cognitive function worsens as the estimated glomerular filtration rate (eGFR) decreases [15-17] and patients with End Stage Kidney Disease (ESKD) have the highest prevalence of cognitive impairment of up to 87% [2,6,18-20]. Compared to the prevalence of dementia of 5% in the general population [21], patients with ESKD are 3-5 times more likely to have dementia with a prevalence of 10- 40% [6,22,23].

Just as cognitive impairment increases with age in the general population, cognitive impairment in CKD also increases with age. However, unlike the general population, cognitive impairment in CKD affects younger adults also [6,7]. The domains of cognition affected also seem to be different in CKD; common cognitive domains affected include executive function, attention, and memory [24,27]. These are different from other common etiologies of dementia such as Alzheimer’s disease that tends to affect memory more than some other domains. Furthermore, while cognitive impairment is often progressive and irreversible in the general population, cognitive function in CKD improves with kidney transplantation [28,29]. Despite this improvement, however, the prevalence of cognitive impairment in kidney transplant recipients is about 58%, much higher than the general population [30]. This indicates that factors other than impaired kidney function and low eGFR are at play. While the kidney function is restored after a kidney transplant, other factors such as vascular disease from longstanding hypertension or diabetes causing cognitive impairment may not be reversed with kidney transplantation. Conversely, it is possible that transplant associated factors such as surgery associated delirium or post-transplant immune suppression also affect post-transplant cognitive function.

Cognitive Impairment, eGFR and Albuminuria

Cognitive impairment in CKD increases with declining eGFR [15-17]. With over 20,000 participants, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study is the largest cross-sectional study evaluating the association between eGFR and cognitive function. Participants were 64.9 ± 9.6 years old, with a mean eGFR of 85.9 ± 23.7 mL/min/1.73m² (mean eGFR 47.7 ± 10.4 mL/ min/1.73m² for the 11% with CKD). Each 10 ml/min/1.73 m2 decrease in eGFR below 60 ml/min/1.73 m² was associated with an 11% increase in prevalence of cognitive impairment [31]. Table 1 summarizes some other cross-sectional studies showing similar associations. Some prospective studies also indicated a similar association between eGFR and cognitive impairment. The Cardiovascular Health Cognition Study included 3,349 participants without dementia and followed them for 6 years. A serum creatinine of >1.3mg/dl in women and >1.5mg/dl in men was associated with 37% increased risk of dementia [17]. The Rush Memory and Aging Project showed a higher rate of cognitive decline with a baseline eGFR of 15 mL/min/1.73 m² or lower; an effect similar to being additional 3 years older [32]. The INVADE study [33], the Northern Manhattan Study [34], and the Singapore Longitudinal Aging Study [35] also associated baseline kidney function with increased risk of cognitive decline.