Cognitive Impairment and Dementia in Older Adults With Chronic Kidney Disease

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Abstract

Individuals with chronic kidney disease (CKD), especially older adults, are at more risk of experiencing cognitive impairment, possibly leading to mild cognitive impairment and/or dementia. Studies report associations between CKD and cognitive impairment; although unclear, there seems to be a graded association between stage of CKD and affected cognitive domains, with executive function being affected earlier in the process than episodic memory and global ability. In CKD, dysexecutive mild cognitive impairment and vascular dementia are also more prominent than other subtypes. Explanations are directed toward traditional and nontraditional vascular factors, which may also explain or mediate the association between CKD and type of cognitive impairment. Future research is urged to focus on the longitudinal association between specific domains of cognitive function, including executive function and memory and CKD; to develop screening tools fit for every CKD stage in elderly individuals, and lastly, to use imaging methods that may help clarify the underlying mechanisms connecting the kidney and the brain.

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Most cited references 38

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Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency.

Anthony J Bleyer, Casey Crump, Linda F. Fried … (2003)

Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease. The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar. Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.

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Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study.

Catherine Stehman-Breen, A L Fitzpatrick, Stephen Seliger … (2004)

Renal impairment is associated with an increased risk of carotid atherosclerosis and stroke, determinants of cognitive dysfunction and dementia. The purpose of this study was to determine whether moderate renal impairment is associated with incident dementia among community-dwelling older adults. Participants in the Cardiovascular Health Cognition Study without prevalent dementia (n = 3349) were included in the analysis. Incident dementia was confirmed through neurologic testing. Renal function at baseline was estimated by the inverse of serum creatinine (1/SCr); moderate renal impairment was defined as SCr > or = 1.3 mg/dl for women and > or = 1.5 mg/dl for men. Cox regression models were used to estimate the association of renal impairment with incident dementia. Because SCr is also a function of muscle mass, the authors determined whether the relationship between SCr and dementia was particularly strong among individuals without severe co-morbidity at baseline, as reflected by self-reported general health status. There were 477 incident dementia cases over a median 6 yr follow-up. After adjustment for potential confounders, moderate renal insufficiency was associated with a 37% increased risk of dementia (95% CI = 1.06 to 1.78). Similarly, a 0.5-unit decrement in 1/SCr (equivalent to an increase in SCr from 1.0 to 2.0 mg/dl) was associated with a 26% increased risk (95% CI = 1.02 to 1.60). These associations were present only among the 84% of older adults who reported good-excellent health. Among those in good-excellent health, higher SCr was associated with vascular-type dementia but not Alzheimer-type dementia. Moderate renal impairment, reflected by a higher SCr, is associated with an excess risk of incident dementia among individuals in good-excellent health. Strategies to prevent or delay the onset of dementia in patients with moderate renal impairment are needed.

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Impact of anemia on mortality, cognition, and function in community-dwelling elderly.

M Kuchibhatla, D Marty Denny, Gary Cohen (2006)

To explore the impact of varying hemoglobin levels on mortality, function, and cognition in a representative population of older persons. Participants in this prospective cohort study included 1 744 men and women, aged 71 years or older, from a random household sample living in Durham and surrounding counties in North Carolina. Hemoglobin levels were obtained from participants at baseline in 1992. Functional status was measured at the 4-year follow-up interview using Katz and instrumental activities of daily living. Cognition was measured using the Short Portable Mental Status Questionnaire (SPMSQ). Death was determined by search of the National Death Index, and all deaths through 2000 are included. Using World Health Organization (WHO) criteria, the prevalence of anemia was 24%. There was a strong racial difference with an odds ratio, adjusted for age, education, estimated glomerular filtration rate and comorbidity of 3.0 (95% CI, 2.3-3.9) in African Americans compared with Caucasians. The risk ratio for 8-year mortality was 1.7 (95% CI, 1.5-2.0) for anemic subjects (P = .0001) and did not differ by sex or race. Anemia was strongly associated with poorer physical function (P = .0001) and cognitive function (P = .0001), and predicted decreases in both over a 4-year period. In an elderly community-based population, anemia is more prevalent in African Americans and is independently associated with increased mortality over 8 years for both races and sexes. Anemia also is a risk factor for functional and cognitive decrease.