Cystatin C as a marker of cognitive function in elders: Findings from the health ABC study

Yaffe, Kristine; Lindquist, Karla; Shlipak, Michael G.; Simonsick, Eleanor M.; Fried, Linda F.; Rosano, Caterina; Satterfield, Suzanne; Atkinson, Hal H.; Windham, B. Gwen; Tamura, Manjula Kurella

doi:10.1002/ana.21383

Cited by 109 publications

(129 citation statements)

References 18 publications

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“…For example, previous studies have shown cognitive decline associated with markers of inflammation 25,26 and chronic kidney disease. 27,28 Vascular disease also is known to contribute to cognitive impairment. 29,30 We did not have MRI brain scans that might have detected subclinical cerebral infarcts.…”

Section: Resultsmentioning

confidence: 99%

Advanced glycation end product level, diabetes, and accelerated cognitive aging

Yaffe¹,

Lindquist²,

Schwartz³

et al. 2011

Neurology

129

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Objective: Several studies report that diabetes increases risk of cognitive impairment; some have hypothesized that advanced glycation end products (AGEs) underlie this association. AGEs are cross-linked products that result from reactions between glucose and proteins. Little is known about the association between peripheral AGE concentration and cognitive aging. Methods:We prospectively studied 920 elders without dementia, 495 with diabetes and 425 with normal glucose (mean age 74.0 years). Using mixed models, we examined baseline AGE concentration, measured with urine pentosidine and analyzed as tertile, and performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident cognitive impairment (a decline of Ͼ1.0 SD on each test) was analyzed with logistic regression.Results: Older adults with high pentosidine level had worse baseline DSST score (p ϭ 0.05) but not different 3MS score (p ϭ 0.32). On both tests, there was a more pronounced 9-year decline in those with high and mid pentosidine level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point decline, p overall Ͻ0.001; DSST 5.9, 7.4, and 4.5 point decline, p ϭ 0.03). Incident cognitive impairment was higher in those with high or mid pentosidine level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio ϭ 1.55; 95% confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio ϭ 1.62; 95% confidence interval 1.13-2.33). There was no interaction between pentosidine level, diabetes status, and cognitive decline. Multivariate adjustment for age, sex, race, education, hypertension, cardiovascular disease, estimated glomerular filtration rate, and diabetes diminished results somewhat but overall patterns remained similar. Conclusion:High peripheral AGE level is associated with greater cognitive decline in older adults with and without diabetes. Neurology ® 2011;77:1351-1356 GLOSSARY 3MS ϭ Modified Mini-Mental State Examination; A␤ ϭ ␤-amyloid; AD ϭ Alzheimer disease; ADA ϭ American Diabetes Association; AGE ϭ advanced glycation end product; BMI ϭ body mass index; CES-D ϭ Center for Epidemiologic Studies-Depression Scale; CI ϭ confidence interval; CV ϭ coefficient of variation; DSST ϭ Digit Symbol Substitution Test; eGFR ϭ estimated glomerular filtration rate; Health ABC ϭ Health, Aging and Body Composition; MDRD ϭ Modification of Diet in Renal Disease; NFT ϭ neurofibrillary tangle; OR ϭ odds ratio; RAGE ϭ receptor for advanced glycation end product; SE ϭ standard error.Mounting evidence suggests that diabetes increases risk for cognitive impairment and dementia, including Alzheimer disease (AD), 1 although the pathogenesis is unknown. Accumulation of advanced glycation end products (AGEs) in the brain is one possible mechanism linking diabetes to cognitive impairment. AGEs are a group of highly stable crosslinked products that form through a series of reactions between glucose and proteins. While AGEs form during normal aging, formation accele...

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Section: Resultsmentioning

confidence: 99%

Advanced glycation end product level, diabetes, and accelerated cognitive aging

Yaffe¹,

Lindquist²,

Schwartz³

et al. 2011

Neurology

129

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“…82 Lastly, Yaffe et al showed that community-resident elderly individuals with elevated levels of cystatin-C (an inhibitor of cysteine proteases that co-localizes with b-amyloid in the brain of patients with Alzheimer disease) had lower cognitive test scores and were more likely to experience a decline in cognitive function during a 7-year follow-up period-even after adjustment for vascular risk factors. 83 Despite the absence of brain MRI data, it is possible that cystatin-C has a direct effect on the risk of developing Alzheimer disease.…”

Section: Potential Causes Of Cognitive Impairment In Patients With Ckdmentioning

confidence: 99%

Cognitive Disorders and Dementia in CKD

Bugnicourt

Godefroy

Chillon

et al. 2013

Journal of the American Society of Nephrology

483

431

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Epidemiologic data suggest that individuals at all stages of CKD have a higher risk of developing cognitive disorders and dementia. This risk is generally explained by the high prevalence of both symptomatic and subclinical ischemic cerebrovascular lesions. However, other potential mechanisms, including direct neuronal injury by uremic toxins, could also be involved, especially in the absence of obvious cerebrovascular disease. We discuss the prevalence and characteristics of cognitive disorders and dementia in patients with CKD, brain imaging findings, and traditional and nontraditional risk factors. Understanding the pathophysiologic interactions between renal impairment and brain function is important in order to minimize the risk for future cognitive impairment.

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“…The Health ABC Study found an increased risk of cognitive impairment among 3,030 older adults if they had high levels of cystatin C. 49 In contrast, in men aged 70 and 77 years from the Uppsala Longitudinal Study of Adult Men, high levels of serum cystatin C were associated with a decreased risk of AD. 50 The Study of Osteoporotic Fractures in 1,332 elderly women found a U-shape association between cystatin C and cognitive impairment, but after adjustment for covariates, these associations were no longer significant.…”

Section: Continuedmentioning

confidence: 99%

Dementia risk in renal dysfunction

et al. 2017

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Objective: Renal dysfunction has been linked with increased risk for cognitive impairment and dementia, but studies are conflicting. For that reason, the aim of the present systematic review and meta-analysis is to summarize the best available evidence on the prospective association between potential markers of renal dysfunction and development of cognitive impairment or dementia.Methods: Medline, Embase, and Cochrane Database of Systematic Reviews were searched for potential publications until August 1, 2016. Studies were eligible if they fulfilled the following criteria: population-based study, prospective design, $100 participants, aged $45 years, $1 year follow-up, and cognition/dementia outcomes. Where appropriate, random effects meta-analyses were conducted yielding pooled odds ratios (OR) and 95% confidence intervals (CI).Results: Twenty-two out of 8,494 abstracts fulfilled the eligibility criteria. Sufficient evidence was found for albuminuria, mixed results for estimated glomerular filtration rate (eGFR), insufficient support for cystatin C, and tentative evidence for serum creatinine and creatinine clearance. Meta-analyses of 5 studies representing 27,805 persons showed a 35% increased risk of cognitive impairment or dementia in those with albuminuria (OR 1.35, 95% CI 1.06-1.73, p 5 0.015), whereas eGFR ,60 mL/min/1.73 m 2 showed no significant association (OR 1.28, 95% CI 0.99-1.65, p 5 0.063). No meta-analyses could be done for serum creatinine, creatinine clearance, or cystatin C. Conclusions:The overall evidence for an association between renal dysfunction and cognitive impairment or dementia is modest. Evidence suggests that albuminuria is associated with higher odds of developing cognitive impairment or dementia. Renal dysfunction has been considered a candidate risk factor for cognitive impairment and dementia.1-3 The kidneys and the brain, both being end organs, are susceptible to vascular damage due to broadly similar anatomic and hemodynamic features. 4 Chronic kidney disease (CKD) and dementia share a similar risk factor profile including hypertension, diabetes mellitus, or hyperlipidemia, and in both conditions a high prevalence of small vessel disease, silent brain infarcts, white matter pathology, and microbleeds was reported.2,3,5-8 Hence, several pathways may underlie the association between CKD and cognitive impairment, including shared vascular factors or a direct neurotoxic effect of uremia. 2,9 Worldwide, the number of people with dementia has increased.

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Cystatin C as a marker of cognitive function in elders: Findings from the health ABC study

Cited by 109 publications

References 18 publications

Advanced glycation end product level, diabetes, and accelerated cognitive aging

Advanced glycation end product level, diabetes, and accelerated cognitive aging

Cognitive Disorders and Dementia in CKD

Dementia risk in renal dysfunction

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