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August 5, 2009
Letter to the Editor

Kidney function is associated with the rate of cognitive decline in the elderly

September 22, 2009 issue
73 (12) 920-927

Abstract

Objective: We tested the hypothesis that impaired kidney function in the elderly is associated with a more rapid rate of cognitive decline.
Methods: Baseline serum was used to calculate estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease formula, for 886 elderly without dementia participating in the Rush Memory and Aging Project, a prospective, observational cohort study. Kidney function was also dichotomized into impairment or no impairment based on eGFR < or ≥60 mL/min/1.73 m2. Structured cognitive testing was performed at baseline and at annual evaluations, using a battery of 19 cognitive tests summarized into global cognition and 5 cognitive domains.
Results: In mixed-effects models adjusted for age, sex, and education, a lower eGFR at baseline was associated with a more rapid rate of cognitive decline (estimate 0.0008, SE <0.001, p = 0.017). The increased rate of cognitive decline associated with a 15-mL/min/1.73 m2 lower eGFR at baseline (approximately 1 SD) was similar to the effect of being 3 years older at baseline. Impaired kidney function at baseline was associated with a more rapid rate of cognitive decline (estimate −0.028, SE <0.009, p = 0.003). The increased rate of cognitive decline associated with impaired kidney function at baseline was approximately 75% the effect of ApoE4 allele on the rate of cognitive decline. Baseline kidney function was associated with declines in semantic memory, episodic memory, and working memory but not visuospatial abilities or perceptual speed.
Conclusion: Impaired kidney function is associated with a more rapid rate of cognitive decline in old age.

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REFERENCES

1.
Zhang QL, Koenig W, Raum E, Stegmaier C, Brenner H, Rothenbacher D. Epidemiology of chronic kidney disease: results from a population of older adults in Germany. Prev Med 2009;48:122–127.
2.
Duru OK, Vargas RB, Kermah D, Nissenson AR, Norris KC. High prevalence of stage 3 chronic kidney disease in older adults despite normal serum creatinine. J Gen Intern Med 2009;24:86–92.
3.
Anavekar NS, McMurray JJV, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004;351:1285–1295.
4.
Tsagalis G, Akrivos T, Alevizaki M, et al. Renal dysfunction in acute stroke: an independent predictor of long-term all combined vascular events and overall mortality. Nephrol Dial Transplant 2009;24:194–200.
5.
Koren-Morag N, Goldbourt U, Tanne D. Renal dysfunction and risk of ischemic stroke or TIA in patients with cardiovascular disease. Neurology 2006;67:224–228.
6.
Ovbiagele B. Impairment in glomerular filtration rate or glomerular filtration barrier and occurrence of stroke. Arch Neurol 2008;65:934–938.
7.
Hailpern SM, Melamed ML, Cohen HW, Hostetter TH. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III). J Am Soc Nephrol 2007;18:2205–2213.
8.
Kurella TM, Wadley V, Yaffe K, et al. Kidney function and cognitive impairment in us adults: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Am J Kidney Dis 2008;52:227–234.
9.
Barzilay JI, Fitzpatrick AL, Luchsinger J, et al. Albuminuria and dementia in the elderly: a community study. Am J Kidney Dis 2008;52:216–226.
10.
Kurella M, Chertow GM, Fried LF, et al. Chronic kidney disease and cognitive impairment in the elderly: the Health, Aging, and Body Composition Study. J Am Soc Nephrol 2005;16:2127–2133.
11.
Slinin Y, Paudel ML, Ishani A, et al. Kidney function and cognitive performance and decline in older men. J Am Geriatr Soc 2008;56:2082–2088.
12.
Bennett DA, Schneider JA, Buchman AS, Mendes de Leon C, Bienias JL, Wilson RS. The Rush Memory and Aging Project: study design and baseline characteristics of the study cohort. Neuroepidemiology 2005;25:163–175.
13.
Wilson RS, Barnes LL, Krueger KR, Hoganson G, Bienias JL, Bennett DA. Early and late life cognitive activity and cognitive systems in old age. J Int Neuropsychol Soc 2005;11:400–407.
14.
Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA. Mild cognitive impairment: risk of Alzheimer disease and rate of cognitive decline. Neurology 2006;67:441–445.
15.
Brosius FC III, Hostetter TH, Kelepouris E, et al. Detection of chronic kidney disease in patients with or at increased risk of cardiovascular disease: a science advisory from the American Heart Association Kidney and Cardiovascular Disease Council; the Councils on High Blood Pressure Research, Cardiovascular Disease in the Young, and Epidemiology and Prevention; and the Quality of Care and Outcomes Research Interdisciplinary Working Group—developed in collaboration with the National Kidney Foundation. Circulation 2006;114:1083–1087.
16.
Levey AS, Eckardt K-U, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005;67:2089–2100.
17.
Shah RC, Wilson RS, Tang Y, Dong X, Murray A, Bennett DA. Relation of hemoglobin to level of cognitive function in older persons. Neuroepidemiology 2009;32:40–46.
18.
Wilson RS, Krueger KR, Arnold SE, et al. Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry 2007;64:234–240.
19.
Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982;38:963–974.
20.
Collett D. Modelling Survival Data in Medical Research.
21.
SAS/STAT® User’s Guide, Version
22.
Manjunath G, Tighiouart H, Coresh J, et al. Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003;63:1121–1129.
23.
Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003;41:1–12.
24.
Rifkin DE, Shlipak MG, Katz R, et al. Rapid kidney function decline and mortality risk in older adults. Arch Intern Med 2008;168:2212–2218.
25.
Murray AM, Tupper DE, Knopman DS, et al. Cognitive impairment in hemodialysis patients is common. Neurology 2006;67:216–223.
26.
Murray AM. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv Chronic Kidney Dis 2008;15:123–132.
27.
Seliger SL, Siscovick DS, Stehman-Breen CO, et al. Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study. J Am Soc Nephrol 2004;15:1904–1911.
28.
Glassock RJ, Winearls C. An epidemic of chronic kidney disease: fact or fiction? Nephrol Dials Transplant 2008;23:1117–1121.
29.
Verhave JC, Fesler P, Ribstein J, du Cailar G, Mimran A. Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index. Am J Kidney Dis 2005;46:233–241.
30.
Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002;346:476–483.
31.
Das RR, Seshadri S, Beiser AS, et al. Prevalence and correlates of silent cerebral infarcts in the Framingham offspring study. Stroke 2008;39:2929–2935.
32.
Yaffe K, Lindquist K, Penninx BW, et al. Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 2003;61:76–80.
33.
Duron E, Hanon O. Vascular risk factors, cognitive decline, and dementia. Vasc Health Risk Manag 2008;4:363–381.
34.
Schneider JA, Boyle PA, Arvanitakis Z, Bienias JA, Bennett DA. Subcortical infarcts, Alzheimer’s disease pathology, and memory function in older persons. Ann Neurol 2007;62:59–66.
35.
Khatri M, Wright CB, Nickolas TL, et al. chronic kidney disease is associated with white matter hyperintensity volume: the Northern Manhattan Study (NOMAS). Stroke 2007;38:3121–3126.
36.
Kobayashi M, Hirawa N, Yatsu K, et al. Relationship between silent brain infarction and chronic kidney disease. Nephrol Dial Transplant 2009;24:201–207.
37.
Denny SD, Kuchibhatla MN, Cohen HJ. Impact of anemia on mortality, cognition, and function in community-dwelling elderly. Am J Med 2006;119:327–334.
38.
Kaindl AM, Sifringer M, Koppelstaetter A, et al. Erythropoietin protects the developing brain from hyperoxia-induced cell death and proteome changes. Ann Neurol 2008;64:523–534.
39.
Papageorgiou SG, Christou Y, Kontaxis T, et al. Dementia as presenting symptom of primary hyperparathyroidism: favourable outcome after surgery. Clin Neurol Neurosurg 2008;110:1038–1040.
Letters to the Editor
29 January 2010
Reply from the authors
Aron S. Buchman, MD, Rush University Medical Center
Raj J. Shah, MD, Patricia A. Boyle, PhD, David A. Bennett, MD

We thank Dr. Menkes for his interest in our article. [1] He raises an important question regarding the biologic mechanisms linking kidney function to cognitive decline.

The author hypothesizes that altered potassium metabolism may represent one potential mechanism. We found that the association between glomerular filtration rate (GFR) and cognitive decline remained significant when we considered the use of thiazide diuretics (Time * GFR: Estimate 0.0008 [S.E., 0.0003, p=0.011]).

In addition, the association between GFR and the rate of cognitive decline did not vary between participants based on the use thiazide diuretics (Time * GFR* Thiazide: Estimate -0.0005 [S.E., 0.0009, p=0.616]).

We have serum potassium levels and hope to have the opportunity to examine their relation to cognitive decline in the future.

Disclosure: Dr. Buchman receives research support from the NIH [R01AG17917 (Coinvestigator), P30AG10161 (Coinvestigator), and R01AG24480 (PI)]. Dr. Shah was a consultant with Paragon Biomedical, Inc.; served on the speakers' bureau for Eisai, Inc.; receives research support as Site PI or Site Subinvestigator from Ceregene, Inc., Danone Research B.V., Eisai, Inc., Elan Pharmaceuticals, Inc., Merck & Co., Inc., Pamlab, L.L.C., Pfizer, Inc., and Takeda Global Research & Development Center, Inc.; and receives research support from the NIH [P30 AG101061 (Education and Information Transfer Core Leader), P01 AG009466 (Coinvestigator, Administrative Core), R01NR009543 (Coinvestigator), R01 AG11101 (Coinvestigator), and U01 AG010483 (Site Investigator)] and from the Illinois Department of Public Aid Alzheimer's Disease Assistance Center. Dr. Boyle reports no disclosures. Dr. Bennett serves on the editorial board of Neurology; has received honoraria for non–industry-sponsored lectures; serves/has served as a consultant to EPIX Pharmaceuticals, Inc., Myriad Pharmaceuticals, Inc., Abbott Laboratories, Krog & Partners, Navigant Consulting, Inc., Partner Fund Management, LP, MFS Investment Management, UBS Global Asset Management, Schering Plough, Double Helix Development, Medivation, and Olson Research Group; and receives research support from Ceregene Inc., the NIH [P30AG10161 (PI), R01AG17917 (PI), R01AG15819 (PI), and R01AG24480 (Co-PI)], the Illinois Department of Public Health (PI), and the Robert C. Borwell Endowment Fund (PI).

29 January 2010
Kidney function is associated with the rate of cognitive decline in the elderly
Daniel L. Menkes, University of Connecticut Health Center

Buchman et al. demonstrate an inverse correlation between kidney function and cognition in the elderly. [1] The authors do not indicate whether the serum potassium concentrations in these patients show the same correlation.

Nerve excitability techniques allow for modeling of the ion channels within the peripheral nerve and their responses in particular disease states. [2] A nerve excitability study demonstrated that nerve dysfunction in nine patients with uremic neuropathy could be explained by increased extracellular potassium leading to changes in membrane excitability. [3]

Compared to normal controls, these patients had reduced superexcitability, increased accommodation to depolarizing and hyperpolarizing currents, and a steeper current current-threshold relationship. These changes are similar to those observed with nerve ischemia. Lowering the serum potassium by dialysis significantly reversed these effects. This model would predict that potassium levels would correlate with potassium ion channel dysfunction within the nervous system.

Do the authors have data regarding the correlation of serum potassium with the degree of cognitive impairment? As a corollary, did they note that patients using thiazide diuretics to treat hypertension had less cognitive impairment than those treated with other agents?

References

1. Buchman AS, Tanne D, Boyle PA, Shah RC, Leurgans SE, Bennett DA. Kidney function is associated with the rate of cognitive decline in the elderly. Neurology 2009;73:920-927.

2. Bostock H, Cikurel K, Burke D. Threshold tracking techniques in the study of human peripheral nerve. Muscle Nerve 1998;21:137-158.

3. Kiernan MC, Walters RJ, Andersen KV, Taube D, Murray NM, Bostock H. Nerve excitability changes in chronic renal failure indicate membrane depolarization due to hyperkalemia. Brain 2002;125:1366-1378.

Disclosure: Dr. Menkes served on the speakers' bureau of Eli Lilly Company; received travel expenses and honoraria for speaking on behalf of the use of duloxetine for the FDA approved indications of diabetic peripheral neuropathic pain and fibromyalgia; received honoraria from the American Association of Electrodiagnostic Medicine; received honoraria from the American Clinical Neurophysiology Society; performs EMG studies in his clinical practice that accounts for 50% of his time as a faculty member at the University of Connecticut Health Center; received discount on a quantitative testing device from Altus Research Inc. known as the Neurometer Sensory CPT; prepared affidavits on behalf of the Bayer Corporation and received compensation for the written affidavits.

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Published In

Neurology®
Volume 73Number 12September 22, 2009
Pages: 920-927
PubMed: 19657107

Publication History

Published online: August 5, 2009
Published in print: September 22, 2009

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Authors

Affiliations & Disclosures

A. S. Buchman, MD
From the Rush Alzheimer’s Disease Center (A.S.B., P.A.B., R.C.S., S.E.L., D.A.B.), Department of Neurological Sciences (A.S.B., S.E.L., D.A.B.), Department of Behavioral Science (P.A.B.), and Department of Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Department of Neurology (D.T.), Sheba Medical Center, Tel Hashomer, Israel.
D. Tanne, MD
From the Rush Alzheimer’s Disease Center (A.S.B., P.A.B., R.C.S., S.E.L., D.A.B.), Department of Neurological Sciences (A.S.B., S.E.L., D.A.B.), Department of Behavioral Science (P.A.B.), and Department of Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Department of Neurology (D.T.), Sheba Medical Center, Tel Hashomer, Israel.
P. A. Boyle, PhD
From the Rush Alzheimer’s Disease Center (A.S.B., P.A.B., R.C.S., S.E.L., D.A.B.), Department of Neurological Sciences (A.S.B., S.E.L., D.A.B.), Department of Behavioral Science (P.A.B.), and Department of Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Department of Neurology (D.T.), Sheba Medical Center, Tel Hashomer, Israel.
R. C. Shah, MD
From the Rush Alzheimer’s Disease Center (A.S.B., P.A.B., R.C.S., S.E.L., D.A.B.), Department of Neurological Sciences (A.S.B., S.E.L., D.A.B.), Department of Behavioral Science (P.A.B.), and Department of Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Department of Neurology (D.T.), Sheba Medical Center, Tel Hashomer, Israel.
S. E. Leurgans, PhD
From the Rush Alzheimer’s Disease Center (A.S.B., P.A.B., R.C.S., S.E.L., D.A.B.), Department of Neurological Sciences (A.S.B., S.E.L., D.A.B.), Department of Behavioral Science (P.A.B.), and Department of Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Department of Neurology (D.T.), Sheba Medical Center, Tel Hashomer, Israel.
D. A. Bennett, MD
From the Rush Alzheimer’s Disease Center (A.S.B., P.A.B., R.C.S., S.E.L., D.A.B.), Department of Neurological Sciences (A.S.B., S.E.L., D.A.B.), Department of Behavioral Science (P.A.B.), and Department of Family Medicine (R.C.S.), Rush University Medical Center, Chicago, IL; and Department of Neurology (D.T.), Sheba Medical Center, Tel Hashomer, Israel.

Notes

Address correspondence and reprint requests to Dr. Aron S. Buchman, Rush Alzheimer’s Disease Center, Rush University Medical Center, Armour Academic Facility, Suite 1038, 600 South Paulina St., Chicago, IL 60612 [email protected]

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