Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease
Yi-Chun Yeh
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorMei-Feng Huang
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorShang-Jyh Hwang
Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorJer-Chia Tsai
Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorTai-Ling Liu
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorShih-Ming Hsiao
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorYi-Hsin Yang
School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Mei-Chuan Kuo
Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Correspondence to: Mei-Chuan Kuo, M.D., M.S, E-mail: [email protected]; Cheng-Sheng Chen, M.D., Ph.D., E-mail: [email protected]Search for more papers by this authorCorresponding Author
Cheng-Sheng Chen
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Correspondence to: Mei-Chuan Kuo, M.D., M.S, E-mail: [email protected]; Cheng-Sheng Chen, M.D., Ph.D., E-mail: [email protected]Search for more papers by this authorYi-Chun Yeh
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorMei-Feng Huang
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorShang-Jyh Hwang
Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorJer-Chia Tsai
Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorTai-Ling Liu
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorShih-Ming Hsiao
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorYi-Hsin Yang
School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan
Search for more papers by this authorCorresponding Author
Mei-Chuan Kuo
Faculty of Renal Care, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Correspondence to: Mei-Chuan Kuo, M.D., M.S, E-mail: [email protected]; Cheng-Sheng Chen, M.D., Ph.D., E-mail: [email protected]Search for more papers by this authorCorresponding Author
Cheng-Sheng Chen
Department of Psychiatry, Kaohsiung Medical University, Kaohsiung, Taiwan
Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
Correspondence to: Mei-Chuan Kuo, M.D., M.S, E-mail: [email protected]; Cheng-Sheng Chen, M.D., Ph.D., E-mail: [email protected]Search for more papers by this authorAbstract
Objectives
Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD.
Methods
Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests.
Results
A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (β = −0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (β = −0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients.
Conclusions
This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd.
References
- Albert ML. 1973. A simple test of visual neglect. Neurology 23: 658–664.
- Benton AL, Hamsher KD. 1989. Multilingual Aphasia Examination. AJA Association: Iowa City.
- Brady CB, Gaziano JM, Cxypoliski RA, et al. 2009. Homocysteine lowering and cognition in CKD: the Veterans Affairs homocysteine study. Am J Kidney Dis 54: 440–449.
- Bugnicourt JM, Godefroy O, Chillon JM, Choukroun G, Massy ZA. 2013. Cognitive disorders and dementia in CKD: the neglected kidney–brain axis. J Am Soc Nephrol 24: 353–363.
- Buschke H, Fuld PA. 1974. Evaluating storage, retention, and retrieval in disordered memory and learning. Neurology 24: 1019–1025.
- Charlton RA, Lamar M, Ajilore O, Kumar A. 2014. Associations between vascular risk and mood in euthymic older adults: preliminary findings. Am J Geriatr Psychiatry 22: 936–945.
- Chen CS, Tsai JC, Tsang HY, et al. 2005. Homocysteine levels, MTHFR C677T genotype, and MRI Hyperintensities in late-onset major depressive disorder. Am J Geriatr Psychiatry 13: 869–875.
- Clarke R, Daly L, Robinson K, et al. 1991. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 324: 1149–1155.
- D'Agostino RB Sr, Vasan RS, Pencina MJ, et al. 2008. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 117: 743–753.
- Dirrichs T, Penzkofer T, Reinartz SD, et al. 2015. Extracoronary thoracic and coronary artery calcifications on chest CT for lung cancer screening: association with established cardiovascular risk factors—the “CT-risk” trial. Acad Radiol 22: 880–889.
- Dubois B, Slachevsky A, Litvan I, Pillon B. 2000. The FAB: a Frontal Assessment Battery at bedside. Neurology 55: 1621–1626.
- Elias MF, Elias PK, Seliger SL, et al. 2009. Chronic kidney disease, creatinine and cognitive functioning. Nephrol Dial Transplant 24: 2446–2452.
- Finkelstein JD. 1998. The metabolism of homocysteine: pathways and regulation. Eur J Pediatr 157(Suppl 2): S40–44.
- Francis ME, Eggers PW, Hostetter TH, Briggs JP. 2004. Association between serum homocysteine and markers of impaired kidney function in adults in the United States. Kidney Int 66: 303–312.
- Gorelick PB, Scuteri A, Black SE, et al. 2011. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42: 2672–2713.
- Helmer C, Stengel B, Metzger M, et al. 2011. Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study. Neurology 77: 2043–2051.
- Hogervorst E, Ribeiro HM, Molyneux A, Budge M, Smith AD. 2002. Plasma homocysteine levels, cerebrovascular risk factors, and cerebral white matter changes (leukoaraiosis) in patients with Alzheimer disease. Arch Neurol 59: 787–793.
- Kimmel PL, Thamer M, Richard CM, Ray NF. 1998. Psychiatric illness in patients with end-stage renal disease. Am J Med 105: 214–221.
- Kivimaki M, Shipley MJ, Allan CL, et al. 2012. Vascular risk status as a predictor of later-life depressive symptoms: a cohort study. Biol Psychiatry 72: 324–330.
- Kronenberg G, Colla M, Endres M. 2009. Folic acid, neurodegenerative and neuropsychiatric disease. Curr Mol Med 9: 315–323.
- Kurella Tamura M, Muntner P, Wadley V, et al. 2011. Albuminuria, kidney function, and the incidence of cognitive impairment among adults in the United States. Am J Kidney Dis 58: 756–763.
- Levey AS, Coresh J, Greene T, et al. 2007. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 53: 766–772.
- Lipton SA, Kim WK, Choi YB, et al. 1997. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A 94: 5923–5928.
- Madero M, Gul A, Sarnak MJ. 2008. Cognitive function in chronic kidney disease. Semin Dial 21: 29–37.
- Mattson MP. 2003. Methylation and acetylation in nervous system development and neurodegenerative disorders. Ageing Res Rev 2: 329–342.
- Mattson MP, Shea TB. 2003. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci 26: 137–146.
- Mogi M, Horiuchi M. 2011. Clinical interaction between brain and kidney in small vessel disease. Cardiol Res Pract 2011: 306189. doi: 10.4061/2011/306189.
- Murray AM. 2009. The brain and the kidney connection: a model of accelerated vascular cognitive impairment. Neurology 73: 916–917.
- Murray AM, Knopman DS. 2010. Cognitive impairment in CKD: no longer an occult burden. Am J Kidney Dis 56: 615–618.
- O'Brien JT, Erkinjuntti T, Reisberg B, et al. 2003. Vascular cognitive impairment. The Lancet. Neurology 2: 89–98.
- Obeid R, Herrmann W. 2006. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 580: 2994–3005.
- Radic J, Ljutic D, Radic M, et al. 2010. The possible impact of dialysis modality on cognitive function in chronic dialysis patients. Neth J Med 68: 153–157.
- Reitan R. 1978. Manual for Administration of Neuropsychological Test Batteries for Adults and Children. Reitan Neuropsychology Laboratories, Inc.: Tucson, AZ.
- Roman GC, Royall DR. 1999. Executive control function: a rational basis for the diagnosis of vascular dementia. Alzheimer Dis Assoc Disord 13(Suppl 3): S69–80.
- Sehgal AR, Grey SF, DeOreo PB, Whitehouse PJ. 1997. Prevalence, recognition, and implications of mental impairment among hemodialysis patients. Am J Kidney Dis 30: 41–49.
- Seliger SL, Siscovick DS, Stehman-Breen CO, et al. 2004. Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study. J Am Soc Nephrol 15: 1904–1911.
- Seshadri S, Beiser A, Selhub J, et al. 2002. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med 346: 476–483.
- Seshadri S, Wolf PA, Beiser AS, et al. 2008. Association of plasma total homocysteine levels with subclinical brain injury: cerebral volumes, white matter hyperintensity, and silent brain infarcts at volumetric magnetic resonance imaging in the Framingham Offspring Study. Arch Neurol 65: 642–649.
- Sheline YI, Barch DM, Garcia K, et al. 2006. Cognitive function in late life depression: relationships to depression severity, cerebrovascular risk factors and processing speed. Biol Psychiatry 60: 58–65.
- Stein JH, McBride PE. 1998. Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. off. Arch Intern Med 158: 1301–1306.
- Sunrise-Editors. 1995. Operating Insturctions for Sunrise Systmes: Continuous Performance Task. Sunrise Systems, Inc.: Washington.
- Temple ME, Luzier AB, Kazierad DJ. 2000. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother 34: 57–65.
- Tsai CF, Wang SJ, Fuh JL. 2010. Moderate chronic kidney disease is associated with reduced cognitive performance in midlife women. Kidney Int 78: 605–610.
- Wang F, Zhang L, Liu L, Wang H. 2010. Level of kidney function correlates with cognitive decline. Am J Nephrol 32: 117–121.
- Wechsler D. 1987. Wechsler Memory Scale-Revised (WMS-R) manual. The Psychological Corporation: San Antonio, TX.
- Yang AC, Tsai SJ, Yeh HL, et al. 2010. Association between renal function and cognitive performance in elderly community-dwelling men without dementia. J Am Geriatr Soc 58: 2046–2048.
- Yeh YC, Tsang HY, Lin PY, et al. 2011. Subtypes of mild cognitive impairment among the elderly with major depressive disorder in remission. Am J Geriatr Psychiatry 19: 923–931.
- Zigmond AS, Snaith RP. 1983. The hospital anxiety and depression scale. Acta Psychiatr Scand 67: 361–370.
