Relationship between homocysteine and cognitive impairment in elderly patients with chronic kidney disease
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Geriatrics and Gerontology Department, Faculty of Medicine, Helwan University, Helwan, EGYPT
Geriatrics and Gerontology Department, Faculty of Medicine, Ain Shams University, Cairo, EGYPT
Clinical Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, EGYPT
Online publication date: 2023-03-03
Publication date: 2023-05-01
Electron J Gen Med 2023;20(3):em476
To investigate the association of serum homocysteine levels with cognitive function in elderly patients with chronic kidney disease (CKD).

A case-control study on 200 elderlies >60 years who were distributed into two groups: group 1 (cases): 100 patients with CKD and group 2 (controls): 100 subjects who do not have CKD. All subjects undergo comprehensive geriatric assessment, cognitive assessment, and biochemical investigations including serum homocysteine.

The odds ratio of having impaired clinical dementia rating scores is 3.1 for CKD cases compared to controls. CKD patients have almost 3 times the risk of having cognitive impairment [OR=3.1; 95% CI (1.6-6.0)]. The mean serum homocysteine (18.2 μmol/L) among CKD showed a highly statistically significance compared to controls (10.1 μmol/L). Performance of multiple cognitive domains was reduced in association with elevated homocysteine levels. By using linear regression model for the factors independently related to cognitive performance among studied CKD cases, it was found that diabetes mellitus, educational level, age, and serum homocysteine level were strongly associated with consortium to establish a registry for Alzheimer’s disease neuropsychological battery total scores. Respecting the percentage variance explained by each significant variable (R2), serum homocysteine level is an independent significant variable predictor with the total scores.

The main features of cognitive impairment in CKD patients are executive dysfunction and memory impairment. Poor cognitive function in CKD patients was related with a higher homocysteine level independently.

Li N, Chen L, Muh RW, Li PL. Hyperhomocysteinemia associated with decreased renal transsulfuration activity in Dahl S rats. Hypertension. 2006;47(6):1094-100. https://doi.org/10.1161/01.HYP... PMid:16636197.
Kamat PK, Kalani A, Givvimani S, Sathnur PB, Tyagi SC, Tyagi N. Hydrogen sulfide attenuates neurodegeneration and neurovascular dysfunction induced by intracerebral-administered homocysteine in mice. Neuroscience. 2013;252:302-19. https://doi.org/10.1016/j.neur... PMid:23912038 PMCid:PMC3905452.
Zhuo JM, Wang H, Praticò D. Is hyperhomocysteinemia an Alzheimer’s disease (AD) risk factor, an AD marker, or neither? Trends Pharmacol Sci. 2011;32(9):562-71. https://doi.org/10.1016/j.tips... PMid:21684021 PMCid:PMC3159702.
Bonetti F, Brombo G, Magon S, Zuliani G. Cognitive status according to homocysteine and B-group vitamins in elderly adults. J Am Geriatr Soc. 2015;63(6):1158-63. https://doi.org/10.1111/jgs.13... PMid:26031567.
Shehata AS. Prevalence of depression among Egyptian geriatric community [Master’s thesis] Cairo: Ain Shams University; 1998.
Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The index of adl: A standardized measure of biological and psychosocial function. JAMA. 1963;185:914-9. https://doi.org/10.1001/jama.1... PMid:14044222.
El-Sherpiny M, Mortagy, A, Fahmy, H. Prevalence of hypercholesterolemia among elderly people living in elderly homes in Cairo. Cairo: Geriatric Department Library, Ain Shams University; 2000.
Morris JC, Heyman A, Mohs RC, et al. The consortium to establish a registry for Alzheimer’s disease (CERAD). Part I. Clinical and neuropsychological assessment of Alzheimer’s disease. Neurology. 1989;39(9):1159-65. https://doi.org/10.1212/WNL.39... PMid:2771064.
Elokl M. The Arabic version of the CERAD neuropsychological forms including the MMSE. Int Psychogeriatr. 2011;23(S1):139-400.
Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993 43(11):2412-4. https://doi.org/10.1212/WNL.43... PMid:8232972.
Perneczky R, Hartmann J, Grimmer T, Drzezga A, Kurz A. Cerebral metabolic correlates of the clinical dementia rating scale in mild cognitive impairment. J Geriatr Psychiatry Neurol. 2007;20(2):84-8. https://doi.org/10.1177/089198... PMid:17548777.
Benton AL, Hamsher K. Multilingual aphasia examination. Iowa City: University of Iowa Press; 1976.
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-98. https://doi.org/10.1016/0022-3... PMid:1202204.
Atkinson RC, Shiffrin RM. The control of short-term memory. Sci Am. 1971;225(2):82-90. https://doi.org/10.1038/scient... PMid:5089457.
Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer’s disease. Am J Psychiatry. 1984;141(11):1356-64. https://doi.org/10.1176/ajp.14... PMid:6496779.
Chandler MJ, Lacritz LH, Hynan LS, et al. A total score for the CERAD neuropsychological battery. Neurology. 2005;65(1):102-6. https://doi.org/10.1212/01.wnl... PMid:16009893.
Durga J, van Boxtel MP, Schouten EG, et al. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: A randomised, double blind, controlled trial. Lancet. 2007;369(9557):208-16. https://doi.org/10.1016/S0140-... PMid:17240287.
KDIGO. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;3(1):1-150.
Kurella Tamura M, Yaffe K, Hsu CY, et al. Cognitive impairment and progression of CKD. Am J Kidney Dis. 2016;68(1):77-83. https://doi.org/10.1053/j.ajkd... PMid:26972681 PMCid:PMC4921255.
Murray AM, Knopman DS. Cognitive impairment in CKD: No longer an occult burden. Am J Kidney Dis. 2010;56(4):615-8. https://doi.org/10.1053/j.ajkd... PMid:20851318 PMCid:PMC2943494.
Fratoni V, Brandi ML. B vitamins, homocysteine and bone health. Nutrients. 2015;7(4):2176-92. https://doi.org/10.3390/nu7042... PMid:25830943 PMCid:PMC4425139.
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(7):476-83. https://doi.org/10.1056/NEJMoa... PMid:11844848.
Francis ME, Eggers PW, Hostetter TH, Briggs JP. Association between serum homocysteine and markers of impaired kidney function in adults in the United States. Kidney Int. 2004;66(1):303-12. https://doi.org/10.1111/j.1523... PMid:15200438.
Helmer C, Stengel B, Metzger M, et al. Chronic kidney disease, cognitive decline, and incident dementia: The 3C study. Neurology. 2011;77(23):2043-51. https://doi.org/10.1212/WNL.0b... PMid:22116945.
Yeh YC, Huang MF, Hwang SJ, et al. Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease. Int J Geriatr Psychiatry. 2016;31(7):723-30. https://doi.org/10.1002/gps.43... PMid:26553116.
Kronenberg G, Colla M, Endres M. Folic acid, neurodegenerative and neuropsychiatric disease. Curr Mol Med. 2009;9(3):315-23. https://doi.org/10.2174/156652... PMid:19355913.
Viggiano D, Wagner CA, Blankestijn PJ, et al. Mild cognitive impairment and kidney disease: Clinical aspects. Nephrol Dial Transplant. 2020;35(1):10-7.
den Heijer T, Vermeer SE, Clarke R, et al. Homocysteine and brain atrophy on MRI of non-demented elderly. Brain. 2003;126(Pt 1):170-5. https://doi.org/10.1093/brain/... PMid:12477704.
Feng L, Isaac V, Sim S, Ng TP, Krishnan KR, Chee MW. Associations between elevated homocysteine, cognitive impairment, and reduced white matter volume in healthy old adults. Am J Geriatr Psychiatry. 2013;21(2):164-72. https://doi.org/10.1016/j.jagp... PMid:23343490.
Kinoshita M, Numata S, Tajima A, Shimodera S, Imoto I, Ohmori T. Plasma total homocysteine is associated with DNA methylation in patients with schizophrenia. Epigenetics. 2013;8(6):584-90. https://doi.org/10.4161/epi.24... PMid:23774737 PMCid:PMC3857338.
Hengstermann S, Laemmler G, Hanemann A, et al. Total serum homocysteine levels do not identify cognitive dysfunction in multimorbid elderly patients. J Nutr Health Aging. 2009;13(2):121-6. https://doi.org/10.1007/s12603... PMid:19214340.
Ozmen B, Ozmen D, Turgan N, Habif S, Mutaf I, Bayindir O. Association between homocysteinemia and renal function in patients with type 2 diabetes mellitus. Ann Clin Lab Sci. 2002;32(3):279-86.
Sonoda M, Shoji T, Kuwamura Y, et al. Plasma homocysteine and cerebral small vessel disease as possible mediators between kidney and cognitive functions in patients with diabetes mellitus. Sci Rep. 2017;7(1):4382. https://doi.org/10.1038/s41598... PMid:28663544 PMCid:PMC5491495.
Cianciolo G, De Pascalis A, Di Lullo L, Ronco C, Zannini C, La Manna G. Folic acid and homocysteine in chronic kidney disease and cardiovascular disease progression: Which comes first? Cardiorenal Med. 2017;7(4):255-66. https://doi.org/10.1159/000471... PMid:29118764 PMCid:PMC5662962.
Viroonudomphol D, Kajanachumpol S, Prawettongsopon C. Homocysteine and cognitive impairment in Thai elderly. World J Eng Technol. 2016;04(04):562-71. https://doi.org/10.4236/wjet.2....