Dysexecutive Performance of Elderly Patients with Chronic Hepatitis C Virus Infection

Tomader Taha Abdel Rahman, Marwa Abdel Azeem Abdel Guaad, Ahmad Kamel Mortagy

Department of Geriatrics Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

DOI: 10.4236/aar.2014.34037                

Abstract

Chronic infection with hepatitis C virus (HCV) is one of the most important causes of chronic liver disease, which can progress to cirrhosis and hepatocellular carcinoma (HCC). It is well established that advanced forms of the disease are accompanied by overt and global cognitive deficits (hepatic encephalopathy) but now there is a growing evidence that the alterations in cerebral function in patients with chronic HCV infection may appear long before the development of severe liver cirrhosis, it has been hypothesized that it is related to a direct effect of HCV on the brain; or the neurotoxic effect of HCV-related systemic inflammation. The purpose of the study was to assess the possible existence of executive dysfunction in chronic HCV infected patients. One hundred elderly patients aged 60 years and above agreed to participate in this study; 50 patients were HCV positive (cases) and 50 patients were HCV negative (controls). All participants were subjected to the following: diagnosis of HCV by detection of HCV antibodies using ELISA technique, non-invasive assessment of liver condition, and evaluation of executive functions using 5 neuropsychological tests. The study showed that there was a significant difference between cases and controls regarding 2 executive function tests related to the phonological loop component of working memory among HCV positive patients. The study concluded that chronic HCV infection is accompanied by dysexecutive performance.

Keywords

Elderly, Executive Functions, HCV

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Lauer, G.M. and Walker, B.D. (2001) Hepatitis C Virus Infection. New England Journal of Medicine, 345, 41-52. http://dx.doi.org/10.1056/NEJM200107053450107
[2]	Abdel-Wahab, M.F., Zakaria, S., Kamel, M., Abdel-Khaliq, M.K., Mabrouk, M.A., Salama, H., et al. (1994) High Seroprevalence of Hepatitis C Infection among Risk Groups in Egypt. The American Journal of Tropical Medicine and Hygiene, 51, 563-567.
[3]	Binesh, N., Huda, A., Thomas, M.A., Wyckoff, N., Bugbee, M., Han, S., et al. (2006) Hepatic Encephalopathy: A Neurochemical Neuroanatomical, and Neuropsychological Study. Journal of Applied Clinical Medical Physics, 7, 86-96. http://dx.doi.org/10.1120/jacmp.2027.25374
[4]	Pantiga, C., Rodrigo, L.R., Cuest, M., Lopez, L. and Arias, J.L. (2003) Cognitive Deficits in Patients with Hepatic Cirrhosis and in Liver Transplant Recipients. Journal of Neuropsychiatry and Clinical Neurosciences, 15, 84-89. http://dx.doi.org/10.1176/appi.neuropsych.15.1.84
[5]	Mattarozzi, K., Campi, C., Guarino, M. and Stracciari, A. (2005) Distinguishing between Clinical and Minimal Hepatic Encephalopathy on the Basis of Specific Cognitive Impairment. Metabolic Brain Disease, 20, 243-249. http://dx.doi.org/10.1007/s11011-005-7212-1
[6]	Forton, D.M., Thomas, H.C., Murphy, C.A., Allsop, J.M., Foster, G.R., Main, J., et al. (2002) Hepatitis C and Cognitive Impairment in a Cohort of Patients with Mild Liver Disease. Hepatology, 35, 433-439. http://dx.doi.org/10.1053/jhep.2002.30688
[7]	Back-Madruga, C., Fontana, R. and Bielauskas, L. (2003) Predictors of Cognitive Impairment in Chronic Hepatitis C Patients Entering the HALT-C Trial. Journal of the International Neuropsychological Society, 9, 245-246.
[8]	Collie, A. (2005) Cognition in Liver Disease. Liver International, 25, 1-8. http://dx.doi.org/10.1111/j.1478-3231.2005.01012.x
[9]	Hilsabeck, R.C., Perry, W. and Hassanein, T.I. (2002) Neuropsychological Impairment in Patients with Chronic Hepatitis C. Hepatology, 35, 440-446. http://dx.doi.org/10.1053/jhep.2002.31257
[10]	Karin, W., Martin, B., Jochen, K., Jochen, E. and Björn, A. (2005) Neurological and Neuropsychiatric Syndromes Associated with Liver Disease. AIDS, S3, 93-98.
[11]	McAndrews, M.P., Farcnik, K., Carlen, P., Damyanovich, A., Mrkonjic, M., Jones, S., et al. (2005) Prevalence and Significance of Neurocognitive Dysfunction in Hepatitis C in the Absence of Correlated Risk Factors. Hepatology, 41, 801-808. http://dx.doi.org/10.1002/hep.20635
[12]	American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders. 4th Edition, American Psychiatric Association, Washington DC, 135.
[13]	Carey, C.L., Kramer, J.H., Josephson, S.A., Mungas, D., Reed, B.R., Schuff, N., et al. (2008) Subcortical Lacunes Are Associated with Executive Dysfunction in Cognitively Normal Elderly. Stroke, 39, 397-402. http://dx.doi.org/10.1161/STROKEAHA.107.491795
[14]	Johnson, J.K., Lui, L.Y. and Yaffe, K. (2007) Executive Function, More Than Global Cognition, Predicts Functional Decline and Mortality in Elderly Women. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 62, 1134-1141.
[15]	American College of Radiology, Expert Panel on Gastrointestinal Imaging (2002) Liver Lesion Characterization. American College of Radiology, Reston.
[16]	Iacobellis, A., Fusilli, S., Mangia, A., Clemente, R., Festa, V., Giacobbe, A., et al. (2005) Ultrasonographic and Biochemical Parameters in the Non-Invasive Evaluation of Liver Fibrosis in Hepatitis C Virus Chronic Hepatitis. Alimentary Pharmacology Therapeutics, 22, 769-774.
[17]	Folstein, M.F., Folstein, S.E. and McHugh, P.R. (1975) “Mini-Mental State”: A Practical Method for Grading the Cognitive State of Patients for the Clinician. Journal of Psychiatric Research, 12, 189-198. http://dx.doi.org/10.1016/0022-3956(75)90026-6
[18]	Sheikh, J.A. and Yesavage, J.A. (1986) Recent Finding and Development of a Shorter Version. In: Brinn, T.L., Ed., Clinical Gerontology: A Guide to Assessment and Intervention, Hawarth Press, New York.
[19]	Wechsler, D. (1997) Wechsler Adult Intelligence Scale. 3rd Edition, Harcourt Assessment, San Antonio.
[20]	Borson, S., Brush, M., Gil, E., Scanlan, J., Vitaliano, P., Chen, J., et al. (1999) The Clock Drawing Test: Utility for Dementia Detection in Multiethnic Elders. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 54, 534-540. http://dx.doi.org/10.1093/gerona/54.11.M534
[21]	Brucki, S.M. and Rocha, M.S. (2004) Category Fluency Test: Effects of Age, Gender and Education on Total Scores, Clustering and Switching in Brazilian Portuguese-Speaking Subjects. Brazilian Journal of Medical and Biological Research, 37, 1771-1777.
[22]	Royall, D.R., Mahurin, R.K. and Gray, K. (1992) Bedside Assessment of Executive Cognitive Impairment: The Executive Interview (EXIT). Journal of the American Geriatrics Society, 40, 1221-1226.
[23]	Heaton, R.K. (1981) A Manual for the Wisconsin Card Sorting Test. Psychological Assessment Services, Odessa, FL.
[24]	Posner, M.I. and DiGirolamo, G.J. (1998) Executive Attention: Conflict, Target Detection and Cognitive Control. In: Parasuraman, R., Ed., The Attentive Brain, MIT Press, Cambridge.
[25]	Welsh, M.C., Satterlee-Cartmell, T. and Stine, M. (1999) Towers of Hanoi and London: Contribution of Working Memory and Inhibition to Performance. Brain and Cognition, 41, 231-242. http://dx.doi.org/10.1006/brcg.1999.1123
[26]	Lezak, M.D. (1995) Neuropsychological Assessment. 3rd Edition, Oxford University Press, Oxford.
[27]	Schillerstrom, J.E., Rickenbacker, D., Joshi, K.G., et al. (2009) Executive Function in Self-Neglecting Adult Protective Services Referrals Compared with Elder Psychiatric Outpatients. American Journal of Geriatric Psychiatry, 17, 907-910. http://dx.doi.org/10.1097/JGP.0b013e3181b4bf64
[28]	Forton, D.M., Allsop, J.M., Cox, I.J., Hamilton, G., Wesnes, K., Thomas, H.C., et al. (2005) A Review of Cognitive Impairment and Cerebral Metabolite Abnormalities in Patients with Hepatitis C Infection. AIDS, 19, 53-63. http://dx.doi.org/10.1097/01.aids.0000192071.72948.77
[29]	Forton, D.M., Thomas, H.C. and Taylor-Robinson, S.D. (2004) Central Nervous System Involvement in Hepatitis C Virus Infection. Metabolic Brain Disease, 19, 383-391. http://dx.doi.org/10.1023/B:MEBR.0000043983.42843.ac
[30]	Sun, X.W., Zhang, X.C., Chen, X.C., Zhang, P., Bao, M., Zhang, D.R., et al. (2005) Age-Dependent Brain Activation during Forward and Backward Digit Recall Revealed by fMRI. Neuroimage, 26, 36-47. http://dx.doi.org/10.1016/j.neuroimage.2005.01.022
[31]	Stokholm, J., Vogel, A., Gade, A. and Waldemar, G. (2005) The Executive Interview as a Screening Test for Executive Dysfunction in Patients with Mild Dementia. Journal of the American Geriatrics Society, 53, 1577-1581. http://dx.doi.org/10.1111/j.1532-5415.2005.53470.x
[32]	Alvarez, J. and Emory, E. (2006) Executive Function and the Frontal Lobes: A Meta-Analytic Review. Neuropsychology Review, 16, 17-42. http://dx.doi.org/10.1007/s11065-006-9002-x
[33]	Lezak, M.D., Howieson, D.B. and Loring, D.W. (2004) Neuropsychological Assessment. 4th Edition, Oxford University Press, New York.
[34]	Clark, L., Bechara, A., Damasio, H., Aitken, M.R.F., Sahakian, B.J., Robbins, T.W.L., et al. (2008) Differential Effects of Insular and Ventromedial Prefrontal Cortex Lesions on Risky Decision Making. Brain, 131, 1311-1322. http://dx.doi.org/10.1007/s11065-006-9002-x
[35]	Shokri-Kojori, E., Motes, M.A., Rypma, B. and Krawczyk, D.C. (2012) The Network Architecture of Cortical Processing in Visuo-Spatial Reasoning. Scientific Reports, 2, Article No. 411.
[36]	Leh, S.E., Petrides, M. and Strafella, A.P. (2010) The Neural Circuitry of Executive Functions in Healthy Subjects and Parkinson’s Disease. Neuropsychopharmacology, 35, 70-85. http://dx.doi.org/10.1038/npp.2009.88
[37]	Dirnberger, G., Frith, C.D. and Jahanshahi, M. (2005) Executive Dysfunction in Parkinson’s Disease Is Associated with Altered Pallidal-Frontal Processing. Neuroimage, 25, 588-599. http://dx.doi.org/10.1016/j.neuroimage.2004.11.023
[38]	Zgaljardic, D.J., Borod, J.C., Foldi, N.S., Mattis, P.J., Gordon, M.F., Feigin, A., et al. (2006) An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson’s Disease. Journal of Clinical and Experimental Neuropsychology, 28, 1127-1144. http://dx.doi.org/10.1080/13803390500246910
[39]	Fletcher, N.F. and McKeating, J.A. (2012) Hepatitis C Virus and the Brain. Journal of Viral Hepatitis, 19, 301-306. http://dx.doi.org/10.1111/j.1365-2893.2012.01591.x
[40]	Fishman, S.L., Murray, J.M., Eng, F.J., Walewski, J.L., Morgello, S. and Branch, A.D. (2008) Molecular and Bioinformatic Evidence of Hepatitis C Virus Evolution in Brain. The Journal of Infectious Diseases, 197, 597-607. http://dx.doi.org/10.1086/526519
[41]	Wilkinson, J., Radkowski, M., Eschbacher, J.M. and Laskus, T. (2010) Activation of Brain Macrophages/Microglia Cells in Hepatitis C Infection. Gut, 59, 1394-1400. http://dx.doi.org/10.1086/526519
[42]	Groth-Marnat, G. and Teal, M. (2000) Block Design as a Measure of Everyday Spatial Ability: A Study of Ecological Validity. Perceptual and Motor Skills, 90, 522-526. http://dx.doi.org/10.2466/pms.2000.90.2.522
[43]	Royall, D.R., Cordes, J.A. and Polk, M. (1998) CLOX: An Executive Clock Drawing Task. Journal of Neurology, Neurosurgery Psychiatry, 64, 588-594. http://dx.doi.org/10.1136/jnnp.64.5.588
[44]	Hilsabeck, R.C., Hassanein, T.I., Carlson, M.D., et al. (2003) Cognitive Functioning and Psychiatric Symptomatology in Patients with Chronic Hepatitis C. Journal of the International Neuropsychological Society, 9, 847-854. http://dx.doi.org/10.1136/jnnp.64.5.588
[45]	Prakash, R.S., Erickson, K.I., Colcombe, S.J., Kim, J.S., Voss, M.W. and Kramer, A.F. (2009) Age-Related Differences in the Involvement of the Prefrontal Cortex in Attentional Control. Brain and Cognition, 71, 328-335. http://dx.doi.org/10.1016/j.bandc.2009.07.005
[46]	Iavarone, A., Lorè, E., De Falco, C., Milan, G., Mosca, R., Pappatà, S., et al. (2011) Dysexecutive Performance of Healthy Oldest Old Subjects on the Frontal Assessment Battery. Aging Clinical and Experimental Research, 23, 351-356.
[47]	Schinka, J.A., Vanderploeg, R.D., Rogish, M., Graves, A.B., Mortimer, J.A. and Ordoric, P.I. (2002) Effects of the Use of Alcohol and Cigarettes on Cognition in Elderly Adults. Journal of the International Neuropsychological Society, 8, 811-818. http://dx.doi.org/10.1017/S135561770286009X
[48]	Chen, W.T., Wang, P.N., Wang, S.J., Fuh, J.L., Lin, K.N. and Liu, H.C. (2003) Smoking and Cognitive Performance in the Community Elderly: A Longitudinal Study. Journal of Geriatric Psychiatry and Neurology, 16, 18-22. http://dx.doi.org/10.1177/0891988702250510
[49]	Razani, J., Boone, K., Lesser, I. and Weiss, D. (2004) Effects of Cigarette Smoking History on Cognitive Functioning in Healthy Older Adults. The American Journal of Geriatric Psychiatry, 12, 404-411.
[50]	Reitz, C., Luchsinger, J., Tang, M.X. and Mayeux, R. (2005) Effect of Smoking and Time on Cognitive Function in the Elderly without Dementia. Neurology, 65, 870-875. http://dx.doi.org/10.1212/01.wnl.0000176057.22827.b7
[51]	Farias, S.T., Mungas, D., Hinton, L. and Haan, M. (2011) Demographic, Neuropsychological and Functional Predictors of Rate of Longitudinal Cognitive Decline in Hispanic Older Adults. The American Journal of Geriatric Psychiatry, 19, 440-450.
[52]	Souza Cde, O., Voos, M.C., Francato, D.V., Chien, H.F. and Barbosa, E.R. (2013) Influence of Educational Status on Executive Function and Functional Balance in Individuals with Parkinson Disease. Cognitive and Behavioral Neurology, 26, 6-13.