Association between Cytomegalovirus Antibody Levels and Cognitive Functioning in Non-Elderly Adults

Background Elevated levels of antibodies to Cytomegalovirus (CMV) have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established. Methods We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50th, 75th, and 90th percentile of the group. Results Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient −1.03, p<.0002), Delayed Memory (coefficient −0.94, p<.001), Visuospatial/Constructional (coefficient −1.77, p<5×10−7), and Letter Number Sequencing (coefficient −0.15, p<.03). There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95th % CI 1.01, 2.64; p<.045), 2.22 (95th % CI 1.33, 3.70; p<.002), and 2.46 (95th % CI 1.24, 4.86; p<.010) with a CMV antibody level greater than or equal to the 50th, 75th, and 90th percentile respectively. Conclusions Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an improvement in cognitive functioning in otherwise healthy adults.

[1]  J. Dowd,et al.  Persistent viral pathogens and cognitive impairment across the life course in the third national health and nutrition examination survey. , 2014, The Journal of infectious diseases.

[2]  C. Söderberg-Nauclér Treatment of cytomegalovirus infections beyond acute disease to improve human health , 2014, Expert review of anti-infective therapy.

[3]  N. Inoue,et al.  Detection of human herpesviruses in the cerebrospinal fluid from patients diagnosed with or suspected of having progressive multifocal leukoencephalopathy , 2013, BMC Neurology.

[4]  I. Deary,et al.  Seropositivity for CMV and IL-6 levels are associated with grip strength and muscle size in the elderly , 2013, Immunity & Ageing.

[5]  I. Deary,et al.  Cytomegalovirus infection and cognitive abilities in old age , 2013, Neurobiology of Aging.

[6]  R A Ophoff,et al.  Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci , 2013, Molecular Psychiatry.

[7]  C. Mendonca,et al.  Cytomegalovirus encephalitis in an immunocompetent child: a sceptic diagnosis , 2012, BMJ Case Reports.

[8]  David Q. Beversdorf,et al.  Inflammation and reactivation of latent herpesviruses in older adults , 2012, Brain, Behavior, and Immunity.

[9]  S. Elliott Congenital cytomegalovirus infection: an overview. , 2011, Infectious disorders drug targets.

[10]  Michael J. Taylor,et al.  Demographically corrected norms for African Americans and Caucasians on the Hopkins Verbal Learning Test–Revised, Brief Visuospatial Memory Test–Revised, Stroop Color and Word Test, and Wisconsin Card Sorting Test 64-Card Version , 2011, Journal of clinical and experimental neuropsychology.

[11]  M. Cannon,et al.  Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  F. Dickerson,et al.  Association between cognitive functioning, exposure to Herpes Simplex Virus type 1, and the COMT Val158Met genetic polymorphism in adults without a psychiatric disorder , 2008, Brain, Behavior, and Immunity.

[13]  N. Lurain,et al.  Introduction to the special issue dedicated to the 11th International CMV and Beta Herpesvirus Workshop. , 2008, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[14]  W. Flanders,et al.  Seroprevalence of cytomegalovirus infection in the United States, 1988-1994. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  W. Jagust,et al.  The Influence of Latent Viral Infection on Rate of Cognitive Decline over 4 Years , 2006, Journal of the American Geriatrics Society.

[16]  P. Griffiths Cytomegalovirus infection of the central nervous system. , 2004, Herpes : the journal of the IHMF.

[17]  F. Dickerson,et al.  Association of serum antibodies to herpes simplex virus 1 with cognitive deficits in individuals with schizophrenia. , 2003, Archives of general psychiatry.

[18]  R. Yolken,et al.  Maternal infections and subsequent psychosis among offspring. , 2001, Archives of general psychiatry.

[19]  L. Wecker,et al.  Neonatal cytomegalovirus exposure decreases prepulse inhibition in adult rats: Implications for schizophrenia , 1999, Journal of neuroscience research.

[20]  C. Randolph,et al.  The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. , 1998, Journal of clinical and experimental neuropsychology.

[21]  S. Chou,et al.  Neutralizing antibody responses to reinfecting strains of cytomegalovirus in transplant recipients. , 1989, The Journal of infectious diseases.

[22]  J. Bale,et al.  Survival of cytomegalovirus in paper diapers and saliva , 1986, Pediatric infectious disease.

[23]  Mary L. Kumar Cytomegalovirus Infections , 1979, Southern medical journal.

[24]  M. Mcvoy,et al.  Cytomegalovirus vaccines. , 2013, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  Proceedings of the 11th International CMV and Beta Herpesvirus Workshop. May 13-17, 2007. Toulouse, France. , 2008, Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology.

[26]  J. J. Ryan,et al.  Wechsler Adult Intelligence Scale-III , 2001 .

[27]  R. Heaton Wisconsin Card Sorting Test manual , 1993 .

[28]  Robert K. Heaton,et al.  Wisconsin Card Sorting Test Manual – Revised and Expanded , 1993 .

[29]  N. Schmidt,et al.  Humoral immune response to virions and dense bodies of human cytomegalovirus determined by enzyme immunofluorescence assay , 1980, Journal of medical virology.