The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort
Open accessAbstract
Background: Numerous cross-sectional studies have related exposure to neurotropic infectious agents with cognitive dysfunction in older adults, however, the temporal sequence is uncertain. Methods: In a representative, well-characterized, population-based aging cohort, we determined whether the temporal trajectories of multiple cognitive domains are associated with exposure to cytomegalovirus (CMV), Herpes Simplex virus, type 1 (HSV-1), Herpes Simplex virus, type 2 (HSV-2), or Toxoplasma gondii (TOX). Complex attention, executive functions, memory, language, and visuospatial function were assessed annually for 5 years among consenting individuals. Study entry IgG antibody titers indexing exposure to each infectious agent were examined in relation to slopes of subsequent temporal cognitive decline using multiple linear regressions adjusted for potential confounders. Results: The IgG levels for HSV-2 were significantly associated with baseline cognitive domain scores (N=1022 participants). Further, the IgG levels for HSV-2, TOX, and CMV, but not HSV-1 were significantly associated with greater temporal cognitive decline that varied by type of infection. Conclusions: Exposure to CMV, HSV-2, or TOX is associated with cognitive deterioration in older individuals, independent of general age–related variables. An increased understanding of the role of infectious agents in cognitive decline may lead to new methods for its prevention and treatment.
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“HSV-2 seropositivity has also been associated with decreased memory performance, but appeared to be unrelated to global cognition and other cognitive domains, or the risk of all-cause dementia, AD, vascular dementia and other dementias [27,28].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [27]
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“Another study with more subjects confirmed IgG antibodies were related to a lack of normal memory score gains due to practice [27].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [27]
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“For example, IgM levels appears to be a more accurate predictor than IgG levels [27,31,32].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [27]
Experimental — accuracy not yet measuredIn the citing paper
“Mechanisms underlying viral pathogenesis in these conditions may include a direct viral effect or indirect mechanisms, such as inflammation, epigenetic changes, and hypercoagulable changes, that may impact on brain structure and function in healthy or in cognitively impaired individuals [6, 11–15].”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [15]
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Cites
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Human T Cell Aging and the Impact of Persistent Viral Infections
Fülöp, T., Larbi, A., & Pawelec, G. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00271 · Cited by 347
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The Influence of Latent Viral Infection on Rate of Cognitive Decline over 4 Years
Aiello, A. E., Haan, M. N., Blythe, L., Moore, K., Gonzalez, J. M., & Jagust, W. (2006) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2006.00796.x · Cited by 210
Herpes virus in Alzheimer's disease: relation to progression of the disease
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Self-citationItzhaki, R. F. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00202 · Cited by 202
Endochin-like quinolones are highly efficacious against acute and latent experimental toxoplasmosis
Doggett, J. S., Nilsen, A., Forquer, I., Wegmann, K. W., Jones‐Brando, L. V., Yolken, R. H., Bordón, C., Charman, S. A., Katneni, K., Schultz, T. L., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1208069109 · Cited by 189
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- Ganguli, 2014, Vascular risk factors and cognitive decline in a population sample, Alzheimer Dis Assoc Disord, 28, 9, 10.1097/WAD.0000000000000004 · DOI
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Herpes simplex virus: global infection prevalence and incidence estimates, 2016
James, C. R., Harfouche, M., Welton, N. J., Turner, K., Abu-Raddad, L. J., Gottlieb, S. L., & Looker, K. J. (2020) · Bulletin of the World Health Organization · doi:10.2471/blt.19.237149 · Cited by 842
The Infectious Etiology of Alzheimer’s Disease
Sochocka, M., Zwolińska, K., & Leszek, J. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170313122937 · Cited by 399
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Liu, E., Zhang, Y., & Wang, J. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00432-x · Cited by 241
The Possibility of an Infectious Etiology of Alzheimer Disease
Ashraf, G. M., Tarasov, V. V., Makhmutovа, A., Chubarev, V. N., Avila-Rodriguez, M., Bachurin, S. O., & Aliev, G. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1388-y · Cited by 175
Burgdorf, K. S., Trabjerg, B. B., Pedersen, M. G., Nissen, J., Banasik, K., Pedersen, O. B., Sørensen, E., Nielsen, K. R., Larsen, M. H., Erikstrup, C., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.01.026 · Cited by 169
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Metadata
- Authors
- Nimgaonkar, V. L., Yolken, R. H., Wang, T., Chang, C.-C. H., McClain, L., McDade, E., Snitz, B. E., & Ganguli, M.
- Affiliations
- Psychiatry
- Johns Hopkins University (US)
- Biostatistics
- Medicine
- University of Pittsburgh (US)
- Corresponding author
- Nimgaonkar, Vishwajit L.
- McClain, Lora
- Snitz, Beth E.
- ORCID
- Venue
- Alzheimer Disease & Associated Disorders
- Published
- 2016-07
- Volume
- 30
- Issue
- 3
- Pages
- 216-222
- ISSN
- 0893-0341 (ISSN-L)
- PMC
- PMC4919236
- OpenAlex
- W2316924861
- Cited by
- 109
- References
- 39
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 12 · 2023: 13 · 2022: 17 · 2021: 17 · 2020: 8 · 2019: 7 · 2018: 8 · 2017: 8 · 2016: 4
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alzheimer Disease & Associated Disorders (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG023651, P01AG020677, K07AG044395)
- National Institute of Mental Health (R01MH063480)
- Fogarty International Center (D43TW009114)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
- Keywords
- cognitive decline, neurotropic infection, cytomegalovirus, herpes simplex virus type 2, herpes simplex virus type 1, Toxoplasma gondii, IgG antibody titers, older adults, temporal trajectories, executive function, memory, visuospatial ability, aging cohort
- MeSH terms
- Aged, Aging, Antibodies, Viral, Cross-Sectional Studies, Female, Humans, Male, Neuropsychological Tests, Toxoplasma, Cohort Studies, Simplexvirus, Cognitive Dysfunction
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