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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]
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“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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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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