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The Influence of Latent Viral Infection on Rate of Cognitive Decline over 4 Years
Open accessAbstract
OBJECTIVES: To examine whether cytomegalovirus (CMV) and herpes simplex virus type‐1 (HSV‐1) are associated with cognitive decline over a 4‐year period and to assess whether C‐reactive protein (CRP) modifies these relationships. DESIGN: Prospective cohort study over a 4‐year period. SETTING: Community‐dwelling elderly population. PARTICIPANTS: The sample was a subset (1,204/1,789) of participants in the Sacramento Area Latino Study on Aging (SALSA) aged 60 to 100. MEASUREMENTS: Participants were screened annually over a 4‐year period for cognitive function and episodic memory. Cognitive function was assessed using the modified Mini‐Mental State Examination, and episodic memory was assessed using a word list‐learning test of delayed recall. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV‐1 and for levels of CRP. RESULTS: There was a significantly higher rate of cognitive decline over the 4‐year period in subjects with the highest CMV antibody levels at baseline than in individuals with the lowest levels (β=−0.053, standard error =0.018; P =.003), after controlling for age, sex, education, income, and chronic health conditions. There was no association between HSV‐1 antibody levels and cognitive decline. CRP did not modify the relationship between viral antibody levels and cognitive decline. CONCLUSION: This is the first study to show that individuals with higher levels of antibody to CMV experience a more‐rapid rate of cognitive decline than those with lower levels. Understanding the mechanisms by which CMV influences cognition may aid development of intervention strategies targeting infection, viral reactivation, and immune response over the life course.
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“According to the ‘viral hypothesis of AD’, this interaction may be non-specifically associated with up-regulation of inflammatory responses and oxidative stress, which are secondary, but relevant components of the amyloid cascade.”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [12]
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“Similarly, in older participants of Latin American descent in the SALSA study in the United States [55], those with the highest CMV antibody levels had more cognitive decline relative to the lowest levels.”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [55]
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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 [12]
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“This interaction may also operate through a specific mechanism within the core pathogenesis, hastening amyloid overproduction [10, 12].”
From Cognitive decline following acute viral infections: literature review and projections for post-COVID-19 (2022) · cites this paper as [12]
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Metadata
- Authors
- Aiello, A. E., Haan, M. N., Blythe, L., Moore, K., Gonzalez, J. M., & Jagust, W.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Aiello, Allison E.
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 2006-07
- Volume
- 54
- Issue
- 7
- Pages
- 1046-1054
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- OpenAlex
- W1946070691
- Cited by
- 210
- References
- 81
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 11 · 2022: 14 · 2021: 14 · 2020: 8 · 2019: 10 · 2018: 11 · 2017: 7 · 2016: 10 · 2015: 16 · 2014: 11 · 2013: 14 · 2012: 12
- FWCI
- 6.51
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- National Institutes of Health (DK20572)
- National Institute on Aging (AG-12975, R01AG012975, R03AG033751)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-60753, P60DK020572, NIH5P60, R01DK060753)
- Topics
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
- Keywords
- cytomegalovirus, herpes simplex virus type 1, viral latency, cognitive decline, C-reactive protein, immunoglobulin G antibodies, episodic memory, older adults, aging, viral reactivation, immune response
- MeSH terms
- Aged, Aged, 80 and over, Antibodies, Viral, C-Reactive Protein, California, Cognition Disorders, Cytomegalovirus Infections, Dose-Response Relationship, Immunologic, Female, Herpes Simplex, Humans, Immunoglobulin G, Male, Middle Aged, Prospective Studies, Time Factors, Effect Modifier, Epidemiologic, Mexican Americans, Herpesvirus 1, Human
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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