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Herpes Viruses in the Baltimore Longitudinal Study of Aging: Associations With Brain Volumes, Cognitive Performance, and Plasma Biomarkers
Duggan MR, Peng Z, An Y, Kitner Triolo MH, Shafer AT, Davatzikos C, Erus G, Karikkineth A et al.. Neurology, 2022-10-31
Topic: Brain proteins, microglia and lab models
Background and objectives Although an infectious etiology of Alzheimer disease (AD) has received renewed attention with a particular focus on herpes viruses, the longitudinal effects of symptomatic herpes virus (sHHV) infection on brain structure and cognition remain poorly understood, as does the effect of sHHV on AD/neurodegeneration biomarkers. Methods We used a longitudinal, community-based cohort to characterize the association of sHHV diagnoses with changes in 3 T MRI brain volume and cognitive performance. In addition, we related sHHV to cross-sectional differences in plasma biomarkers of AD (β-amyloid [Aβ] 42/40 ), astrogliosis (glial fibrillary acidic protein [GFAP]), and neurodegeneration (neurofilament light [NfL]). Baltimore Longitudinal Study of Aging participants were recruited from the community and assessed with serial brain MRIs and cognitive examinations over an average of 3.4 (SD = 3.2) and 8.6 (SD = 7.7) years, respectively. sHHV classification used International Classification of Diseases, Ninth Revision codes documented at comprehensive health and functional screening evaluations at each study visit. Linear mixed-effects and multivariable linear regression models were used in analyses. Results A total of 1,009 participants were included in the primary MRI analysis, 98% of whom were cognitively normal at baseline MRI (mean age = 65.7 years; 54.8% female). Having a sHHV diagnosis (N = 119) was associated with longitudinal reductions in white matter volume (annual additional rate of change -0.34 cm 3 /y; p = 0.035), particularly in the temporal lobe. However, there was no association between sHHV and changes in total brain, total gray matter, or AD signature region volumes. Among the 119 participants with sHHV, exposure to antiviral treatment attenuated declines in occipital white matter ( p = 0.04). Although the sHHV group had higher cognitive scores at baseline, sHHV diagnosis was associated with accelerated longitudinal declines in attention (annual additional rate of change -0.01 Z-score/year; p = 0.008). In addition, sHHV diagnosis was associated with elevated plasma GFAP, but not related to Aβ 42/40 and NfL levels. Discussion These findings suggest an association of sHHV infection with white matter volume loss, attentional decline, and astrogliosis. Although the findings link sHHV to several neurocognitive features, the results do not support an association between sHHV and AD-specific disease processes.
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APA 7th
Duggan, M. R., Peng, Z., An, Y., Kitner Triolo, M. H., Shafer, A. T., Davatzikos, C., et al. (2022). Herpes Viruses in the Baltimore Longitudinal Study of Aging: Associations With Brain Volumes, Cognitive Performance, and Plasma Biomarkers. Neurology. https://doi.org/10.1212/wnl.0000000000201036
Vancouver
Duggan MR, Peng Z, An Y, Kitner Triolo MH, Shafer AT, Davatzikos C, et al. Herpes Viruses in the Baltimore Longitudinal Study of Aging: Associations With Brain Volumes, Cognitive Performance, and Plasma Biomarkers. Neurology. 2022. doi:10.1212/wnl.0000000000201036. PMID: 35985823.
BibTeX
@article{duggan2022-35985823,
author = {Duggan, M. R. and Peng, Z. and An, Y. and Kitner Triolo, M. H. and Shafer, A. T. and Davatzikos, C. and Erus, G. and Karikkineth, A. and others},
title = {{Herpes Viruses in the Baltimore Longitudinal Study of Aging: Associations With Brain Volumes, Cognitive Performance, and Plasma Biomarkers}},
journal = {Neurology},
year = {2022},
doi = {10.1212/wnl.0000000000201036},
pmid = {35985823},
url = {https://doi.org/10.1212/wnl.0000000000201036}
}
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Key findings
- Results A total of 1,009 participants were included in the primary MRI analysis, 98% of whom were cognitively normal at baseline MRI (mean age = 65.7 years; 54.8% female).
- Having a sHHV diagnosis (N = 119) was associated with longitudinal reductions in white matter volume (annual additional rate of change -0.34 cm 3 /y; p = 0.035), particularly in the temporal lobe.
- Although the sHHV group had higher cognitive scores at baseline, sHHV diagnosis was associated with accelerated longitudinal declines in attention (annual additional rate of change -0.01 Z-score/year; p = 0.008).
- In addition, sHHV diagnosis was associated with elevated plasma GFAP, but not related to Aβ 42/40 and NfL levels.
- Discussion These findings suggest an association of sHHV infection with white matter volume loss, attentional decline, and astrogliosis.
Why it matters
In 1,009 mostly cognitively normal older adults, having a symptomatic herpes virus diagnosis was linked to greater loss of white matter volume over time and to faster cognitive decline. This is an observational cohort study and does not show that treating or preventing herpes viruses would treat, cure or prevent Alzheimer's disease.
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Study details
- Study designcross-sectional
- Participants119
- Effect size54.8%
- Evidence strengthModerate
How this study scored 59/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2022 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 119 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 3 / 7 | Cited 23 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 3.8 citations a year over 6 year(s) since 2022 |
| Impact for its field and year | 2 / 6 | Cited 2.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 2 / 4 | Cited 19 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Keenan A. Walker: h-index 41 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 35985823) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 59 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000201036
- PubMed: 35985823
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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