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Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study
Walker KA, Hoogeveen RC, Folsom AR, Ballantyne CM, Knopman DS, Windham BG, Jack CR, Gottesman RF.. Neurology, 2017-11-01
Topic: Brain proteins, microglia and lab models
Objective To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late life using a large biracial prospective cohort study. Methods Plasma levels of systemic inflammatory markers (fibrinogen, albumin, white blood cell count, von Willebrand factor, and Factor VIII) were assessed at baseline in 1,633 participants (mean age 53 [5] years, 60% female, 27% African American) enrolled in the Atherosclerosis Risk in Communities Study. Using all 5 inflammatory markers, an inflammation composite score was created for each participant. We assessed episodic memory and regional brain volumes, using 3T MRI, 24 years later. Results Each SD increase in midlife inflammation composite score was associated with 1,788 mm 3 greater ventricular ( p = 0.013), 110 mm 3 smaller hippocampal ( p = 0.013), 519 mm 3 smaller occipital ( p = 0.009), and 532 mm 3 smaller Alzheimer disease signature region ( p = 0.008) volumes, and reduced episodic memory ( p = 0.046) 24 years later. Compared to participants with no elevated (4th quartile) midlife inflammatory markers, participants with elevations in 3 or more markers had, on average, 5% smaller hippocampal and Alzheimer disease signature region volumes. The association between midlife inflammation and late-life brain volume was modified by age and race, whereby younger participants and white participants with higher levels of systemic inflammation during midlife were more likely to show reduced brain volumes subsequently. Conclusions Our prospective findings provide evidence for what may be an early contributory role of systemic inflammation in neurodegeneration and cognitive aging.
Key findings
- Objective To clarify the temporal relationship between systemic inflammation and neurodegeneration, we examined whether a higher level of circulating inflammatory markers during midlife was associated with smaller brain volumes in late life using a large biracial prospective cohort study.
- Results Each SD increase in midlife inflammation composite score was associated with 1,788 mm 3 greater ventricular ( p = 0.013), 110 mm 3 smaller hippocampal ( p = 0.013), 519 mm 3 smaller occipital ( p = 0.009), and 532 mm 3 smaller Alzheimer disease signature region ( p = 0.008) volumes, and reduced episodic memory ( p = 0.046) 24 years later.
- Compared to participants with no elevated (4th quartile) midlife inflammatory markers, participants with elevations in 3 or more markers had, on average, 5% smaller hippocampal and Alzheimer disease signature region volumes.
Why it matters
In this cohort, higher midlife levels of circulating inflammatory markers were associated with smaller brain volumes and reduced episodic memory 24 years later. This links midlife systemic inflammation to later brain structure and memory, but does not show that treating inflammation prevents Alzheimer's disease.
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Study details
- Study designcohort study
- Participants1,633
- Evidence strengthModerate
How this study scored 68/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for effect reported and 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 | 7 / 12 | A cohort study following people over 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 | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,633 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | 5 / 7 | Cited 148 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.5 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 10 other studies in this library |
| Still being cited | 3 / 4 | Cited 54 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Rebecca F. Gottesman: h-index 92 (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 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29093073) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 68 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000004688
- PubMed: 29093073
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Walker, K. A., Hoogeveen, R. C., Folsom, A. R., Ballantyne, C. M., Knopman, D. S., Windham, B. G., et al. (2017). Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study. Neurology. https://doi.org/10.1212/wnl.0000000000004688
Vancouver
Walker KA, Hoogeveen RC, Folsom AR, Ballantyne CM, Knopman DS, Windham BG, et al. Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study. Neurology. 2017. doi:10.1212/wnl.0000000000004688. PMID: 29093073.
BibTeX
@article{walker2017-29093073,
author = {Walker, K. A. and Hoogeveen, R. C. and Folsom, A. R. and Ballantyne, C. M. and Knopman, D. S. and Windham, B. G. and Jack, C. R. and Gottesman, R. F.},
title = {{Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study}},
journal = {Neurology},
year = {2017},
doi = {10.1212/wnl.0000000000004688},
pmid = {29093073},
url = {https://doi.org/10.1212/wnl.0000000000004688}
}
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