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Cited by 150Dementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration MechanismsTryptophan and brain disorders

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study

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Walker, Keenan A., Hoogeveen, Ron C., Folsom, Aaron R., Ballantyne, Christie M., Knopman, David S., Windham, B. Gwen, Jack, Clifford R., Gottesman, Rebecca F.·2017·Neurology
DOI 10.1212/wnl.0000000000004688PMC PMC5705246
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Abstract

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 mm3 greater ventricular (p = 0.013), 110 mm3 smaller hippocampal (p = 0.013), 519 mm3 smaller occipital (p = 0.009), and 532 mm3 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.

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Metadata

Authors
Walker, K. A., Hoogeveen, R. C., Folsom, A. R., Ballantyne, C. M., Knopman, D. S., Windham, B. G., Jack, C. R., & Gottesman, R. F.
Affiliations
Houston Methodist (US)
ORCID
Venue
Neurology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2017-11-28
Volume
89
Issue
22
Pages
2262-2270
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
DOI
10.1212/wnl.0000000000004688
PMC
PMC5705246
OpenAlex
W2767064326
Cited by
150
References
6
Citations by year
2026: 20 · 2025: 14 · 2024: 22 · 2023: 19 · 2022: 13 · 2021: 10 · 2020: 15 · 2019: 15 · 2018: 22
FWCI
11.68
Type
journal article
Language
en
Update notices
correction (2023-08-21)
Open access
Locations
  • Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5u01hl096899-08, 5u01hl096902-08)
  • National Institute on Aging (K24AG052573, T32AG027668)
  • National Heart, Lung, and Blood Institute (U01HL096814, U01-HL-096899, U01-HL-096902, U01HL096917, U01HL096812)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
systemic inflammation, brain volume, hippocampal volume, ventriculomegaly, episodic memory, neurodegeneration, cognitive aging, fibrinogen, von Willebrand factor, factor VIII, white blood cell count, albumin, racial differences, age differences
MeSH terms
Age Factors, Aged, Black or African American, Brain, Factor VIII, Female, Fibrinogen, Humans, Inflammation, Leukocyte Count, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Residence Characteristics, Risk Factors, Sex Factors, von Willebrand Factor, Neurodegenerative Diseases, White People, Atherosclerosis, Memory, Episodic

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