The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study

Keenan A. Walker; B. Gwen Windham; Melinda C. Power; Ron C. Hoogeveen; Aaron R. Folsom; Christie M. Ballantyne; David S. Knopman; Elizabeth Selvin; Clifford R. Jack; Rebecca F. Gottesman

doi:10.1016/j.neurobiolaging.2018.03.031

The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study

Keenan A. Walker, B. Gwen Windham, Melinda C. Power, Ron C. Hoogeveen, Aaron R. Folsom, Christie M. Ballantyne, David S. Knopman, Elizabeth Selvin, Clifford R. Jack, Rebecca F. Gottesman

Epidemiology

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Abstract

We examined whether the pattern of middle- to late-life systemic inflammation was associated with white matter (WM) structural abnormalities in older adults. A total of 1532 participants (age = 76.5; standard deviations = 5.4) underwent 3T brain magnetic resonance imaging to quantify white matter hyperintensity volume and whole-brain WM microstructural integrity (fractional anisotropy, mean diffusivity). High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, was measured at 3 visits (21 and 14 years before, and concurrent with, neuroimaging). Participants were categorized into 1 of 6 groups based on their 21-year pattern of low (<3 mg/L) versus elevated (≥3 mg/L) CRP. Compared to the group with low CRP at all 3 visits, the group that transitioned from low to elevated CRP during midlife demonstrated greatest white matter hyperintensity volume and poorest WM microstructural integrity, after adjusting for demographic variables and cardiovascular risk factors. Participants with high CRP at all visits also demonstrated greater WM structural abnormalities, but only after accounting for differential attrition. These results suggest that increasing and persistent inflammation in the decades spanning middle-to late-life may promote WM disease in older adults.

Original language	English (US)
Pages (from-to)	26-33
Number of pages	8
Journal	Neurobiology of Aging
Volume	68
DOIs	https://doi.org/10.1016/j.neurobiolaging.2018.03.031
State	Published - Aug 2018

Bibliographical note

Funding Information:
The Atherosclerosis Risk in Communities study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Neurocognitive data is collected by U01 HL096812, HL096814, HL096899, HL096902, HL096917 from the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke, with previous brain MRI examinations funded by R01-HL70825 from the National Heart, Lung, and Blood Institute. This study was also supported by contracts T32 AG027668 (Dr. Walker) and K24 AG052573 (Dr. Gottesman) from the National Institute on Aging, and K24DK106414 and R01DK089174 (Dr. Selvin) from the National Institute of Diabetes and Digestive and Kidney Diseases. The sponsors had no role in the design and conduct of the study; collection management, analysis and interpretation of the data; or preparation review, or approval of the article. The authors thank the staff and participants of the ARIC study for their important contributions. Appendix A

Funding Information:
D.S.K. serves on a Data Safety Monitoring Board for the DIAN study, is an investigator in clinical trials sponsored by Lilly Pharmaceuticals, Biogen and the Alzheimer's Treatment and Research Institute at the University of Southern California and receives research support from the NIH. B.G.W. receives research support from NIH, is an investigator/dementia expert on a CMS Coverage with Evidence Development study and is an investigator in a clinical trial sponsored by ACADIA Pharmaceutical. C.R.J. serves on a scientific advisory board for Eli Lilly and Company and receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation. R.F.G. serves as associate editor for Neurology and receives research support from NIH. The other authors declare no competing interests.

Publisher Copyright:
© 2018

Keywords

Aging
Brain
Diffusion tensor imaging
Inflammation
Magnetic resonance imaging
White matter disease

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10.1016/j.neurobiolaging.2018.03.031

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010227

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Walker, K. A., Windham, B. G., Power, M. C., Hoogeveen, R. C., Folsom, A. R., Ballantyne, C. M., Knopman, D. S., Selvin, E., Jack, C. R., & Gottesman, R. F. (2018). The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study. Neurobiology of Aging, 68, 26-33. https://doi.org/10.1016/j.neurobiolaging.2018.03.031

Walker, KA, Windham, BG, Power, MC, Hoogeveen, RC, Folsom, AR, Ballantyne, CM, Knopman, DS, Selvin, E, Jack, CR & Gottesman, RF 2018, 'The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study', Neurobiology of Aging, vol. 68, pp. 26-33. https://doi.org/10.1016/j.neurobiolaging.2018.03.031

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abstract = "We examined whether the pattern of middle- to late-life systemic inflammation was associated with white matter (WM) structural abnormalities in older adults. A total of 1532 participants (age = 76.5; standard deviations = 5.4) underwent 3T brain magnetic resonance imaging to quantify white matter hyperintensity volume and whole-brain WM microstructural integrity (fractional anisotropy, mean diffusivity). High-sensitivity C-reactive protein (CRP), a marker of systemic inflammation, was measured at 3 visits (21 and 14 years before, and concurrent with, neuroimaging). Participants were categorized into 1 of 6 groups based on their 21-year pattern of low (<3 mg/L) versus elevated (≥3 mg/L) CRP. Compared to the group with low CRP at all 3 visits, the group that transitioned from low to elevated CRP during midlife demonstrated greatest white matter hyperintensity volume and poorest WM microstructural integrity, after adjusting for demographic variables and cardiovascular risk factors. Participants with high CRP at all visits also demonstrated greater WM structural abnormalities, but only after accounting for differential attrition. These results suggest that increasing and persistent inflammation in the decades spanning middle-to late-life may promote WM disease in older adults.",

keywords = "Aging, Brain, Diffusion tensor imaging, Inflammation, Magnetic resonance imaging, White matter disease",

author = "Walker, {Keenan A.} and Windham, {B. Gwen} and Power, {Melinda C.} and Hoogeveen, {Ron C.} and Folsom, {Aaron R.} and Ballantyne, {Christie M.} and Knopman, {David S.} and Elizabeth Selvin and Jack, {Clifford R.} and Gottesman, {Rebecca F.}",

note = "Funding Information: The Atherosclerosis Risk in Communities study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). Neurocognitive data is collected by U01 HL096812, HL096814, HL096899, HL096902, HL096917 from the National Heart, Lung, and Blood Institute and the National Institute of Neurological Disorders and Stroke, with previous brain MRI examinations funded by R01-HL70825 from the National Heart, Lung, and Blood Institute. This study was also supported by contracts T32 AG027668 (Dr. Walker) and K24 AG052573 (Dr. Gottesman) from the National Institute on Aging, and K24DK106414 and R01DK089174 (Dr. Selvin) from the National Institute of Diabetes and Digestive and Kidney Diseases. The sponsors had no role in the design and conduct of the study; collection management, analysis and interpretation of the data; or preparation review, or approval of the article. The authors thank the staff and participants of the ARIC study for their important contributions. Appendix A Funding Information: D.S.K. serves on a Data Safety Monitoring Board for the DIAN study, is an investigator in clinical trials sponsored by Lilly Pharmaceuticals, Biogen and the Alzheimer's Treatment and Research Institute at the University of Southern California and receives research support from the NIH. B.G.W. receives research support from NIH, is an investigator/dementia expert on a CMS Coverage with Evidence Development study and is an investigator in a clinical trial sponsored by ACADIA Pharmaceutical. C.R.J. serves on a scientific advisory board for Eli Lilly and Company and receives research support from NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation. R.F.G. serves as associate editor for Neurology and receives research support from NIH. The other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2018",

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AU - Power, Melinda C.

AU - Hoogeveen, Ron C.

AU - Folsom, Aaron R.

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AU - Knopman, David S.

AU - Selvin, Elizabeth

AU - Jack, Clifford R.

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The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study

Abstract

Bibliographical note

Keywords

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