Keenan A Walker1, Ron C Hoogeveen2, Aaron R Folsom2, Christie M Ballantyne2, David S Knopman2, B Gwen Windham2, Clifford R Jack2, Rebecca F Gottesman2. 1. From the Departments of Neurology (K.A.W., R.F.G.) and Epidemiology (R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Section of Cardiology (R.C.H., C.M.B.), Baylor College of Medicine; Center for Cardiovascular Disease Prevention (R.C.H., C.M.B.), Houston Methodist DeBakey Heart and Vascular Center, TX; Division of Epidemiology and Community Health (A.R.F.), School of Public Health, University of Minnesota, Minneapolis; Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; and Department of Medicine (B.G.W.), University of Mississippi Medical Center, Jackson. Kwalke26@jhmi.edu. 2. From the Departments of Neurology (K.A.W., R.F.G.) and Epidemiology (R.F.G.), Johns Hopkins University School of Medicine, Baltimore, MD; Section of Cardiology (R.C.H., C.M.B.), Baylor College of Medicine; Center for Cardiovascular Disease Prevention (R.C.H., C.M.B.), Houston Methodist DeBakey Heart and Vascular Center, TX; Division of Epidemiology and Community Health (A.R.F.), School of Public Health, University of Minnesota, Minneapolis; Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; and Department of Medicine (B.G.W.), University of Mississippi Medical Center, Jackson.
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.
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.
Authors: Robert C Green; L Adrienne Cupples; Rodney Go; Kelly S Benke; Timi Edeki; Patrick A Griffith; Mary Williams; Yvonne Hipps; Neill Graff-Radford; David Bachman; Lindsay A Farrer Journal: JAMA Date: 2002-01-16 Impact factor: 56.272
Authors: Bruce Fischl; David H Salat; Evelina Busa; Marilyn Albert; Megan Dieterich; Christian Haselgrove; Andre van der Kouwe; Ron Killiany; David Kennedy; Shuna Klaveness; Albert Montillo; Nikos Makris; Bruce Rosen; Anders M Dale Journal: Neuron Date: 2002-01-31 Impact factor: 17.173
Authors: Mike F Schmidt; Kevin B Freeman; Beverly G Windham; Michael E Griswold; Iftikhar J Kullo; Stephen T Turner; Thomas H Mosley Journal: J Am Geriatr Soc Date: 2016-08-22 Impact factor: 5.562
Authors: Rebecca F Gottesman; Andreea M Rawlings; A Richey Sharrett; Marilyn Albert; Alvaro Alonso; Karen Bandeen-Roche; Laura H Coker; Josef Coresh; David J Couper; Michael E Griswold; Gerardo Heiss; David S Knopman; Mehul D Patel; Alan D Penman; Melinda C Power; Ola A Selnes; Andrea L C Schneider; Lynne E Wagenknecht; B Gwen Windham; Lisa M Wruck; Thomas H Mosley Journal: Am J Epidemiol Date: 2014-03-13 Impact factor: 4.897
Authors: Thais Minett; John Classey; Fiona E Matthews; Marie Fahrenhold; Mariko Taga; Carol Brayne; Paul G Ince; James A R Nicoll; Delphine Boche Journal: J Neuroinflammation Date: 2016-06-02 Impact factor: 8.322
Authors: Keenan A Walker; B Gwen Windham; Charles H Brown; David S Knopman; Clifford R Jack; Thomas H Mosley; Elizabeth Selvin; Dean F Wong; Timothy M Hughes; Yun Zhou; Alden L Gross; Rebecca F Gottesman Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472
Authors: Eli P Darnell; Kristen E Wroblewski; Kristina L Pagel; David W Kern; Martha K McClintock; Jayant M Pinto Journal: Chem Senses Date: 2020-05-29 Impact factor: 3.160
Authors: E Lydia Wu-Chung; Stephanie L Leal; Bryan T Denny; Samantha L Cheng; Christopher P Fagundes Journal: Neurosci Biobehav Rev Date: 2021-12-29 Impact factor: 8.989
Authors: V Alexandra Moser; Amy Christensen; Jiahui Liu; Amanda Zhou; Shunya Yagi; Christopher R Beam; Liisa Galea; Christian J Pike Journal: Neurobiol Aging Date: 2018-09-22 Impact factor: 4.673
Authors: Keenan A Walker; Rebecca F Gottesman; Aozhou Wu; David S Knopman; Thomas H Mosley; Alvaro Alonso; Anna Kucharska-Newton; Charles H Brown Journal: J Am Geriatr Soc Date: 2018-09-24 Impact factor: 5.562
Authors: Alexandra M V Wennberg; Clinton E Hagen; Mary M Machulda; David S Knopman; Ronald C Petersen; Michelle M Mielke Journal: J Gerontol A Biol Sci Med Sci Date: 2019-07-12 Impact factor: 6.053
Authors: Keenan A Walker; Rebecca F Gottesman; Aozhou Wu; David S Knopman; Alden L Gross; Thomas H Mosley; Elizabeth Selvin; B Gwen Windham Journal: Neurology Date: 2019-02-13 Impact factor: 9.910