- Executive functioning
- WRAT-3 reading
Background/Aims: We hypothesized that inflammatory markers are cross-sectionally and longitudinally associated with neuropsychological indicators of early ischemia and Alzheimer’s disease. Methods: Framingham Offspring Study participants, free of clinical stroke or dementia (n = 1,878; 60 ± 9 years; 54% women), underwent neuropsychological assessment and ascertainment of 11 inflammatory markers. Follow-up neuropsychological assessments (6.3 ± 1.0 years) were conducted on 1,352 of the original 1,878 participants. Results: Multivariable linear regression related the inflammatory markers to cross-sectional performance and longitudinal change in neuropsychological performances. Secondary models included a twelfth factor, tumor necrosis factor-α (TNF-α), available on a subset of the sample (n = 1,393 cross-sectional; n = 1,213 longitudinal). Results suggest a few modest cross-sectional inflammatory and neuropsychological associations, particularly for tests assessing visual organization (C-reactive protein, p = 0.007), and a few modest relations between inflammatory markers and neuropsychological change, particularly for executive functioning (TNF-α, p = 0.004). Secondary analyses suggested that inflammatory markers were cross-sectionally (TNF-α, p = 0.004) related to reading performance. Conclusions: Our findings are largely negative, but suggest that specific inflammatory markers may have limited associations with poorer cognition and reading performance among community-dwelling adults. Because of multiple testing concerns, our limited positive findings are offered as hypothesis generating and require replication in other studies.
Copyright © 2011 S. Karger AG, Basel
- Yasojima K, Schwab C, McGeer EG, et al: Human neurons generate C-reactive protein and amyloid P: upregulation in Alzheimer’s disease. Brain Res 2000;887:80–89.
- Engelhart MJ, Geerlings MI, Meijer J, et al: Inflammatory proteins in plasma and the risk of dementia: The Rotterdam Study. Arch Neurol2004;61:668–672.
- McGeer EG, McGeer PL: Inflammatory processes in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:741–749.
- McGeer PL, McGeer EG: Inflammation, autotoxicity and Alzheimer disease. Neurobiol Aging 2001;22:799–809.
- Tarkowski E, Rosengren L, Blomstrand C, et al: Early intrathecal production of interleukin-6 predicts the size of brain lesion in stroke. Stroke 1995;26:1393–1398.
- Tarkowski E, Rosengren L, Blomstrand C, et al: Intrathecal release of pro- and anti-inflammatory cytokines during stroke. Clin Exp Immunol 1997;110:492–499.
- Weuve J, Ridker PM, Cook NR, et al: High-sensitivity C-reactive protein and cognitive function in older women. Epidemiology 2006;17:183–189.
- Dik MG, Jonker C, Hack CE, et al: Serum inflammatory proteins and cognitive decline in older persons. Neurology 2005;64:1371–1377.
- Schram MT, Euser SM, de Craen AJ, et al: Systemic markers of inflammation and cognitive decline in old age. J Am Geriatr Soc 2007;55:708–716.
- Yaffe K, Lindquist K, Penninx BW, et al: Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 2003;61:76–80.
- Weaver JD, Huang MH, Albert M, et al: Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology 2002;59:371–378.
- Wright CB, Sacco RL, Rundek TR, et al: Interleukin-6 is associated with cognitive function: the Northern Manhattan Study. J Stroke Cerebrovasc Dis2006;15:34–38.
- Rafnsson SB, Deary IJ, Smith FB, et al: Cognitive decline and markers of inflammation and hemostasis: the Edinburgh Artery Study. J Am Geriatr Soc 2007;55:700–707.
- Teunissen CE, van Boxtel MP, Bosma H, et al: Inflammation markers in relation to cognition in a healthy aging population. J Neuroimmunol 2003;134:142–150.
- Wolfe N, Linn R, Babikian VL, et al: Frontal systems impairment following multiple lacunar infarcts. Arch Neurol 1990;47:129–132.
- Cahn DA, Sullivan EV, Shear PK, et al: Structural MRI correlates of recognition memory in Alzheimer’s disease. J Int Neuropsychol Soc 1998;4:106–114.
- Zimmerman ME, Pan JW, Hetherington HP, et al: Hippocampal neurochemistry, neuromorphometry, and verbal memory in nondemented older adults. Neurology 2008;70:1594–1600.
- Kannel WB, Feinleib M, McNamara PM, et al: An investigation of coronary heart disease in families. The Framingham offspring study. Am J Epidemiol 1979;110:281–290.
- Cupples L, D’Agostino R: Some risk factors related to the annual incidence of cardiovascular disease and death using pooled repeated biennial measurements: Framingham Study, 30-year follow-up; in Kannel W, Polf P, Garrison R (eds): The Framingham Study: An Epidemiological Investigation of Cardiovascular Disease. Washington, National Institutes of Health, 1987, pp 87–203.
- Au R, Seshadri S, Wolf PA, et al: New norms for a new generation: cognitive performance in the Framingham offspring cohort. Exp Aging Res 2004;30:333–358.
- Schnabel R, Larson MG, Dupuis J, et al: Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection. Hypertension 2008;51:1651–1657.
- Kathiresan S, Larson MG, Vasan RS, et al: Contribution of clinical correlates and 13 C-reactive protein gene polymorphisms to inter-individual variability in serum C-reactive protein level. Circulation 2006;113:1415–1423.
- Jefferson AL, Himali J, Beiser A, et al: Cardiac index is associated with brain aging: The Framingham Heart Study. Circulation 2010;122:690–697.
- Jefferson AL, Massaro JM, Larson MG, et al: Inflammatory biomarkers are associated with total brain volume: The Framingham Heart Study. Neurology 2007;68:1032–1038.
- Hedges L, Laine R, Greenwald R: Does money matter? A meta-analysis of studies of the effects of differential school inputs on student outcomes. Educ Res1994;23:5–14.
- Manly JJ, Byrd DA, Touradji P, et al: Acculturation, reading level, and neuropsychological test performance among African American elders. Appl Neuropsychol2004;11:37–46.
- Manly JJ, Jacobs DM, Touradji P, et al: Reading level attenuates differences in neuropsychological test performance between African American and White elders. J Int Neuropsychol Soc 2002;8:341–348.
- Stern Y: What is cognitive reserve? Theory and research application of the reserve concept. J Int Neuropsychol Soc 2002;8:448–460.
- Manly JJ, Touradji P, Tang MX, et al: Literacy and memory decline among ethnically diverse elders. J Clin Exp Neuropsychol 2003;25:680–690.
- Dupuis J, Larson MG, Vasan RS, et al: Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: evidence for susceptibility loci on 1q. Atherosclerosis 2005;182:307–314.
- Jeerakathil T, Wolf PA, Beiser A, et al: Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study. Stroke 2004;35:1857–1861.
- Seshadri S, Wolf PA, Beiser A, et al: Stroke risk profile, brain volume, and cognitive function: the Framingham Offspring Study. Neurology 2004;63:1591–1599.
- Campbell IL, Abraham CR, Masliah E, et al: Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6. Proc Natl Acad Sci USA 1993;90:10061–10065.
- Libby P, Ridker PM, Maseri A: Inflammation and atherosclerosis. Circulation 2002;105:1135–1143.
- Reed BR, Eberling JL, Mungas D, et al: Memory failure has different mechanisms in subcortical stroke and Alzheimer’s disease. Ann Neurol 2000;48:275–284.
- Moritz CH, Johnson SC, McMillan KM, et al: Functional MRI neuroanatomic correlates of the Hooper Visual Organization Test. J Int Neuropsychol Soc 2004;10:939–947.
- Yochim B, Baldo J, Nelson A, et al: D-KEFS Trail Making Test performance in patients with lateral prefrontal cortex lesions. J Int Neuropsychol Soc 2007;13:704–709.
- Warner MH, Ernst J, Townes BD, et al: Relationships between IQ and neuropsychological measures in neuropsychiatric populations: within-laboratory and cross-cultural replications using WAIS and WAIS-R. J Clin Exp Neuropsychol 1987;9:545–562.
- Loucks EB, Sullivan LM, Hayes LJ, et al: Association of educational level with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol 2006;163:622–628.
- Lubbock LA, Goh A, Ali S, et al: Relation of low socioeconomic status to C-reactive protein in patients with coronary heart disease (from The Heart and Soul Study). Am J Cardiol 2005;96:1506–1511.
- Panagiotakos DB, Pitsavos CE, Chrysohoou CA, et al: The association between educational status and risk factors related to cardiovascular disease in healthy individuals: the ATTICA study. Ann Epidemiol 2004;14:188–194.
- Diez-Roux AV, Nieto FJ, Muntaner C, et al: Neighborhood environments and coronary heart disease: a multilevel analysis. Am J Epidemiol 1997;146:48–63.
- Smith GD, Hart C, Watt G, et al: Individual social class, area-based deprivation, cardiovascular disease risk factors, and mortality: the Renfrew and Paisley Study. J Epidemiol Commun Health 1998;52:399–405.
- Dimopoulos N, Piperi C, Salonicioti A, et al: Indices of low-grade chronic inflammation correlate with early cognitive deterioration in an elderly Greek population. Neurosci Lett 2006;398:118–123.
- Wechsler D: A standardized memory scale for clinical use. J Psychol1945;19:87–95.
- Reitan RM: Validity of the Trail Making Test as an indicator of organic brain damage. Percept Motor Skills 1958;8:271–276.
- Kaplan E, Goodglass H, Weintraub S: The Boston Naming Test, ed 2. Philadelphia, Lea & Febiger, 1983.
- Hooper H: Hooper Visual Organization Test (HVOT). Los Angeles, Western Psychological Services, 1983.
- Wechsler D: Wechsler Adult Intelligence Scale – Revised Manual. New York, Psychological Corporation, 1981.
Angela L. Jefferson, PhD
Alzheimer’s Disease Center, Boston University School of Medicine
72 East Concord Street, B-7800
Boston, MA 02118 (USA)
Tel. +1 617 414 1129, E-Mail email@example.com
Received: February 16, 2011
Accepted: April 21, 2011
Published online: July 13, 2011
Number of Print Pages : 10
Number of Figures : 1, Number of Tables : 5, Number of References : 49
Vol. 37, No. 1, Year 2011 (Cover Date: September 2011)
Journal Editor: Feigin V.L. (Auckland)
ISSN: 0251-5350 (Print), eISSN: 1423-0208 (Online)
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