title: Cross-sectional and longitudinal relationships between cerebrospinal fluid biomarkers and cognitive function in people without cognitive impairment from across the adult life span.
abstract: OBJECTIVE
  Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury.
  
  
  OBJECTIVE
  To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait.
  
  
  METHODS
  Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years.
  
  
  METHODS
  To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F2-isoprostanes (measures of free radical injury).
  
  
  RESULTS
  Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F2-isoprostane concentration was significantly associated with poorer executive function (adjusted R2 ≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal R2 ≤0.31).
  
  
  CONCLUSIONS
  Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.
authors.affiliation: School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.affiliation: Veterans Affairs (VA) Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Millard
authors.affiliation: School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle2Veterans Affairs (VA) Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington.
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicine, School of Medicine, University of Washington, Seattle5Geriatric Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington.
authors.forename: Chang-En
authors.initials: CE
authors.lastname: Yu
authors.affiliation: School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle6Department of Neurology, School of Medicine, University of Washington, Seattle.
authors.forename: James B
authors.initials: JB
authors.lastname: Leverenz
authors.affiliation: Veterans Affairs (VA) Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Mayer
authors.affiliation: School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Shofer
authors.affiliation: School of Medicine, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle2Veterans Affairs (VA) Northwest Network Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington.
authors.forename: Murray A
authors.initials: MA
authors.lastname: Raskind
authors.affiliation: Department of Neurology, School of Medicine, Oregon Health and Science University, Portland8VA Parkinson's Disease Research, Education, and Clinical Centers, Portland, Oregon.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.affiliation: School of Medicine, Department of Neurosciences, University of California, San Diego, La Jolla.
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Galasko
authors.affiliation: Department of Pathology, School of Medicine, University of Washington, Seattle.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003072:Cognition Disorders / Q000175:diagnosis* / Q000209:etiology / Q000523:psychology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins
references.citation: Cereb Cortex. 2012 Sep;22(9):1993-2004
references.pmid: 22038908
references.citation: Stroke. 2011 Aug;42(8):2326-9
references.pmid: 21700941
references.citation: Alzheimers Dement. 2011 Jul;7(4):386-395.e6
references.pmid: 21784349
references.citation: Neurobiol Aging. 2009 May;30(5):682-90
references.pmid: 17889968
references.citation: Alzheimer Dis Assoc Disord. 2005 Oct-Dec;19(4):220-5
references.pmid: 16327349
references.citation: Lancet Neurol. 2013 Oct;12(10):957-65
references.pmid: 24012374
references.citation: Neurology. 2010 Jul 13;75(2):160-7
references.pmid: 20625169
references.citation: Stat Med. 2000 Jun 15-30;19(11-12):1617-29
references.pmid: 10844723
references.citation: J Alzheimers Dis. 2013;36(3):563-70
references.pmid: 23629585
references.citation: N Engl J Med. 2012 Aug 30;367(9):795-804
references.pmid: 22784036
references.citation: JAMA Neurol. 2013 Aug;70(8):1039-45
references.pmid: 23779022
references.citation: Alzheimers Dement. 2013 Jul;9(4):406-13
references.pmid: 23141384
references.citation: Arch Neurol. 2011 Sep;68(9):1145-51
references.pmid: 21911695
references.citation: Free Radic Biol Med. 2008 Aug 1;45(3):219-30
references.pmid: 18482592
references.citation: Behav Neurol. 2009;21(1):117-28
references.pmid: 19847050
references.citation: J Lipid Res. 1990 Mar;31(3):545-8
references.pmid: 2341813
references.citation: Lancet Neurol. 2012 Dec;11(12):1048-56
references.pmid: 23137948
references.citation: Behav Brain Res. 1997 Aug;87(1):25-34
references.pmid: 9331471
references.citation: Curr Alzheimer Res. 2012 Jul;9(6):718-23
references.pmid: 22471861
references.citation: Neurology. 2007 Aug 14;69(7):631-9
references.pmid: 17698783
references.citation: Curr Alzheimer Res. 2011 Jun;8(4):336-40
references.pmid: 21222592
references.citation: Arch Neurol. 2011 Jun;68(6):743-52
references.pmid: 21670398
references.citation: Arch Neurol. 2010 Feb;67(2):217-23
references.pmid: 20142530
references.citation: Ann Neurol. 2009 Apr;65(4):403-13
references.pmid: 19296504
references.citation: Neuron. 2004 Sep 30;44(1):195-208
references.pmid: 15450170
references.citation: Neurology. 2012 Sep 25;79(13):1349-55
references.pmid: 22972646
references.citation: Neurology. 2013 Mar 26;80(13):1194-201
references.pmid: 23486873
references.citation: J Neurol Sci. 2011 Aug 15;307(1-2):100-5
references.pmid: 21621224
references.citation: Arch Clin Neuropsychol. 2006 Dec;21(8):771-5
references.pmid: 17011743
references.citation: J Alzheimers Dis. 2011;26(1):135-42
references.pmid: 21593572
references.citation: Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):291-4
references.pmid: 19812473
references.citation: Curr Alzheimer Res. 2012 Jul;9(6):664-72
references.pmid: 22471866
references.citation: Neurology. 2013 May 7;80(19):1784-91
references.pmid: 23576620
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Nov 15;827(1):88-93
references.pmid: 16260380
references.citation: J Alzheimers Dis. 2013;34(4):949-56
references.pmid: 23313924
references.citation: Arch Neurol. 2007 Mar;64(3):343-9
references.pmid: 17210801
references.citation: Neurology. 2013 Mar 19;80(12):1124-32
references.pmid: 23446677