title: Influence of multiple APOE genetic variants on cognitive function in a cohort of older men - results from the Normative Aging Study.
abstract: BACKGROUND
  APOE is the biomarker with the greatest known influence on cognitive function; however, the effect of complex haplotypes involving polymorphisms rs449647, rs405509, rs440446, rs429358 and rs7412 has never been studied in older populations.
  
  
  METHODS
  We evaluated APOE polymorphisms using multiplex PCR for genotyping and Mini-Mental State Examination (MMSE) to evaluate cognitive function in 819 individuals from VA Normative Aging Study.
  
  
  RESULTS
  Combinatorial analysis of all polymorphisms and individual analysis of polymorphisms rs449647, rs405509, rs440446 and rs7412 did not show any association with cognitive performance. Polymorphism rs429358 was associated with better cognitive performance (odds of MMSE ≤ 25 = 0.63, 95% CI 0.42-0.95; p = 0.03) in the oldest subsample (5th quintile of age) (odds of MMSE ≤ 25 = 0.34; 95% CI 0.13-0.86; p = 0.02). APOE allele ε4 was also associated with better cognitive performance (odds of MMSE ≤ 25 = 0.61, 95% CI 0.40-0.94; p = 0.02), also in the oldest subsample (odds of MMSE ≤ 25 = 0.35, 95% CI 0.14-0.90; p = 0.03).
  
  
  CONCLUSIONS
  These results suggest a beneficial effect of polymorphism rs429358 in the oldest men.
authors.forename: Diddier
authors.initials: D
authors.lastname: Prada
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.forename: Melinda C
authors.initials: MC
authors.lastname: Power
authors.forename: David G
authors.initials: DG
authors.lastname: Cox
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Avron
authors.initials: A
authors.lastname: Spiro Iii
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.forename: Jia
authors.initials: J
authors.lastname: Zhong
authors.forename: Marco
authors.initials: M
authors.lastname: Sanchez-Guerra
authors.forename: Luis A
authors.initials: LA
authors.lastname: Herrera
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, 665 Huntington Ave, Boston 02115, MA, USA. abaccare@hsph.harvard.edu.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000523:psychology*; D001057:Apolipoproteins E / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D001057:Apolipoproteins E
references.citation: J Geriatr Psychiatry Neurol. 2010 Jun;23(2):94-9
references.pmid: 20101070
references.citation: Alzheimers Dement. 2013 Mar;9(2):208-45
references.pmid: 23507120
references.citation: JAMA. 1998 Mar 11;279(10):751-5
references.pmid: 9508150
references.citation: Epidemiology. 2003 Nov;14(6):713-8
references.pmid: 14569188
references.citation: N Engl J Med. 2013 Apr 4;368(14):1326-34
references.pmid: 23550670
references.citation: JAMA Neurol. 2013 Apr;70(4):440-4
references.pmid: 23400708
references.citation: Am J Epidemiol. 2000 Apr 1;151(7):676-88
references.pmid: 10752795
references.citation: J Am Med Womens Assoc (1972). 1997 Summer;52(3):113-20
references.pmid: 9239999
references.citation: Neurology. 1999 Nov 10;53(8):1888-9
references.pmid: 10563653
references.citation: Eur J Hum Genet. 2009 Jul;17(7):938-45
references.pmid: 19172988
references.citation: Epidemiology. 2007 Jan;18(1):59-66
references.pmid: 17130688
references.citation: Dement Geriatr Cogn Disord. 2000 May-Jun;11(3):166-75
references.pmid: 10765048
references.citation: Alzheimers Dement. 2008 Jul;4(4):251-4
references.pmid: 18631975
references.citation: Neurosci Lett. 1996 Oct 25;218(1):9-12
references.pmid: 8939468
references.citation: AJNR Am J Neuroradiol. 2013 Dec;34(12):2287-93
references.pmid: 23828104
references.citation: Aging Cell. 2013 Apr;12(2):237-46
references.pmid: 23320904
references.citation: Neuroimage. 2013 Jan 15;65:364-73
references.pmid: 23063453
references.citation: Acta Neuropathol. 2010 Apr;119(4):421-33
references.pmid: 20204386
references.citation: Neurobiol Aging. 2010 May;31(5):787-95
references.pmid: 18606479
references.citation: FEBS Lett. 1998 Jan 9;421(2):105-8
references.pmid: 9468288
references.citation: Neurobiol Aging. 2014 Jul;35(7):1615-23
references.pmid: 24582638
references.citation: Atherosclerosis. 2005 Mar;179(1):161-7
references.pmid: 15721023
references.citation: Curr Alzheimer Res. 2006 Dec;3(5):411-9
references.pmid: 17168640
references.citation: Neuropsychology. 2005 Jan;19(1):28-34
references.pmid: 15656760
references.citation: Cogn Neurosci. 2013;4(3-4):136-42
references.pmid: 24168200
references.citation: JAMA. 1997 Oct 22-29;278(16):1349-56
references.pmid: 9343467
references.citation: Gerontologist. 1966 Dec;6(4):179-84
references.pmid: 5342911
references.citation: Trials. 2012 Nov 20;13:217
references.pmid: 23171483
references.citation: Hum Genet. 1984;65(3):237-41
references.pmid: 6698548
references.citation: J Am Geriatr Soc. 2003 Feb;51(2):178-83
references.pmid: 12558713
references.citation: Environ Health Perspect. 2011 May;119(5):682-7
references.pmid: 21172758
references.citation: Metabolism. 2011 May;60(5):655-63
references.pmid: 20723945
references.citation: Neurology. 1998 Sep;51(3):728-33
references.pmid: 9748017
references.citation: Environ Health. 2014 May 30;13(1):42
references.pmid: 24884505
references.citation: Bone. 2010 Sep;47(3):503-10
references.pmid: 20546958
references.citation: Hum Mol Genet. 1998 Nov;7(12):1887-92
references.pmid: 9811931
references.citation: Pediatr Res. 2010 Mar;67(3):293-9
references.pmid: 19952867
references.citation: J Neurol Neurosurg Psychiatry. 2007 Oct;78(10):1103-8
references.pmid: 17287237
references.citation: Neuropsychobiology. 2003;48(1):35-40
references.pmid: 12886039
references.citation: Cereb Cortex. 2007 Aug;17(8):1934-47
references.pmid: 17077159
references.citation: Neuropsychology. 2012 May;26(3):267-77
references.pmid: 22329498
references.citation: Hum Mol Genet. 2004 Nov 15;13(22):2885-92
references.pmid: 15385439
references.citation: Biol Psychol. 2007 Jul;75(3):229-38
references.pmid: 17433528
references.citation: Alzheimers Dement. 2013 Jan;9(1):12-8
references.pmid: 23123227
references.citation: Exp Gerontol. 2009 Mar;44(3):224-7
references.pmid: 19059330
references.citation: J Alzheimers Dis. 2011;24(2):235-45
references.pmid: 21263195
references.citation: J Am Geriatr Soc. 1992 Sep;40(9):922-35
references.pmid: 1512391
references.citation: J Alzheimers Dis. 2009;18(3):533-40
references.pmid: 19584451
references.citation: Neurology. 2001 Jul 10;57(1):89-95
references.pmid: 11445633
references.citation: Am J Geriatr Psychiatry. 2014 Oct;22(10):957-60
references.pmid: 24731780
references.citation: PLoS One. 2013;8(2):e57571
references.pmid: 23451244
references.citation: Neuropsychopharmacology. 2010 Apr;35(5):1090-6
references.pmid: 20072115