title: Nonstroke cardiovascular disease and risk of Alzheimer disease and dementia.
abstract: Unresolved issues in dementia research include (1) the association between nonstroke cardiovascular disease (CVD) and Alzheimer disease (AD) and (2) whether the association between CVD and dementia is mediated by familial factors (ie, genes and early life environment). We therefore conducted a study with both a longitudinal and a co-twin control design in 2214 Swedish twins with clinical dementia evaluation and apolipoprotein E (ApoE) genotyping. The analyses were then replicated in a register-based cohort of 18,405 individuals. Results show that CVD increases the risk of AD in carriers (but not noncarriers) of the ApoE4 allele (hazard ratio 2.39, 95% confidence interval 1.15-4.96). CVD was also associated with an almost 2-fold increased risk of developing late-life dementia (hazard ratio 1.83, 95% confidence interval 1.23-2.72). Within twin pairs, the dementia-affected twin was more likely to have had CVD than the nondemented twin partner (odds ratio 1.86, 95% confidence interval 1.11-3.13). In conclusion, this study shows that (1) nonstroke CVD increases the risk of late-life dementia but that it is only a risk factor for AD in carriers of the ApoE4 allele and (2) the association between CVD and dementia is not explained by genetic or early life environmental factors in common to both disorders.
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Ulrika.Eriksson@ki.se
authors.forename: Ulrika K
authors.initials: UK
authors.lastname: Eriksson
authors.forename: Anna M
authors.initials: AM
authors.lastname: Bennet
authors.forename: Margaret
authors.initials: M
authors.lastname: Gatz
authors.forename: Paul W
authors.initials: PW
authors.lastname: Dickman
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D015331:Cohort Studies; D004777:Environment; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012042:Registries; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D014427:Twins / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: JAMA. 1997 Oct 22-29;278(16):1349-56
references.pmid: 9343467
references.citation: J Intern Med. 2006 Sep;260(3):211-23
references.pmid: 16918818
references.citation: Lancet Neurol. 2007 Aug;6(8):734-46
references.pmid: 17616482
references.citation: Neurology. 2000 Jan 25;54(2):397-402
references.pmid: 10668701
references.citation: Lancet. 2004 Apr 3;363(9415):1139-46
references.pmid: 15064035
references.citation: J Gerontol A Biol Sci Med Sci. 1997 Mar;52(2):M117-25
references.pmid: 9060980
references.citation: Neurology. 1993 Feb;43(2):250-60
references.pmid: 8094895
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Neurology. 1999 Oct 22;53(7):1593-5
references.pmid: 10534277
references.citation: Ann Neurol. 2006 Dec;60(6):677-87
references.pmid: 17192928
references.citation: J Am Geriatr Soc. 2005 Jul;53(7):1101-7
references.pmid: 16108925
references.citation: Lancet. 1997 Jan 18;349(9046):151-4
references.pmid: 9111537
references.citation: Arch Intern Med. 2005 Feb 14;165(3):321-6
references.pmid: 15710796
references.citation: Lancet Neurol. 2005 Nov;4(11):752-9
references.pmid: 16239182
references.citation: Ann Neurol. 2007 May;61(5):403-10
references.pmid: 17328068
references.citation: J Intern Med. 2002 Sep;252(3):184-205
references.pmid: 12270000
references.citation: Behav Genet. 2003 Mar;33(2):95-105
references.pmid: 14574145
references.citation: Dement Geriatr Cogn Disord. 2008;25(2):148-56
references.pmid: 18097143
references.citation: JAMA. 2007 Sep 19;298(11):1300-11
references.pmid: 17878422
references.citation: BMJ. 1994 Jun 18;308(6944):1604-8
references.pmid: 8025427
references.citation: Neurology. 2004 Apr 13;62(7):1148-55
references.pmid: 15079015
references.citation: Circulation. 2009 Jan 27;119(3):e21-181
references.pmid: 19075105
references.citation: Nature. 2000 Sep 14;407(6801):233-41
references.pmid: 11001066
references.citation: Dement Geriatr Cogn Disord. 2006;22(3):244-9
references.pmid: 16902279
references.citation: Arch Intern Med. 2006 May 8;166(9):1003-8
references.pmid: 16682574
references.citation: Alzheimer Dis Assoc Disord. 2002 Oct-Dec;16(4):203-12
references.pmid: 12468894
references.citation: Science. 1997 Jun 6;276(5318):1560-3
references.pmid: 9171059
references.citation: J Gerontol B Psychol Sci Soc Sci. 2002 May;57(3):S168-76
references.pmid: 11983743
references.citation: Neurology. 2006 May 9;66(9):1399-404
references.pmid: 16682673
references.citation: Aging Clin Exp Res. 2007 Oct;19(5):381-9
references.pmid: 18007116
references.citation: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5644-51
references.pmid: 16567625
references.citation: Lancet. 2001 Jan 20;357(9251):169-75
references.pmid: 11213093
references.citation: Neurology. 2004 Aug 24;63(4):739-41
references.pmid: 15326258