title: Brain imaging and cognitive predictors of stroke and Alzheimer disease in the Framingham Heart Study.
abstract: OBJECTIVE
  Exposure to vascular risk factors has a gradual deleterious effect on brain MRI and cognitive measures. We explored whether a pattern of these measures exists that predicts stroke and Alzheimer disease (AD) risk.
  
  
  METHODS
  A cognitive battery was administered to 1679 dementia and stroke-free Framingham offspring (age, >55 years; mean, 65.7±7.0) between 1999 and 2004; participants were also free of other neurological conditions that could affect cognition and >90% also had brain MRI examination. We related cognitive and MRI measures to risks of incident stroke and AD ≤10 years of follow-up. As a secondary analysis, we explored these associations in The Framingham Heart Study original cohort (mean age, 67.5±7.3 and 84.8±3.3 years at the cognitive assessment and MRI examination, respectively).
  
  
  RESULTS
  A total of 55 Offspring participants sustained strokes and 31 developed AD. Offspring who scored <1.5 SD below predicted mean scores, for age and education, on an executive function test, had a higher risk of future stroke (hazard ratio [HR], 2.27; 95% confidence interval [CI], 1.06-4.85) and AD (HR, 3.60; 95% CI, 1.52-8.52); additional cognitive tests also predicted AD. Participants with low (<20 percentile) total brain volume and high (>20 percentile) white matter hyperintensity volume had a higher risk of stroke (HR, 1.97; 95% CI, 1.03-3.77 and HR, 2.74; 95% CI, 1.51-5.00, respectively) but not AD. Hippocampal volume at the bottom quintile predicted AD in the offspring and original cohorts (HR, 4.41; 95% CI, 2.00-9.72 and HR, 2.37; 95% CI, 1.12-5.00, respectively). A stepwise increase in stroke risk was apparent with increasing numbers of these cognitive and imaging markers.
  
  
  CONCLUSIONS
  Specific patterns of cognitive and brain structural measures observed even in early aging predict stroke risk and may serve as biomarkers for risk prediction.
authors.affiliation: From the Department of Neurology, Boston University School of Medicine, Boston, MA (G.W., A.S.B., R.A., P.A.W., S.S.); The Framingham Heart Study, Boston, MA (G.W., A.S.B., R.A., P.A.W., S.S.); Department of Biostatistics, Boston University School of Public Health, Boston, MA (A.S.B.); and the Department of Neurology, University of California at Davis, Sacramento, CA (C.D.).
authors.forename: Galit
authors.initials: G
authors.lastname: Weinstein
authors.forename: Alexa S
authors.initials: AS
authors.lastname: Beiser
authors.forename: Charles
authors.initials: C
authors.lastname: Decarli
authors.forename: Rhoda
authors.initials: R
authors.lastname: Au
authors.forename: Philip A
authors.initials: PA
authors.lastname: Wolf
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003071:Cognition; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000000981:diagnostic imaging*
keywords: Alzheimer disease; cognition; magnetic resonance imaging; stroke
references.citation: J Intern Med. 2004 Sep;256(3):183-94
references.pmid: 15324362
references.citation: J Int Neuropsychol Soc. 2008 Mar;14(2):266-78
references.pmid: 18282324
references.citation: Neurology. 2012 Nov 13;79(20):2029-36
references.pmid: 23115210
references.citation: Prev Med. 1975 Dec;4(4):518-25
references.pmid: 1208363
references.citation: Lancet. 2011 Mar 19;377(9770):1019-31
references.pmid: 21371747
references.citation: Stroke. 1994 Apr;25(4):802-7
references.pmid: 8160224
references.citation: Stroke. 2004 Nov;35(11 Suppl 1):2620-2
references.pmid: 15375299
references.citation: J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1174-9
references.pmid: 22917672
references.citation: Stroke. 2004 Aug;35(8):1857-61
references.pmid: 15218158
references.citation: Stroke. 1999 Mar;30(3):529-36
references.pmid: 10066847
references.citation: Radiology. 2011 Jun;259(3):844-51
references.pmid: 21467255
references.citation: Neurology. 2010 Feb 2;74(5):379-85
references.pmid: 20124202
references.citation: Alzheimers Dement. 2006 Jul;2(3):171-8
references.pmid: 19595880
references.citation: Neurology. 1997 May;48(5):1297-304
references.pmid: 9153461
references.citation: Neurology. 2004 Nov 9;63(9):1591-9
references.pmid: 15534241
references.citation: Neurobiol Aging. 2005 Apr;26(4):491-510
references.pmid: 15653178
references.citation: Circulation. 2010 Feb 23;121(7):e46-e215
references.pmid: 20019324
references.citation: Neurology. 2005 May 24;64(10):1704-11
references.pmid: 15911795
references.citation: Stroke. 1991 Mar;22(3):312-8
references.pmid: 2003301
references.citation: Neurology. 2011 May 31;76(22):1879-85
references.pmid: 21543737
references.citation: Neurology. 2005 Oct 25;65(8):1227-31
references.pmid: 16247049
references.citation: Am J Epidemiol. 2012 Sep 15;176(6):473-81
references.pmid: 22875755
references.citation: Neurology. 2005 May 24;64(10):1750-5
references.pmid: 15911803
references.citation: Arch Neurol. 2003 Oct;60(10):1385-9
references.pmid: 14568808
references.citation: Lancet Neurol. 2002 Nov;1(7):426-36
references.pmid: 12849365
references.citation: J Comput Assist Tomogr. 1992 Mar-Apr;16(2):274-84
references.pmid: 1545026
references.citation: Neurology. 1997 Dec;49(6):1498-504
references.pmid: 9409336
references.citation: Stroke. 2004 Feb;35(2):404-9
references.pmid: 14726556
references.citation: Stroke. 1994 Jan;25(1):40-3
references.pmid: 8266381
references.citation: Arch Neurol. 2006 Feb;63(2):246-50
references.pmid: 16476813
references.citation: Am J Geriatr Psychiatry. 2005 Feb;13(2):134-41
references.pmid: 15703322
references.citation: Stroke. 2010 Apr;41(4):600-6
references.pmid: 20167919
references.citation: BMJ. 2010 Jul 26;341:c3666
references.pmid: 20660506
references.citation: Neurobiol Aging. 2012 Apr;33(4):825.e25-36
references.pmid: 21782287
references.citation: Neurology. 2006 Aug 8;67(3):441-5
references.pmid: 16894105
references.citation: Neurology. 1984 Jul;34(7):939-44
references.pmid: 6610841
references.citation: Arch Neurol. 2008 May;65(5):642-9
references.pmid: 18474741
references.citation: J Intern Med. 2004 Sep;256(3):195-204
references.pmid: 15324363
references.citation: Lancet Neurol. 2010 Jan;9(1):119-28
references.pmid: 20083042
references.citation: Arch Neurol. 1998 Mar;55(3):395-401
references.pmid: 9520014
references.citation: Dement Geriatr Cogn Disord. 2010;29(2):164-75
references.pmid: 20150735
references.citation: Ann Neurol. 2005 Oct;58(4):610-6
references.pmid: 16178017
references.citation: Am J Public Health Nations Health. 1951 Mar;41(3):279-81
references.pmid: 14819398
references.citation: Lancet. 2005 Dec 17;366(9503):2112-7
references.pmid: 16360788
references.citation: Stroke. 2004 Jun;35(6):1264-8
references.pmid: 15118167
references.citation: Circulation. 2011 Feb 1;123(4):e18-e209
references.pmid: 21160056
references.citation: Psychol Rep. 1987 Jun;60(3 Pt 2):1023-40
references.pmid: 3628637
references.citation: Exp Aging Res. 2004 Oct-Dec;30(4):333-58
references.pmid: 15371099
references.citation: Neurology. 2007 Apr 17;68(16):1268-73
references.pmid: 17438217
references.citation: Arch Neurol. 2005 Nov;62(11):1739-46
references.pmid: 16286549
references.citation: Arch Neurol. 2000 Jun;57(6):808-13
references.pmid: 10867777