title: Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia: A Population-Based Study.
abstract: OBJECTIVE
  Cerebral vasoreactivity (CVR) is a key factor in maintenance of continuous cerebral perfusion and a marker of (micro)vascular damage. We aimed to determine the longitudinal relation between CVR and the risk of dementia in the general population.
  
  
  RESULTS
  We determined CVR in nondemented participants who underwent transcranial Doppler with induced hypercapnia from 1997 to 1999, as part of the ongoing population-based Rotterdam Study. We used a Cox model to determine the risk of dementia in relation to CVR, adjusted for age, sex, cardiovascular risk factors, and carotid intima-media thickness. We furthermore determined decline on a cognitive test battery in relation to CVR, using linear mixed models. Among 1629 participants (mean ± SD age 70.6 ± 6.2 years, 46.2% female) with a mean follow-up of 11.5 years, 209 were diagnosed with dementia, of whom 171 had Alzheimer disease. Higher CVR at baseline was associated with lower risk of dementia (adjusted hazard ratio, 95% confidence interval, per SD increase: 0.87, 0.75-1.00) and Alzheimer disease (adjusted hazard ratio, 0.84; 0.71-0.99). This association was more profound in APOEε4 carriers than in noncarriers (adjusted hazard ratio for all dementia: 0.77, 0.60-0.98 versus 0.89, 0.73-1.07). Performance on cognitive tests at baseline was better with higher CVR (g-factor: P=0.02), but during 3 cognitive assessments over 11 years of follow-up, higher CVR at baseline was associated with less decline in test scores on the Stroop reading and interference tasks in APOEε4 carriers only (P=0.01 and 0.02, respectively).
  
  
  CONCLUSIONS
  Impaired CVR is associated with an increased risk of dementia in the general population.
authors.affiliation: From the Departments of Neurology (F.J.W., R.F.A.G.d.B., P.J.K., M.A.I.), Epidemiology (F.J.W., R.F.A.G.d.B., A.H., M.A.I.), and Radiology (M.A.I.), Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Wolters
authors.affiliation: From the Departments of Neurology (F.J.W., R.F.A.G.d.B., P.J.K., M.A.I.), Epidemiology (F.J.W., R.F.A.G.d.B., A.H., M.A.I.), and Radiology (M.A.I.), Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Renée F A G
authors.initials: RF
authors.lastname: de Bruijn
authors.affiliation: From the Departments of Neurology (F.J.W., R.F.A.G.d.B., P.J.K., M.A.I.), Epidemiology (F.J.W., R.F.A.G.d.B., A.H., M.A.I.), and Radiology (M.A.I.), Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: From the Departments of Neurology (F.J.W., R.F.A.G.d.B., P.J.K., M.A.I.), Epidemiology (F.J.W., R.F.A.G.d.B., A.H., M.A.I.), and Radiology (M.A.I.), Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.affiliation: From the Departments of Neurology (F.J.W., R.F.A.G.d.B., P.J.K., M.A.I.), Epidemiology (F.J.W., R.F.A.G.d.B., A.H., M.A.I.), and Radiology (M.A.I.), Erasmus Medical Centre, Rotterdam, The Netherlands. m.a.ikram@erasmusmc.nl.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
mesh_terms: D000368:Aged; D053327:Apolipoprotein E4 / Q000235:genetics*; D002560:Cerebrovascular Circulation; D003071:Cognition; D003704:Dementia / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D016016:Proportional Hazards Models; D012307:Risk Factors; D057190:Stroop Test; D013997:Time Factors; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D053327:Apolipoprotein E4; D005819:Genetic Markers
keywords: Alzheimer disease; apolipoprotein E; dementia; epidemiology; hypercapnia; vasoreactivity